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Al-Beltagi M, Saeed NK, Bediwy AS, Elbeltagi R. Unraveling the nutritional challenges in epilepsy: Risks, deficiencies, and management strategies: A systematic review. World J Exp Med 2025; 15:104328. [DOI: 10.5493/wjem.v15.i2.104328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 02/24/2025] [Accepted: 03/18/2025] [Indexed: 04/16/2025] Open
Abstract
BACKGROUND Malnutrition and epilepsy share a complex bidirectional relationship, with malnutrition serving as a potential risk factor for epilepsy development, while epilepsy, in turn, often exerts profound effects on nutritional status. Nutritional interventions have emerged as a critical adjunctive approach in epilepsy management.
AIM To explore the multifaceted associations between malnutrition and epilepsy, structured into three primary sections: (1) Elucidating the impact of malnutrition as a risk factor for epilepsy onset; (2) Examining the reciprocal influence of epilepsy on nutritional status, and (3) Evaluating diverse nutritional interventions in the management of epilepsy.
METHODS A systematic search was conducted across PubMed, Scopus, and Web of Science databases utilizing defined keywords related to malnutrition, epilepsy, and nutritional interventions. Inclusion criteria encompassed various study types, including clinical trials, animal models, cohort studies, case reports, meta-analyses, systematic reviews, guidelines, editorials, and review articles. Four hundred sixteen pertinent references were identified, with 198 review articles, 153 research studies, 21 case reports, 24 meta-analyses, 14 systematic reviews, 4 guidelines, and 2 editorials meeting the predefined criteria.
RESULTS The review revealed the intricate interplay between malnutrition and epilepsy, highlighting malnutrition as a potential risk factor in epilepsy development and elucidating how epilepsy often leads to nutritional deficiencies. Findings underscored the importance of nutritional interventions in managing epilepsy, showing their impact on seizure frequency, neuronal function, and overall brain health.
CONCLUSION This systematic review emphasizes the bidirectional relationship between malnutrition and epilepsy while emphasizing the critical role of nutritional management in epilepsy treatment. The multifaceted insights underscore the need for a holistic approach to addressing nutritional aspects alongside conventional epilepsy management strategies.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Governmental Hospitals, Manama 12, Bahrain
- Medical Microbiology Section, Department of Pathology, The Royal College of Surgeons in Ireland, Busaiteen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Pulmonology, Faculty of Medicine, Tanta University, Tanta 31527, Alghrabia, Egypt
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| | - Reem Elbeltagi
- Medicine, Royal College of Surgeons in Ireland, Medical University of Bahrain, Busaiteen 15503, Muharraq, Bahrain
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Kandemirli SG, Al-Dasuqi K, Aslan B, Goldstein A, Alves CAPF. Overview of neuroimaging in primary mitochondrial disorders. Pediatr Radiol 2025; 55:765-791. [PMID: 39937244 DOI: 10.1007/s00247-025-06172-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 01/10/2025] [Accepted: 01/13/2025] [Indexed: 02/13/2025]
Abstract
Advancements in understanding the clinical, biochemical, and genetic aspects of primary mitochondrial disorders, along with the identification of a broad range of phenotypes frequently involving the central nervous system, have opened a new and crucial area in neuroimaging. This expanding knowledge presents significant challenges for radiologists in clinical settings, as the neuroimaging features and their associated metabolic abnormalities become more complex. This review offers a comprehensive overview of the key neuroimaging features associated with the common primary mitochondrial disorders. It highlights both the classical imaging findings and the emerging diagnostic insights related to several previously identified causative genes for these diseases. The review also provides an in-depth description of the clinicoradiologic presentations and potential underlying mitochondrial defects, aiming to enhance diagnostic abilities of radiologists in identifying primary mitochondrial diseases in their clinical practice.
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Affiliation(s)
- Sedat Giray Kandemirli
- Duke University Hospital, 2301 Erwin Rd, Durham, NC, 27710, USA.
- Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
| | - Khalid Al-Dasuqi
- Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA
- Sidra Medical and Research Center, Doha, Qatar
| | - Bulent Aslan
- Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Amy Goldstein
- Children's Hospital of Philadelphia, Philadelphia, PA, USA
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3
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Kitwan L, Makobe C, Mdachi R, Maranga DN, Isaac AO, Nyariki JN. Coenzyme Q 10 prevented Trypanosoma brucei rhodesiense-mediated breach of the blood brain barrier, inflammation and organ damage in late stage of Human African Trypanosomiasis. J Parasit Dis 2023; 47:167-184. [PMID: 36910316 PMCID: PMC9998817 DOI: 10.1007/s12639-022-01553-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 11/21/2022] [Indexed: 12/05/2022] Open
Abstract
During the late stage of Human African Trypanosomiasis (HAT), there is severe cytokine-driven inflammation, oxidative stress and organ damage. Controlling inflammation and oxidative damage presents unique therapeutic opportunities to improve treatment outcome. The current study sought to determine the putative impact of Coenzyme-Q10 (Co-Q10), a potent antioxidant and anti-inflammatory, on adverse inflammatory and oxidative events during Trypanosoma brucei rhodesiense (T.b.r) infection. Group one constituted the control; the second group was infected with T.b.r; the third group was orally administered with 200 mg/kg Co-Q10 for two weeks; thereafter, Co-Q10 administration continued after infection with T.b.r. Co-Q10 improved the survival rate of infected mice and prevented full blown parasite driven splenomegaly and hepatomegaly. Co-Q10 prevented characteristic T.b.r-driven breach of the blood brain barrier and improved neurological integrity among T.b.r infected mice. Co-Q10 protected from T.b.r-induced microcytic hypochromic anaemia and thrombocytopenia. T.b.r-induced oxidative stress in the vital organs was assuaged following exposure to Co-Q10. Co-Q10 blocked T.b.r-induced derangement of high density lipoprotein and triglyceride levels. Co-Q10 significantly abrogated T.b.r-driven elevation of serum TNF-α and IFN-γ levels. Moreover, T.b.r-induced kidney and liver damage was assuaged by Co-Q10 administration. Co-Q10 administration downregulated T.b.r-induced elevation of uric acid and C-reactive protein. Likewise, T.b.r infected mice receiving Co-Q10 exhibited normal brain architecture. In conclusion, treatment with Co-Q10 may be useful in protecting against T.b.r-mediated organ injury, lethal inflammation and oxidative stress commonly present in severe late stage HAT; and presents unique opportunities for an adjunct therapy for late stage HAT.
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Affiliation(s)
- Lynn Kitwan
- Department of Medical Microbiology Department, Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Kenya
| | - Celestine Makobe
- Department of Medical Microbiology Department, Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Kenya
| | - Raymond Mdachi
- Biotechnology Research Institute, Kenya Agricultural and Livestock Research Organization, Kikuyu, Kenya
| | | | - Alfred Orina Isaac
- Department of Pharmaceutical Sciences and Technology, Technical University of Kenya, Nairobi, Kenya
| | - James Nyabuga Nyariki
- Department of Biochemistry and Biotechnology, Technical University of Kenya, Nairobi, Kenya
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4
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Phan K, He Y, Bhatia S, Pickford R, McDonald G, Mazumder S, Timmins HC, Hodges JR, Piguet O, Dzamko N, Halliday GM, Kiernan MC, Kim WS. Multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis. Brain Commun 2022; 5:fcac340. [PMID: 36632187 PMCID: PMC9825811 DOI: 10.1093/braincomms/fcac340] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 11/02/2022] [Accepted: 12/12/2022] [Indexed: 12/27/2022] Open
Abstract
Amyotrophic lateral sclerosis is a rapidly progressing neurodegenerative disease characterized by the degeneration of motor neurons and loss of various muscular functions. Dyslipidaemia is prevalent in amyotrophic lateral sclerosis with aberrant changes mainly in cholesterol ester and triglyceride. Despite this, little is known about global lipid changes in amyotrophic lateral sclerosis or in relation to disease progression. The present study incorporated a longitudinal lipidomic analysis of amyotrophic lateral sclerosis serum with a comparison with healthy controls using advanced liquid chromatography-mass spectrometry. The results established that diglyceride, the precursor of triglyceride, was enriched the most, while ceramide was depleted the most in amyotrophic lateral sclerosis compared with controls, with the diglyceride species (18:1/18:1) correlating significantly to neurofilament light levels. The prenol lipid CoQ8 was also decreased in amyotrophic lateral sclerosis and correlated to neurofilament light levels. Most interestingly, the phospholipid phosphatidylethanolamine and its three derivatives decreased with disease progression, in contrast to changes with normal ageing. Unsaturated lipids that are prone to lipid peroxidation were elevated with disease progression with increases in the formation of toxic lipid products. Furthermore, in vitro studies revealed that phosphatidylethanolamine synthesis modulated TARDBP expression in SH-SY5Y neuronal cells. Finally, diglyceride, cholesterol ester and ceramide were identified as potential lipid biomarkers for amyotrophic lateral sclerosis diagnosis and monitoring disease progression. In summary, this study represents a longitudinal lipidomics analysis of amyotrophic lateral sclerosis serum and has provided new insights into multiple pathways of lipid dysregulation in amyotrophic lateral sclerosis.
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Affiliation(s)
| | | | | | - Russell Pickford
- Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, NSW, Australia
| | - Gordon McDonald
- The University of Sydney, Sydney Informatics Hub, Sydney, NSW, Australia
| | - Srestha Mazumder
- The University of Sydney, Brain and Mind Centre, Sydney, NSW, Australia
| | - Hannah C Timmins
- The University of Sydney, Brain and Mind Centre, Sydney, NSW, Australia
| | - John R Hodges
- The University of Sydney, Brain and Mind Centre, Sydney, NSW, Australia
| | - Olivier Piguet
- The University of Sydney, Brain and Mind Centre, Sydney, NSW, Australia,The University of Sydney, School of Psychology, Sydney, NSW, Australia
| | - Nicolas Dzamko
- The University of Sydney, Brain and Mind Centre, Sydney, NSW, Australia,The University of Sydney, School of Medical Sciences, Sydney, NSW, Australia
| | - Glenda M Halliday
- The University of Sydney, Brain and Mind Centre, Sydney, NSW, Australia,The University of Sydney, School of Medical Sciences, Sydney, NSW, Australia
| | - Matthew C Kiernan
- The University of Sydney, Brain and Mind Centre, Sydney, NSW, Australia,Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Woojin Scott Kim
- Correspondence to: W. S. Kim, Associate Professor Brain and Mind Centre, The University of Sydney Camperdown NSW 2050, Australia E-mail:
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González-Jamett A, Vásquez W, Cifuentes-Riveros G, Martínez-Pando R, Sáez JC, Cárdenas AM. Oxidative Stress, Inflammation and Connexin Hemichannels in Muscular Dystrophies. Biomedicines 2022; 10:biomedicines10020507. [PMID: 35203715 PMCID: PMC8962419 DOI: 10.3390/biomedicines10020507] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 02/13/2022] [Accepted: 02/15/2022] [Indexed: 12/16/2022] Open
Abstract
Muscular dystrophies (MDs) are a heterogeneous group of congenital neuromuscular disorders whose clinical signs include myalgia, skeletal muscle weakness, hypotonia, and atrophy that leads to progressive muscle disability and loss of ambulation. MDs can also affect cardiac and respiratory muscles, impairing life-expectancy. MDs in clude Duchenne muscular dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy and limb-girdle muscular dystrophy. These and other MDs are caused by mutations in genes that encode proteins responsible for the structure and function of skeletal muscles, such as components of the dystrophin-glycoprotein-complex that connect the sarcomeric-actin with the extracellular matrix, allowing contractile force transmission and providing stability during muscle contraction. Consequently, in dystrophic conditions in which such proteins are affected, muscle integrity is disrupted, leading to local inflammatory responses, oxidative stress, Ca2+-dyshomeostasis and muscle degeneration. In this scenario, dysregulation of connexin hemichannels seem to be an early disruptor of the homeostasis that further plays a relevant role in these processes. The interaction between all these elements constitutes a positive feedback loop that contributes to the worsening of the diseases. Thus, we discuss here the interplay between inflammation, oxidative stress and connexin hemichannels in the progression of MDs and their potential as therapeutic targets.
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Affiliation(s)
- Arlek González-Jamett
- Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile; (W.V.); (J.C.S.)
- Escuela de Química y Farmacia, Facultad de Farmacia, Universidad de Valparaíso, Valparaíso 2360102, Chile; (G.C.-R.); (R.M.-P.)
- Correspondence: (A.G.-J.); (A.M.C.)
| | - Walter Vásquez
- Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile; (W.V.); (J.C.S.)
| | - Gabriela Cifuentes-Riveros
- Escuela de Química y Farmacia, Facultad de Farmacia, Universidad de Valparaíso, Valparaíso 2360102, Chile; (G.C.-R.); (R.M.-P.)
| | - Rafaela Martínez-Pando
- Escuela de Química y Farmacia, Facultad de Farmacia, Universidad de Valparaíso, Valparaíso 2360102, Chile; (G.C.-R.); (R.M.-P.)
| | - Juan C. Sáez
- Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile; (W.V.); (J.C.S.)
| | - Ana M. Cárdenas
- Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile; (W.V.); (J.C.S.)
- Correspondence: (A.G.-J.); (A.M.C.)
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Lee IC, Chiang KL. Clinical Diagnosis and Treatment of Leigh Syndrome Based on SURF1: Genotype and Phenotype. Antioxidants (Basel) 2021; 10:antiox10121950. [PMID: 34943053 PMCID: PMC8750222 DOI: 10.3390/antiox10121950] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 11/30/2021] [Accepted: 12/03/2021] [Indexed: 11/17/2022] Open
Abstract
SURF1 encodes the assembly factor for maintaining the antioxidant of cytochrome c oxidase (COX) stability in the human electron respiratory chain. Mutations in SURF1 can cause Leigh syndrome (LS), a subacute neurodegenerative encephalopathy, characterized by early onset (infancy), grave prognosis, and predominant symptoms presenting in the basal ganglia, thalamus, brainstem, cerebellum, and peripheral nerves. To date, more than sixty different SURF1 mutations have been found to cause SURF1-associated LS; however, the relationship between genotype and phenotype is still unclear. Most SURF1-associated LS courses present as typical LS and cause early mortality (before the age of ten years). However, 10% of the cases present with atypical courses with milder symptoms and increased life expectancy. One reason for this inconsistency may be due to specific duplications or mutations close to the C-terminus of the SURF1 protein appearing to cause less protein decay. Furthermore, the treatment for SURF1-associated LS is unsatisfactory. A ketogenic diet is most often prescribed and has proven to be effective. Supplementing with coenzyme Q and other cofactors is also a common treatment option; however, the results are inconsistent. Importantly, anti-epileptic drugs such as valproate—which cause mitochondrial dysfunction—should be avoided in patients with SURF1-associated LS presenting with seizures.
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Affiliation(s)
- Inn-Chi Lee
- Division of Pediatric Neurology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
- Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Correspondence: ; Tel.: +886-4-2473-9535; Fax: +886-4-2471-0934
| | - Kuo-Liang Chiang
- Department of Pediatric Neurology, Kuang-Tien General Hospital, Taichung 43303, Taiwan;
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Fan HC, Lee HF, Yue CT, Chi CS. Clinical Characteristics of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes. Life (Basel) 2021; 11:life11111111. [PMID: 34832987 PMCID: PMC8617702 DOI: 10.3390/life11111111] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 10/11/2021] [Accepted: 10/16/2021] [Indexed: 12/12/2022] Open
Abstract
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, a maternally inherited mitochondrial disorder, is characterized by its genetic, biochemical and clinical complexity. The most common mutation associated with MELAS syndrome is the mtDNA A3243G mutation in the MT-TL1 gene encoding the mitochondrial tRNA-leu(UUR), which results in impaired mitochondrial translation and protein synthesis involving the mitochondrial electron transport chain complex subunits, leading to impaired mitochondrial energy production. Angiopathy, either alone or in combination with nitric oxide (NO) deficiency, further contributes to multi-organ involvement in MELAS syndrome. Management for MELAS syndrome is amostly symptomatic multidisciplinary approach. In this article, we review the clinical presentations, pathogenic mechanisms and options for management of MELAS syndrome.
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Affiliation(s)
- Hueng-Chuen Fan
- Department of Pediatrics, Tungs’ Taichung Metroharbor Hospital, Wuchi, Taichung 435, Taiwan; (H.-C.F.); (C.-T.Y.)
- Department of Medical Research, Tungs’ Taichung Metroharbor Hospital, Wuchi, Taichung 435, Taiwan
- Department of Rehabilitation, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 356, Taiwan
- Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan
| | - Hsiu-Fen Lee
- Department of Pediatrics, Taichung Veterans General Hospital, Taichung 407, Taiwan;
| | - Chen-Tang Yue
- Department of Pediatrics, Tungs’ Taichung Metroharbor Hospital, Wuchi, Taichung 435, Taiwan; (H.-C.F.); (C.-T.Y.)
| | - Ching-Shiang Chi
- Department of Pediatrics, Tungs’ Taichung Metroharbor Hospital, Wuchi, Taichung 435, Taiwan; (H.-C.F.); (C.-T.Y.)
- Correspondence: ; Tel.: +886-4-26581919-4301
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Youssef AM, Mohamed DA, Hussein S, Abdullah DM, Abdelrahman SA. Effects of Quercetin and Coenzyme Q10 on Biochemical, Molecular, and Morphological Parameters of Skeletal Muscle in Trained Diabetic Rats. Curr Mol Pharmacol 2021; 15:239-251. [PMID: 34061009 DOI: 10.2174/1874467214666210521170339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 01/28/2021] [Accepted: 01/29/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Diabetes mellitus (DM) affects the musculoskeletal system through its metabolic perturbations. Exercise modulates blood sugar levels and increases the body's sensitivity to insulin in patients with DM. OBJECTIVE This study aimed to investigate the potential effects of combined quercetin and coenzyme Q10 (CoQ10) supplements with or without exercise on the histological, biochemical and molecular structures of diabetic rat's skeletal muscle. METHOD A total of 64 adult male albino rats were divided into six groups: control, trained nondiabetic, non-trained diabetic, diabetic rats treated with combined CoQ10 and quercetin, diabetic rats with treadmill training, and diabetic rats treated with treadmill training and CoQ10 and quercetin. Blood and skeletal muscle samples were obtained from all groups for routine histological examination and biochemical determination of cytokine levels and protein activities. Quantitative real-time polymerase chain reaction (qRT-PCR) and morphometric analysis of PAS and Bax expressions were also performed. RESULTS Biochemical analysis revealed improvement in all studied parameters with combined CoQ10 and quercetin than exercise training alone. Combined treatment and exercise showed significant improvement in all parameters especially interleukin 6 and malondialdehyde. Fibronectin type III domain-containing protein 5 (FNDC5) expression and irisin levels increased in all trained groups but combined treatment with exercise significantly increased their levels than exercise alone. Histological analysis revealed improvement after exercise or combined treatment; however, when exercise was combined with CoQ10 and quercetin, marked improvement was observed. CONCLUSION the combination of CoQ10 and quercetin could be promising in preserving musculoskeletal function in patients with DM concomitantly with physical exercise.
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Affiliation(s)
- Amal M Youssef
- Department of Physiology, Faculty of Medicine, Taibah University, Medinah, Saudi Arabia
| | - Dalia A Mohamed
- Medical Histology and Cell Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Samia Hussein
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Doaa M Abdullah
- Pharmacology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Shaimaa A Abdelrahman
- Medical Histology and Cell Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
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9
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Pallardó FV, Pagano G, Rodríguez LR, Gonzalez-Cabo P, Lyakhovich A, Trifuoggi M. Friedreich Ataxia: current state-of-the-art, and future prospects for mitochondrial-focused therapies. Transl Res 2021; 229:135-141. [PMID: 32841735 DOI: 10.1016/j.trsl.2020.08.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 08/19/2020] [Accepted: 08/20/2020] [Indexed: 12/21/2022]
Abstract
Friedreich's Ataxia is an autosomal recessive genetic disease causing the defective gene product, frataxin. A body of literature has been focused on the attempts to counteract frataxin deficiency and the consequent iron imbalance, in order to mitigate the disease-associated pro-oxidant state and clinical course. The present mini review is aimed at evaluating the basic and clinical reports on the roles and the use of a set of iron chelators, antioxidants and some cofactors involved in the key mitochondrial functions. Extensive literature has focused on the protective roles of iron chelators, coenzyme Q10 and analogs, and vitamin E, altogether with varying outcomes in clinical studies. Other studies have suggested mitoprotective roles for other mitochondrial cofactors, involved in Krebs cycle, such as alpha-lipoic acid and carnitine, involved in acyl transport across the mitochondrial membrane. A body of evidence points to the strong antioxidant properties of these cofactors, and to their potential contribution in mitoprotective strategies in Friedreich's Ataxia clinical evolution. Thus, we suggest the rationale for planning combination strategies based on the 3 mitochondrial cofactors and of some antioxidants and iron binders as mitoprotective cocktails in Friedreich Ataxia patients, calling attention to clinical practitioners of the importance to implement clinical trials.
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Affiliation(s)
- Federico V Pallardó
- Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia-INCLIVA, Valencia, Spain; CIBER de Enfermedades Raras (CIBERER), Valencia, Spain.
| | - Giovanni Pagano
- Department of Chemical Sciences, Federico II Naples University, Naples, Italy
| | - Laura R Rodríguez
- Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia-INCLIVA, Valencia, Spain
| | - Pilar Gonzalez-Cabo
- Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia-INCLIVA, Valencia, Spain; CIBER de Enfermedades Raras (CIBERER), Valencia, Spain
| | - Alex Lyakhovich
- Vall d'Hebron Institut de Recerca, Barcelona, Catalunya, Spain; Institute of Molecular Biology and Biophysics of the "Federal Research Center of Fundamental and Translational Medicine", Novosibirsk, Russia
| | - Marco Trifuoggi
- Department of Chemical Sciences, Federico II Naples University, Naples, Italy
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Pastor-Maldonado CJ, Suárez-Rivero JM, Povea-Cabello S, Álvarez-Córdoba M, Villalón-García I, Munuera-Cabeza M, Suárez-Carrillo A, Talaverón-Rey M, Sánchez-Alcázar JA. Coenzyme Q 10: Novel Formulations and Medical Trends. Int J Mol Sci 2020; 21:E8432. [PMID: 33182646 PMCID: PMC7697799 DOI: 10.3390/ijms21228432] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 10/31/2020] [Accepted: 11/07/2020] [Indexed: 12/11/2022] Open
Abstract
The aim of this review is to shed light over the most recent advances in Coenzyme Q10 (CoQ10) applications as well as to provide detailed information about the functions of this versatile molecule, which have proven to be of great interest in the medical field. Traditionally, CoQ10 clinical use was based on its antioxidant properties; however, a wide range of highly interesting alternative functions have recently been discovered. In this line, CoQ10 has shown pain-alleviating properties in fibromyalgia patients, a membrane-stabilizing function, immune system enhancing ability, or a fundamental role for insulin sensitivity, apart from potentially beneficial properties for familial hypercholesterolemia patients. In brief, it shows a remarkable amount of functions in addition to those yet to be discovered. Despite its multiple therapeutic applications, CoQ10 is not commonly prescribed as a drug because of its low oral bioavailability, which compromises its efficacy. Hence, several formulations have been developed to face such inconvenience. These were initially designed as lipid nanoparticles for CoQ10 encapsulation and distribution through biological membranes and eventually evolved towards chemical modifications of the molecule to decrease its hydrophobicity. Some of the most promising formulations will also be discussed in this review.
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Affiliation(s)
| | | | | | | | | | | | | | | | - José A. Sánchez-Alcázar
- Centro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide), and Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III. Universidad Pablo de Olavide, 41013 Sevilla, Spain; (C.J.P.-M.); (J.M.S.-R.); (S.P.-C.); (M.Á.-C.); (I.V.-G.); (M.M.-C.); (A.S.-C.); (M.T.-R.)
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11
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Marioli C, Magliocca V, Petrini S, Niceforo A, Borghi R, Petrillo S, La Rosa P, Colasuonno F, Persichini T, Piemonte F, Massey K, Tartaglia M, Moreno S, Bertini E, Compagnucci C. Antioxidant Amelioration of Riboflavin Transporter Deficiency in Motoneurons Derived from Patient-Specific Induced Pluripotent Stem Cells. Int J Mol Sci 2020; 21:E7402. [PMID: 33036493 PMCID: PMC7582490 DOI: 10.3390/ijms21197402] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/01/2020] [Accepted: 10/01/2020] [Indexed: 12/20/2022] Open
Abstract
Mitochondrial dysfunction is a key element in the pathogenesis of neurodegenerative disorders, such as riboflavin transporter deficiency (RTD). This is a rare, childhood-onset disease characterized by motoneuron degeneration and caused by mutations in SLC52A2 and SLC52A3, encoding riboflavin (RF) transporters (RFVT2 and RFVT3, respectively), resulting in muscle weakness, ponto-bulbar paralysis and sensorineural deafness. Based on previous findings, which document the contribution of oxidative stress in RTD pathogenesis, we tested possible beneficial effects of several antioxidants (Vitamin C, Idebenone, Coenzyme Q10 and EPI-743, either alone or in combination with RF) on the morphology and function of neurons derived from induced pluripotent stem cells (iPSCs) from two RTD patients. To identify possible improvement of the neuronal morphotype, neurite length was measured by confocal microscopy after β-III tubulin immunofluorescent staining. Neuronal function was evaluated by determining superoxide anion generation by MitoSOX assay and intracellular calcium (Ca2+) levels, using the Fluo-4 probe. Among the antioxidants tested, EPI-743 restored the redox status, improved neurite length and ameliorated intracellular calcium influx into RTD motoneurons. In conclusion, we suggest that antioxidant supplementation may have a role in RTD treatment.
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Affiliation(s)
- Chiara Marioli
- Genetics and Rare Diseases Research Division, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy; (C.M.); (F.C.); (M.T.)
| | - Valentina Magliocca
- Department of Science, University Roma Tre, 00146 Rome, Italy; (V.M.); (T.P.)
- Unit of Neuromuscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine, Department of Neuroscience, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy; (A.N.); (R.B.); (S.P.); (F.P.); (E.B.)
| | - Stefania Petrini
- Confocal Microscopy Core Facility, Research Laboratories, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy;
| | - Alessia Niceforo
- Unit of Neuromuscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine, Department of Neuroscience, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy; (A.N.); (R.B.); (S.P.); (F.P.); (E.B.)
- Department of Science, LIME, University Roma Tre, 00146 Rome, Italy;
| | - Rossella Borghi
- Unit of Neuromuscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine, Department of Neuroscience, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy; (A.N.); (R.B.); (S.P.); (F.P.); (E.B.)
- Department of Science, LIME, University Roma Tre, 00146 Rome, Italy;
| | - Sara Petrillo
- Unit of Neuromuscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine, Department of Neuroscience, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy; (A.N.); (R.B.); (S.P.); (F.P.); (E.B.)
| | - Piergiorgio La Rosa
- Department of Psychology, Division of Neuroscience, Sapienza University of Rome, 00185 Rome, Italy;
| | - Fiorella Colasuonno
- Genetics and Rare Diseases Research Division, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy; (C.M.); (F.C.); (M.T.)
- Department of Science, LIME, University Roma Tre, 00146 Rome, Italy;
| | - Tiziana Persichini
- Department of Science, University Roma Tre, 00146 Rome, Italy; (V.M.); (T.P.)
| | - Fiorella Piemonte
- Unit of Neuromuscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine, Department of Neuroscience, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy; (A.N.); (R.B.); (S.P.); (F.P.); (E.B.)
| | - Keith Massey
- Science Director, Cure RTD Foundation, 6228 Northaven Rd., Dallas, TX 75230, USA;
| | - Marco Tartaglia
- Genetics and Rare Diseases Research Division, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy; (C.M.); (F.C.); (M.T.)
| | - Sandra Moreno
- Department of Science, LIME, University Roma Tre, 00146 Rome, Italy;
| | - Enrico Bertini
- Unit of Neuromuscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine, Department of Neuroscience, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy; (A.N.); (R.B.); (S.P.); (F.P.); (E.B.)
| | - Claudia Compagnucci
- Genetics and Rare Diseases Research Division, IRCCS Ospedale Pediatrico Bambino Gesù, 00146 Rome, Italy; (C.M.); (F.C.); (M.T.)
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12
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Arenas‐Jal M, Suñé‐Negre JM, García‐Montoya E. Coenzyme Q10 supplementation: Efficacy, safety, and formulation challenges. Compr Rev Food Sci Food Saf 2020; 19:574-594. [DOI: 10.1111/1541-4337.12539] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 11/26/2019] [Accepted: 01/03/2020] [Indexed: 12/13/2022]
Affiliation(s)
- Marta Arenas‐Jal
- Pharmacy and Pharmaceutical Technology Department, Faculty of Pharmacy and Food SciencesUniversity of Barcelona Barcelona Spain
| | - J. M. Suñé‐Negre
- Pharmacy and Pharmaceutical Technology Department, Faculty of Pharmacy and Food SciencesUniversity of Barcelona Barcelona Spain
| | - Encarna García‐Montoya
- Pharmacy and Pharmaceutical Technology Department, Faculty of Pharmacy and Food SciencesUniversity of Barcelona Barcelona Spain
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13
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The NRF2 Signaling Network Defines Clinical Biomarkers and Therapeutic Opportunity in Friedreich's Ataxia. Int J Mol Sci 2020; 21:ijms21030916. [PMID: 32019240 PMCID: PMC7037688 DOI: 10.3390/ijms21030916] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 01/27/2020] [Accepted: 01/29/2020] [Indexed: 02/06/2023] Open
Abstract
Friedreich’s ataxia (FA) is a trinucleotide repeats expansion neurodegenerative disorder, for which no cure or approved therapies are present. In most cases, GAA trinucleotide repetitions in the first intron of the FXN gene are the genetic trigger of FA, determining a strong reduction of frataxin, a mitochondrial protein involved in iron homeostasis. Frataxin depletion impairs iron–sulfur cluster biosynthesis and determines iron accumulation in the mitochondria. Mounting evidence suggests that these defects increase oxidative stress susceptibility and reactive oxygen species production in FA, where the pathologic picture is worsened by a defective regulation of the expression and signaling pathway modulation of the transcription factor NF-E2 p45-related factor 2 (NRF2), one of the fundamental mediators of the cellular antioxidant response. NRF2 protein downregulation and impairment of its nuclear translocation can compromise the adequate cellular response to the frataxin depletion-dependent redox imbalance. As NRF2 stability, expression, and activation can be modulated by diverse natural and synthetic compounds, efforts have been made in recent years to understand if regulating NRF2 signaling might ameliorate the pathologic defects in FA. Here we provide an analysis of the pharmaceutical interventions aimed at restoring the NRF2 signaling network in FA, elucidating specific biomarkers useful for monitoring therapeutic effectiveness, and developing new therapeutic tools.
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14
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Goschorska M, Gutowska I, Baranowska-Bosiacka I, Barczak K, Chlubek D. The Use of Antioxidants in the Treatment of Migraine. Antioxidants (Basel) 2020; 9:E116. [PMID: 32012936 PMCID: PMC7070237 DOI: 10.3390/antiox9020116] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 01/24/2020] [Accepted: 01/26/2020] [Indexed: 12/12/2022] Open
Abstract
Despite numerous studies concerning the pathophysiology of migraine, the exact molecular mechanism of disturbances underlying migraine is still unknown. Furthermore, oxidative stress is considered to play a significant role in migraine pathogenesis. The notion of oxidative stress in migraine patients has been discussed for several decades. Over the past few years, among the substances that could potentially be used for migraine treatment, particular attention has been paid to the so-called nutraceutics, including antioxidants. Antioxidants supplied with food prevent oxidative stress by inhibiting initiation, propagation, and the oxidative chain reaction itself. Additionally, the agents used so far in the prevention of migraine indeed show some anti-oxidative action. The antioxidants discussed in the present paper are increasingly more often used by migraine patients not only due to mild or even a lack of side effects but also because of their effectiveness (decreased frequency of migraine episodes or shortening of an episode duration). The present review provides a summary of the studies on nutraceuticals with antioxidative properties.
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Affiliation(s)
- Marta Goschorska
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powst. Wlkp. 72, 70-111 Szczecin, Poland; (I.B.-B.); (D.C.)
| | - Izabela Gutowska
- Department of Medical Chemistry, Pomeranian Medical University in Szczecin, Powst. Wlkp. 72, 70-111 Szczecin, Poland;
| | - Irena Baranowska-Bosiacka
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powst. Wlkp. 72, 70-111 Szczecin, Poland; (I.B.-B.); (D.C.)
| | - Katarzyna Barczak
- Department of Conservative Dentistry and Endodontics, Pomeranian Medical University in Szczecin, Powst. Wlkp. 72, 70-111 Szczecin, Poland;
| | - Dariusz Chlubek
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powst. Wlkp. 72, 70-111 Szczecin, Poland; (I.B.-B.); (D.C.)
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15
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Effects of oral administration of common antioxidant supplements on the energy metabolism of red blood cells. Attenuation of oxidative stress-induced changes in Rett syndrome erythrocytes by CoQ10. Mol Cell Biochem 2019; 463:101-113. [PMID: 31595423 DOI: 10.1007/s11010-019-03633-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 09/25/2019] [Indexed: 01/15/2023]
Abstract
Nutritional supplements are traditionally employed for overall health and for managing some health conditions, although controversies are found concerning the role of antioxidants-mediated benefits in vivo. Consistently with its critical role in systemic redox buffering, red blood cell (RBC) is recognized as a biologically relevant target to investigate the effects of oxidative stress. In RBC, reduction of the ATP levels and adenylate energy charge brings to disturbance in intracellular redox status. In the present work, several popular antioxidant supplements were orally administrated to healthy adults and examined for their ability to induce changes on the energy metabolism and oxidative status in RBC. Fifteen volunteers (3 per group) were treated for 30 days per os with epigallocatechin gallate (EGCG) (1 g green tea extract containing 50% EGCG), resveratrol (325 mg), coenzyme Q10 (CoQ10) (300 mg), vitamin C (1 g), and vitamin E (400 U.I.). Changes in the cellular levels of high-energy compounds (i.e., ATP and its catabolites, NAD and GTP), GSH, GSSG, and malondialdehyde (MDA) were simultaneously analyzed by ion-pairing HPLC. Response to oxidative stress was further investigated through the oxygen radical absorptive capacity (ORAC) assay. According to our experimental approach, (i) CoQ10 appeared to be the most effective antioxidant inducing a high increase in ATP/ADP, ATP/AMP, GSH/GSSG ratio and ORAC value and, in turn, a reduction of NAD concentration, (ii) EGCG modestly modulated the intracellular energy charge potential, while (iii) Vitamin E, vitamin C, and resveratrol exhibited very weak effects. Given that, the antioxidant potential of CoQ10 was additionally assessed in a pilot study which considered individuals suffering from Rett syndrome (RTT), a severe X-linked neuro-developmental disorder in which RBC oxidative damages provide biological markers for redox imbalance and chronic hypoxemia. RTT patients (n = 11), with the typical clinical form, were supplemented for 12 months with CoQ10 (300 mg, once daily). Level of lipid peroxidation (MDA production) and energy state of RBCs were analyzed at 2 and 12 months. Our data suggest that CoQ10 may significantly attenuate the oxidative stress-induced damage in RTT erythrocytes.
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16
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Macías FA, Mejías FJ, Molinillo JM. Recent advances in allelopathy for weed control: from knowledge to applications. PEST MANAGEMENT SCIENCE 2019; 75:2413-2436. [PMID: 30684299 DOI: 10.1002/ps.5355] [Citation(s) in RCA: 116] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Revised: 01/10/2019] [Accepted: 01/19/2019] [Indexed: 05/27/2023]
Abstract
Allelopathy is the biological phenomenon of chemical interactions between living organisms in the ecosystem, and must be taken into account in addressing pest and weed problems in future sustainable agriculture. Allelopathy is a multidisciplinary science, but in some cases, aspects of its chemistry are overlooked, despite the need for a deep knowledge of the chemical structural characteristics of allelochemicals to facilitate the design of new herbicides. This review is focused on the most important advances in allelopathy, paying particular attention to the design and development of phenolic compounds, terpenoids and alkaloids as herbicides. The isolation of allelochemicals is mainly addressed, but other aspects such as the analysis and activities of derivatives or analogs are also covered. Furthermore, the use of allelopathy in the fight against parasitic plants is included. The past 12 years have been a prolific period for publications on allelopathy. This critical review discusses future research areas in this field and the state of the art is analyzed from the chemist's perspective. © 2019 Society of Chemical Industry.
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Affiliation(s)
- Francisco A Macías
- Allelopathy Group, Department of Organic Chemistry, School of Sciences, Institute of Biomolecules (INBIO), University of Cadiz, Cádiz, Spain
| | - Francisco Jr Mejías
- Allelopathy Group, Department of Organic Chemistry, School of Sciences, Institute of Biomolecules (INBIO), University of Cadiz, Cádiz, Spain
| | - José Mg Molinillo
- Allelopathy Group, Department of Organic Chemistry, School of Sciences, Institute of Biomolecules (INBIO), University of Cadiz, Cádiz, Spain
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17
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Nagib MM, Tadros MG, Rahmo RM, Sabri NA, Khalifa AE, Masoud SI. Ameliorative Effects of α-Tocopherol and/or Coenzyme Q10 on Phenytoin-Induced Cognitive Impairment in Rats: Role of VEGF and BDNF-TrkB-CREB Pathway. Neurotox Res 2019; 35:451-462. [PMID: 30374909 DOI: 10.1007/s12640-018-9971-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 10/09/2018] [Accepted: 10/12/2018] [Indexed: 12/16/2022]
Abstract
Phenytoin is one of the most well-known antiepileptic drugs that cause cognitive impairment which is closely related to cAMP response element-binding protein (CREB) brain-derived neurotrophic factor (BDNF) signaling pathway. Moreover, vascular endothelial growth factor (VEGF), an endothelial growth factor, has a documented role in neurogenesis and neuronal survival and cognitive impairment. Therefore, this study aimed to investigate the influence of powerful antioxidants: α-Toc and CoQ10 alone or combined in the preservation of brain tissues and the maintenance of memory formation in phenytoin-induced cognitive impairment in rats. The following behavioral test novel object recognition and elevated plus maze were assessed after 14 days of treatment. Moreover, VEGF, BDNF, TrkB, and CREB gene expression levels in the hippocampus and prefrontal cortex were estimated using RT-PCR. Both α-Toc and CoQ10 alone or combined with phenytoin showed improvement in behavioral tests compared to phenytoin. Mechanistically, α-Toc and/or CoQ10 decreases the VEGF mRNA expression, while increases BDNF-TrKB-CREB mRNA levels in hippocampus and cortex of phenytoin-treated rats. Collectively, α-Toc and/or CoQ10 alleviated the phenytoin-induced cognitive impairment through suppressing oxidative damage. The underlying molecular mechanism of the treating compounds is related to the VEGF and enhancing BDNF-TrkB-CREB signaling pathway. Our study indicated the usefulness α-Toc or CoQ10 as an adjuvant to antiepileptic drugs with an advantage of preventing cognitive impairment and oxidative stress.
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Affiliation(s)
- Marwa M Nagib
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, KM 28 Cairo - Ismailia Road Ahmed Orabi District, Cairo, Egypt.
| | - Mariane G Tadros
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Rania M Rahmo
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, KM 28 Cairo - Ismailia Road Ahmed Orabi District, Cairo, Egypt
| | - Nagwa Ali Sabri
- Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Amani E Khalifa
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University seconded to 57357 Children Cancer Hospital, Cairo, Egypt
| | - Somaia I Masoud
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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18
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Sadeghiyan Galeshkalami N, Abdollahi M, Najafi R, Baeeri M, Jamshidzade A, Falak R, Davoodzadeh Gholami M, Hassanzadeh G, Mokhtari T, Hassani S, Rahimifard M, Hosseini A. Alpha-lipoic acid and coenzyme Q10 combination ameliorates experimental diabetic neuropathy by modulating oxidative stress and apoptosis. Life Sci 2019; 216:101-110. [DOI: 10.1016/j.lfs.2018.10.055] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 10/24/2018] [Accepted: 10/25/2018] [Indexed: 01/25/2023]
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19
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Abdelraouf ER, Kilany A, Hashish AF, Gebril OH, Helal SI, Hasan HM, Nashaat NH. Investigating the influence of ubiquinone blood level on the abilities of children with specific learning disorder. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2018; 54:39. [PMID: 30546250 PMCID: PMC6267631 DOI: 10.1186/s41983-018-0029-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 10/04/2018] [Indexed: 12/02/2022] Open
Abstract
Background Ubiquinone has antioxidant properties and has been linked to cognitive performance in some neuropsychiatric disorders. Its role in specific learning disorder manifestations has not been previously investigated. Therefore, the aim of this study was to measure the blood levels of ubiquinone in a group of children with specific learning disorder in comparison to typically developing children and to investigate the correlation between ubiquinone levels in children with specific learning disorder and some of their intellectual capabilities, reading, spelling and writing performance. Methods The study included 71 native Arabic speaking children: 31 in the specific learning disorder group and 40 in the typically developing (TD) group. The abilities of the children with specific learning disorder were evaluated by the Stanford-Binet Intelligence Scale-4th edition, the Dyslexia Assessment Test, and the Illinois Test of Psycholinguistic Abilities. The level of ubiquinone was measured in both groups by ELISA. Correlation between some aptitudes of children with specific learning disorder and the ubiquinone level was performed. Results The blood levels of ubiquinone in the children with specific learning disorder group were less than those in the TD group. Correlation analysis revealed a significant positive correlation between ubiquinone and the scores of backward digit span abilities. Conclusions Ubiquinone has a role in the auditory working memory performance of children with specific learning disorder (with impairment in reading). The decreased levels of ubiquinone in this sample of children with specific learning disorder could have participated in the pathogenesis of this disorder.
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Affiliation(s)
- Ehab Ragaa Abdelraouf
- 1Research on Children with Special Needs Department, Medical Research division, National Research Centre, Elbuhouth Street, 12622, Dokki, Cairo, Egypt.,2Learning Disability Research Clinic, Medical Research Centre of Excellence, National Research Centre, Cairo, Egypt
| | - Ayman Kilany
- 1Research on Children with Special Needs Department, Medical Research division, National Research Centre, Elbuhouth Street, 12622, Dokki, Cairo, Egypt.,3Pediatric Neurology Research Clinic, Medical Research Centre of Excellence, National Research Centre, Cairo, Egypt
| | - Adel F Hashish
- 1Research on Children with Special Needs Department, Medical Research division, National Research Centre, Elbuhouth Street, 12622, Dokki, Cairo, Egypt
| | - Ola Hosny Gebril
- 1Research on Children with Special Needs Department, Medical Research division, National Research Centre, Elbuhouth Street, 12622, Dokki, Cairo, Egypt
| | - Suzette Ibrahim Helal
- 1Research on Children with Special Needs Department, Medical Research division, National Research Centre, Elbuhouth Street, 12622, Dokki, Cairo, Egypt.,4Neurology Research Clinic, Medical Research Centre of Excellence, National Research Centre, Cairo, Egypt
| | - Haytham Mohamad Hasan
- 1Research on Children with Special Needs Department, Medical Research division, National Research Centre, Elbuhouth Street, 12622, Dokki, Cairo, Egypt.,5Neuropsychiatry Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Neveen Hassan Nashaat
- 1Research on Children with Special Needs Department, Medical Research division, National Research Centre, Elbuhouth Street, 12622, Dokki, Cairo, Egypt.,2Learning Disability Research Clinic, Medical Research Centre of Excellence, National Research Centre, Cairo, Egypt.,6Phoniatric Research Clinic, Medical Research Centre of Excellence, National Research Centre, Cairo, Egypt
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20
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Giorgio V, Schiavone M, Galber C, Carini M, Da Ros T, Petronilli V, Argenton F, Carelli V, Acosta Lopez MJ, Salviati L, Prato M, Bernardi P. The idebenone metabolite QS10 restores electron transfer in complex I and coenzyme Q defects. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS 2018; 1859:901-908. [PMID: 29694828 DOI: 10.1016/j.bbabio.2018.04.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 04/03/2018] [Accepted: 04/18/2018] [Indexed: 12/11/2022]
Abstract
Idebenone is a hydrophilic short-chain coenzyme (Co) Q analogue, which has been used as a potential bypass of defective complex I in both Leber Hereditary Optic Neuropathy and OPA1-dependent Dominant Optic Atrophy. Based on its potential antioxidant effects, it has also been tested in degenerative disorders such as Friedreich's ataxia, Huntington's and Alzheimer's diseases. Idebenone is rapidly modified but the biological effects of its metabolites have been characterized only partially. Here we have studied the effects of quinones generated during in vivo metabolism of idebenone with specific emphasis on 6-(9-carboxynonyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (QS10). QS10 partially restored respiration in cells deficient of complex I or of CoQ without inducing the mitochondrial permeability transition, a detrimental effect of idebenone that may offset its potential benefits [Giorgio et al. (2012) Biochim. Biophys. Acta 1817: 363-369]. Remarkably, respiration was largely rotenone-insensitive in complex I deficient cells and rotenone-sensitive in CoQ deficient cells. These findings indicate that, like idebenone, QS10 can provide a bypass to defective complex I; and that, unlike idebenone, QS10 can partially replace endogenous CoQ. In zebrafish (Danio rerio) treated with rotenone, QS10 was more effective than idebenone in allowing partial recovery of respiration (to 40% and 20% of the basal respiration of untreated embryos, respectively) and allowing zebrafish survival (80% surviving embryos at 60 h post-fertilization, a time point at which all rotenone-treated embryos otherwise died). We conclude that QS10 is potentially more active than idebenone in the treatment of diseases caused by complex I defects, and that it could also be used in CoQ deficiencies of genetic and acquired origin.
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Affiliation(s)
- Valentina Giorgio
- CNR Neuroscience Institute and Department of Biomedical Sciences, University of Padova, Padova, Italy
| | - Marco Schiavone
- CNR Neuroscience Institute and Department of Biomedical Sciences, University of Padova, Padova, Italy
| | - Chiara Galber
- CNR Neuroscience Institute and Department of Biomedical Sciences, University of Padova, Padova, Italy
| | - Marco Carini
- INSTM Trieste Unit, Department of Chemical and Pharmaceutical Sciences, University of Trieste, Trieste, Italy
| | - Tatiana Da Ros
- INSTM Trieste Unit, Department of Chemical and Pharmaceutical Sciences, University of Trieste, Trieste, Italy
| | - Valeria Petronilli
- CNR Neuroscience Institute and Department of Biomedical Sciences, University of Padova, Padova, Italy
| | | | - Valerio Carelli
- IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy; Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
| | - Manuel J Acosta Lopez
- Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, IRP Città della Speranza, Padova, Italy
| | - Leonardo Salviati
- Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, IRP Città della Speranza, Padova, Italy
| | - Maurizio Prato
- INSTM Trieste Unit, Department of Chemical and Pharmaceutical Sciences, University of Trieste, Trieste, Italy; Carbon Nanobiotechnology Laboratory CIC biomaGUNE, Donostia-San Sebastián, Spain; Basque Fdn Sci, Ikerbasque, Bilbao, Spain
| | - Paolo Bernardi
- CNR Neuroscience Institute and Department of Biomedical Sciences, University of Padova, Padova, Italy.
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Motawi TK, Darwish HA, Hamed MA, El-Rigal NS, Aboul Naser AF. Coenzyme Q10 and niacin mitigate streptozotocin- induced diabetic encephalopathy in a rat model. Metab Brain Dis 2017; 32:1519-1527. [PMID: 28560538 DOI: 10.1007/s11011-017-0037-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Accepted: 05/19/2017] [Indexed: 01/04/2023]
Abstract
Diabetic encephalopathy is an important complication of diabetes characterized by cognitive impairment, neurochemical and structural abnormalities. This study aimed to investigate the effect of coenzyme Q10 (CoQ10) and niacin as well as their combination in the treatment of encephalopathy associated with streptozotocin (STZ)- induced diabetes in rats. Glibenclamide (reference diabetic drug) and donepezil hydrochloride (acetylcholinesterase inhibitor) were also evaluated. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). One month after STZ injection, diabetic rats were treated with the aforementioned drugs for two weeks. The evaluation was done through measuring glucose level, total antioxidant capacity (TAC), interleukin 6 (IL6), DNA degradation as well as serotonin and noradrenaline as neurotransmitters. The present data illustrated that combining CoQ10 and niacin exhibiting the most potent effect in improving the measured parameters and ameliorating some of diabetes complications.
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Affiliation(s)
- Tarek K Motawi
- Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Hebatallah A Darwish
- Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
- Pharmacology, Toxicology and Biochemistry Department, Faculty of Pharmaceutical Science and Pharmaceutical Industries, Future University, Cairo, Egypt
| | - Manal A Hamed
- Therapeutic Chemistry Department, National Research Centre, 33El-Bohouth St, Giza, Dokki, 60014618, Egypt.
| | - Nagy S El-Rigal
- Therapeutic Chemistry Department, National Research Centre, 33El-Bohouth St, Giza, Dokki, 60014618, Egypt
| | - Asmaa F Aboul Naser
- Therapeutic Chemistry Department, National Research Centre, 33El-Bohouth St, Giza, Dokki, 60014618, Egypt
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Autophagy of mitochondria: a promising therapeutic target for neurodegenerative disease. Cell Biochem Biophys 2015; 70:707-19. [PMID: 24807843 DOI: 10.1007/s12013-014-0006-5] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The autophagic process is the only known mechanism for mitochondrial turnover and it has been speculated that dysfunction of autophagy may result in mitochondrial error and cellular stress. Emerging investigations have provided new understanding of how autophagy of mitochondria (also known as mitophagy) is associated with cellular oxidative stress and its impact on neurodegeneration. This impaired autophagic function may be considered as a possible mechanism in the pathogenesis of several neurodegenerative disorders including Parkinson's disease, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington disease. It can be suggested that autophagy dysfunction along with oxidative stress is considered main events in neurodegenerative disorders. New therapeutic approaches have now begun to target mitochondria as a potential drug target. This review discusses evidence supporting the notion that oxidative stress and autophagy are intimately associated with neurodegenerative disease pathogenesis. This review also explores new approaches that can prevent mitochondrial dysfunction, improve neurodegenerative etiology, and also offer possible cures to the aforementioned neurodegenerative diseases.
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Majumdar A, Nirwane A, Kamble R. New evidences of neurotoxicity of aroclor 1254 in mice brain: potential of coenzyme q10 in abating the detrimental outcomes. ENVIRONMENTAL HEALTH AND TOXICOLOGY 2014; 29:e2014001. [PMID: 24683537 PMCID: PMC3965848 DOI: 10.5620/eht.2014.29.e2014001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/17/2013] [Accepted: 12/03/2013] [Indexed: 06/03/2023]
Abstract
OBJECTIVES The present subacute study was designed to evaluate the effect of coenzyme Q 10 (CoQ10) in the 28 days aroclor 1254 exposure induced oxidative stress in mice brain. METHODS Biochemical estimations of brain lipid peroxidation (LPO), reduced glutathione (GSH), and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and acetyl cholinesterase (AChE), and histopathological investigations of brain tissue were carried out. RESULTS Oral exposure of aroclor 1254 (5 mg/kg) led to significant decrease in levels of GSH, and activities of SOD, CAT, GPx, and AChE, and increase in LPO. These aberrations were restored by CoQ10 (10 mg/kg, intraperitoneal injection [IP]). This protection offered was comparable to that of L-deprenyl (1 mg/kg, IP) which served as a reference standard. CONCLUSIONS Aroclor 1254 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in the brains of Swiss albino mice. Supplementation of CoQ10 abrogates these deleterious effects of aroclor 1254. CoQ10 also apparently enhanced acetyl cholinesterase activity which reflects its influence on the cholinergic system.
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Affiliation(s)
- Anuradha Majumdar
- Department of Pharmacology, Bombay College of Pharmacy, Kalina, Mumbai, India
| | - Abhijit Nirwane
- Department of Pharmacology, Bombay College of Pharmacy, Kalina, Mumbai, India
| | - Rahul Kamble
- Department of Pharmacology, Bombay College of Pharmacy, Kalina, Mumbai, India
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Barakat A, Shegokar R, Dittgen M, Müller RH. Coenzyme Q10 oral bioavailability: effect of formulation type. JOURNAL OF PHARMACEUTICAL INVESTIGATION 2013. [DOI: 10.1007/s40005-013-0101-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Sanoobar M, Eghtesadi S, Azimi A, Khalili M, Jazayeri S, Reza Gohari M. Coenzyme Q10 supplementation reduces oxidative stress and increases antioxidant enzyme activity in patients with relapsing–remitting multiple sclerosis. Int J Neurosci 2013; 123:776-82. [DOI: 10.3109/00207454.2013.801844] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
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Mancuso M, Orsucci D, Filosto M, Simoncini C, Siciliano G. Drugs and mitochondrial diseases: 40 queries and answers. Expert Opin Pharmacother 2012; 13:527-43. [DOI: 10.1517/14656566.2012.657177] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Tsoukala A, Bjørsvik HR. Synthetic Route Discovery and Introductory Optimization of a Novel Process to Idebenone. Org Process Res Dev 2011. [DOI: 10.1021/op200051v] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Anna Tsoukala
- Department of Chemistry, University of Bergen, Allégaten 41, N-5007 Bergen, Norway
| | - Hans-René Bjørsvik
- Department of Chemistry, University of Bergen, Allégaten 41, N-5007 Bergen, Norway
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