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Huang Q, Wang Y, Zhang Z, Wu M, Liu J, Chen J, Li J, Yao Y, Guo C, Zhao D, Qi W, Li X. Organ dysfunction induced by hemorrhagic shock: From mechanisms to therapeutic medicines. Pharmacol Res 2025; 216:107755. [PMID: 40315969 DOI: 10.1016/j.phrs.2025.107755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 04/03/2025] [Accepted: 04/27/2025] [Indexed: 05/04/2025]
Abstract
Hemorrhagic shock (HS) leads to organ dysfunction, which increases the incidence of unfavorable outcomes in patients. However, adjuvant drug therapy for HS has not been widely accepted, and the benefits of vasopressors are generally considered to have insufficient evidence. Energy homeostasis disruption and excessive immune system activation are the main mechanisms underlying HS-induced organ dysfunction. Recent reports on HS animal models and clinical trials have revealed potential drugs that target the immune response, oxidative damage, and energy homeostasis in HS, providing new insights for the treatment of HS-induced organ dysfunction. In this review, we first discuss the pathophysiology of organ dysfunction involved in HS injury and then systematically review potential drugs that regulate immunity, the inflammatory response, oxidative damage, energy homeostasis, and cell death. We also review the available drugs with clinical evidence of HS-induced organ dysfunction efficacy. Treatment strategies combined with an improved understanding of the organ injury mechanisms of HS may help identify and develop targeted therapeutic modalities that mitigate severe organ dysfunction and reduce mortality caused by HS injury.
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Affiliation(s)
- Qingxia Huang
- Research Center of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130021, China; Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China
| | - Yisa Wang
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China
| | - Zepeng Zhang
- Research Center of Traditional Chinese Medicine, College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130021, China; Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China
| | - Mingxia Wu
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China
| | - Jiaqi Liu
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China
| | - Jinjin Chen
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China
| | - Jing Li
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China
| | - Yao Yao
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China
| | - Chen Guo
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China
| | - Daqing Zhao
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China
| | - Wenxiu Qi
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China.
| | - Xiangyan Li
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China.
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Zhang FH, Liu Y, Dong XB, Hao H, Fan KL, Meng XQ, Kong L. Shenmai Injection Upregulates Heme Oxygenase-1 to Confer Protection Against Severe Acute Pancreatitis. J Surg Res 2020; 256:295-302. [PMID: 32712444 DOI: 10.1016/j.jss.2020.06.035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 06/01/2020] [Accepted: 06/16/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND To explore the mechanism of Shenmai injection (SMI) on severe acute pancreatitis (SAP) through heme oxygenase-1 (HO-1) signaling. METHODS A total of 40 male Sprague-Dawley (SD) rats (220-260 g) were grouped into the following four categories (n = 10): SAP + SMI + Zinc protoporphyrin (ZnPP), SAP + SMI, SAP, and sham surgery groups. ZnPP is a specific inhibitor of HO-1. Four percent of sodium taurocholate (1 mL/kg) was retrogradely injected via the pancreatic duct to induce the SAP model. The SAP group rats received 1.6 mL/kg saline by intravenous injection 30 min after the induction of SAP. The SAP + SMI group rats received 1.6 mL/kg SMI by intravenous injection 30 min after the induction of SAP. The SAP + SMI + ZnPP group rats received an intravenous injection of 1.6 mL/kg SMI and intraperitoneal administration of 30 mg/kg ZnPP 30 min after the SAP induction. Twenty-four hours after the SAP induction, blood samples were collected for the measurement of amylase, lipase, creatinine, myeloperoxidase, interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and HO-1 level, while tissue specimens were harvested for the determination of HO-1, TNF-α, and IL-10 mRNA level. Meanwhile, histopathological changes in organs (pancreas, lung, and kidney) were stored. RESULTS The serum concentration of amylase, lipase, creatinine, and myeloperoxidase was higher in the SAP group than in the SAP + SMI group. Treatment with SMI increased HO-1 and IL-10 level and reduced TNF-α level in serum and tissues compared to the SAP group (P < 0.05). Treatment with SMI abolished the organ-damaging effects of SAP (P < 0.05). Furthermore, suppression of HO-1 expression by ZnPP canceled the aforementioned effects. CONCLUSIONS SMI confers protection against the SAP-induced systemic inflammatory response and multiple organs damage via HO-1 upregulation.
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Affiliation(s)
- Fei-Hu Zhang
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China; Department of Emergency Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
| | - Yang Liu
- Department of Emergency Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xiao-Bin Dong
- Department of Emergency Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Hao Hao
- Department of Emergency Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Kai-Liang Fan
- Department of Emergency Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xian-Qing Meng
- Department of Emergency Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Li Kong
- Department of Emergency Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
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Mao E. Intensive management of severe acute pancreatitis. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:687. [PMID: 31930088 PMCID: PMC6944592 DOI: 10.21037/atm.2019.10.58] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Accepted: 10/10/2019] [Indexed: 12/12/2022]
Abstract
To investigate an optimal management bundle to improve the survival rate of severe acute pancreatitis (SAP). We constructed a treatment bundle based on our clinical investigation, literature, and empirical practice. Intensive management during the acute response stage and infection stage comprised eight main issues: etiology, diagnosis, fluid resuscitation, support of organ function, abdominal compartment syndrome (ACS), enteral nutrition, intestinal function, and antibiotics. The intensive management plan included a time-dependent plan for the eight main issues and goal-directed therapy. The plan must be started within the prescribed time (time-dependent endeavors) and must involve the right strategies, right sequence, and right ward for each individual. Effective goal-directed therapy and essential treatment measures must be performed within a specified period of time, and treatment efficacy should be regularly assessed. In 2010, intensive management was initiated in China. Intensive management has significant effects on SAP. This strategy was adopted by 36 hospitals in China, resulting in significant improvements in prognoses. Some criteria of intensive management were adopted by the International Association of Pancreatology (IAP)/American Pancreatic Association Working Group Acute Pancreatitis Guidelines in 2013. Intensive management is an important efficacy-based treatment strategy that can significantly ameliorate prognoses.
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Affiliation(s)
- Enqiang Mao
- Department of Emergency, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Nabzdyk CS, Bittner EA. Vitamin C in the critically ill - indications and controversies. World J Crit Care Med 2018; 7:52-61. [PMID: 30370227 PMCID: PMC6201324 DOI: 10.5492/wjccm.v7.i5.52] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2018] [Revised: 08/04/2018] [Accepted: 08/21/2018] [Indexed: 02/06/2023] Open
Abstract
Ascorbic acid (vitamin C) elicits pleiotropic effects in the body. Among its functions, it serves as a potent anti-oxidant, a co-factor in collagen and catecholamine synthesis, and a modulator of immune cell biology. Furthermore, an increasing body of evidence suggests that high-dose vitamin C administration improves hemodynamics, end-organ function, and may improve survival in critically ill patients. This article reviews studies that evaluate vitamin C in pre-clinical models and clinical trials with respect to its therapeutic potential.
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Affiliation(s)
- Christoph S Nabzdyk
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
| | - Edward A Bittner
- Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
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Ding SS, Sun P, Zhang Z, Liu X, Tian H, Huo YW, Wang LR, Han Y, Xing JP. Moderate Dose of Trolox Preventing the Deleterious Effects of Wi-Fi Radiation on Spermatozoa In vitro through Reduction of Oxidative Stress Damage. Chin Med J (Engl) 2018; 131:402-412. [PMID: 29451144 PMCID: PMC5830824 DOI: 10.4103/0366-6999.225045] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Background: The worsening of semen quality, due to the application of Wi-Fi, can be ameliorated by Vitamin E. This study aimed to demonstrate whether a moderate dose of trolox, a new Vitamin E, inhibits oxidative damage on sperms in vitro after exposure to Wi-Fi radiation. Methods: Each of the twenty qualified semen, gathered from June to October 2014 in eugenics clinic, was separated into four aliquots, including sham, Wi-Fi-exposed, Wi-Fi plus 5 mmol/L trolox, and Wi-Fi plus 10 mmol/L trolox groups. At 0 min, all baseline parameters of the 20 samples were measured in sequence. Reactive oxygen species, glutathione, and superoxide dismutase were evaluated in the four aliquots at 45 and 90 min, as were sperm DNA fragments, sperm mitochondrial potential, relative amplification of sperm mitochondrial DNA, sperm vitality, and progressive and immotility sperm. The parameters were analyzed by one-way analysis of variance and Tukey's posttest. Results: Among Wi-Fi plus 5 mmol/L trolox, Wi-Fi-exposed and Wi-Fi plus 10 mmol/L trolox groups, reactive oxygen species levels (45 min: 3.80 ± 0.41 RLU·10−6·ml−1 vs. 7.50 ± 0.35 RLU·10−6·ml−1 vs. 6.70 ± 0.47 RLU·10−6·ml−1, P < 0.001; 90 min: 5.40 ± 0.21 RLU·10−6·ml−1 vs. 10.10 ± 0.31 RLU·10−6·ml−1 vs. 7.00 ± 0.42 RLU·10−6·ml−1, P < 0.001, respectively), percentages of tail DNA (45 min: 16.8 ± 2.0% vs. 31.9 ± 2.5% vs. 61.3 ± 1.6%, P < 0.001; 90 min: 19.7 ± 1.5% vs. 73.7 ± 1.3% vs. 73.1 ± 1.1%, P < 0.001, respectively), 8-hydroxy-2’-deoxyguanosine (45 min: 51.89 ± 1.46 pg/ml vs. 104.89 ± 2.19 pg/ml vs. 106.11 ± 1.81 pg/ml, P = 0.012; 90 min: 79.96 ± 1.73 pg/ml vs. 141.73 ± 2.90 pg/ml vs. 139.06 ± 2.79 pg/ml; P < 0.001), and percentages of immotility sperm (45 min: 27.7 ± 2.7% vs. 41.7 ± 2.2% vs. 41.7 ± 2.5%; 90 min: 29.9 ± 3.3% vs. 58.9 ± 4.0% vs. 63.1 ± 4.0%; all P < 0.001) were lowest, and glutathione peroxidase (45 min: 60.50 ± 1.54 U/ml vs. 37.09 ± 1.77 U/ml vs. 28.18 ± 1.06 U/ml; 90 min: 44.61 ± 1.23 U/ml vs. 16.86 ± 0.93 U/ml vs. 29.94 ± 1.56 U/ml; all P < 0.001), percentages of head DNA (45 min: 83.2 ± 2.0% vs. 68.2 ± 2.5% vs. 38.8 ± 1.6%; 90 min: 80.3 ± 1.5% vs. 26.3 ± 1.3% vs. 26.9 ± 1.1%; all P < 0.001), percentages of sperm vitality (45 min: 89.5 ± 1.6% vs. 70.7 ± 3.1% vs. 57.7 ± 2.4%; 90 min: 80.8 ± 2.2% vs. 40.4 ± 4.0% vs. 34.7 ± 3.9%; all P < 0.001), and progressive sperm (45 min: 69.3 ± 2.7% vs. 55.8 ± 2.2% vs. 55.4 ± 2.5%; 90 min: 67.2 ± 3.3% vs. 38.2 ± 4.0% vs. 33.9 ± 4.0%; all P < 0.001) were highest in Wi-Fi plus 5 mmol/L trolox group at 45 and 90 min, respectively. Other parameters were not affected, while the sham group maintained the baseline. Conclusion: This study found that 5 mmol/L trolox protected the Wi-Fi-exposed semen in vitro from the damage of electromagnetic radiation-induced oxidative stress.
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Affiliation(s)
- Shang-Shu Ding
- Department of Urology, School of Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Ping Sun
- Department of Urology, School of Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Zhou Zhang
- Department of Andrology, Shaanxi Maternal and Child Care Service Center, Xi'an, Shaanxi 710061, China
| | - Xiang Liu
- Department of Andrology, Shaanxi Maternal and Child Care Service Center, Xi'an, Shaanxi 710061, China
| | - Hong Tian
- Research Center of Reproduction Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Yong-Wei Huo
- Research Center of Reproduction Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Li-Rong Wang
- Research Center of Reproduction Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Yan Han
- Department of Biochemistry, Institute of Biochemistry and Molecular Medicine, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
| | - Jun-Ping Xing
- Department of Urology, School of Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
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The additive effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 function in diabetic rats. Sci Rep 2017; 7:13532. [PMID: 29051569 PMCID: PMC5648883 DOI: 10.1038/s41598-017-13206-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Accepted: 05/30/2017] [Indexed: 01/26/2023] Open
Abstract
Hyperglycemia-induced oxidative stress is usually found in diabetic condition. 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, statins, are widely used as cholesterol-lowering medication with several "pleiotropic" effects in diabetic patients. This study aims to evaluate whether the protective effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 (Oat3) function involve the modulation of oxidative stress and pancreatic function in type 1 diabetic rats. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg BW). Atorvastatin and insulin as single or combined treatment were given for 4 weeks after diabetic condition had been confirmed. Diabetic rats demonstrated renal function and renal Oat3 function impairment with an increased MDA level and decreased SOD protein expression concomitant with stimulation of renal Nrf2 and HO-1 protein expression. Insulin plus atorvastatin (combined) treatment effectively restored renal function as well as renal Oat3 function which correlated with the decrease in hyperglycemia and oxidative stress. Moreover, pancreatic inflammation and apoptosis in diabetic rats were ameliorated by the combined drugs treatment. Therefore, atorvastatin plus insulin seems to exert the additive effect in improving renal functionby alleviating hyperglycemiaand the modulation of oxidative stress, inflammation and apoptosis.
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