Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Aug 26, 2015; 6(3): 240-248
Published online Aug 26, 2015. doi: 10.4331/wjbc.v6.i3.240
Effect of paricalcitol and enalapril on renal inflammation/oxidative stress in atherosclerosis
Kazim Husain, Edu Suarez, Angel Isidro, Wilfredo Hernandez, Leon Ferder
Kazim Husain, Edu Suarez, Angel Isidro, Leon Ferder, Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine and Health Sciences, Ponce, PR 00732, United States
Wilfredo Hernandez, Department of Biochemistry, Ponce School of Medicine and Health Sciences, Ponce, PR 00732, United States
Author contributions: Husain K performed the majority of the experiments, analyzed the data and wrote the paper; Suarez E performed the animal treatments, data recording and analysis; Isidro A performed physiological experiments; Hernandez W performed biochemical data and statistical analysis; Ferder L designed and coordinated the research.
Supported by A research grant from Abbott Pharmaceutical, United States.
Institutional review board statement: The animal protocol was designed to minimize pain and discomfort to the animals. The animals were acclimatized to laboratory conditions (25 °C, 12 h/12 h light/dark, 50% humidity, ad libitum access to food and water) for one week.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of Ponce School of Medicine (Protocol #LF-07).
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
Data sharing statement: This is a non-clinical study hence the technical appendix, statistical code, and data sets are not available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Kazim Husain, PhD, DABT, Professor, Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine and Health Sciences, PO Box 7004, Ponce, PR 00732, United States.
Telephone: +1-787-8402575 Fax: +1-787-8413736
Received: January 24, 2015
Peer-review started: January 28, 2015
First decision: March 6, 2015
Revised: May 26, 2015
Accepted: June 9, 2015
Article in press: June 11, 2015
Published online: August 26, 2015

AIM: To investigate the protective effect of paricalcitol and enalapril on renal inflammation and oxidative stress in ApoE-knock out mice.

METHODS: Animals treated for 4 mo as group (1) ApoE-knock out plus vehicle, group (2) ApoE-knock out plus paricalcitol (200 ng thrice a week), (3) ApoE-knock out plus enalapril (30 mg/L), (4) ApoE-knock out plus paricalcitol plus enalapril and (5) normal. Blood pressure (BP) was recorded using tail cuff method. The kidneys were isolated for biochemical assays using spectrophotometer and Western blot analyses.

RESULTS: ApoE-deficient mice developed high BP (127 ± 3 mmHg) and it was ameliorated by enalapril and enalapril plus paricalcitol treatments but not with paricalcitol alone. Renal malondialdehyde concentrations, p22phox, manganese-superoxide dismutase, inducible nitric oxide synthase (NOS), monocyte chemoattractant protein-1, tumor necrosis factor-alpha and transforming growth factor-β1 levels significantly elevated but reduced glutathione, CuZn-SOD and eNOS levels significantly depleted in ApoE-knock out animals compared to normal. Administration of paricalcitol, enalapril and combined together ameliorated the renal inflammation and oxidative stress in ApoE-knock out animals.

CONCLUSION: Paricalcitol and enalapril combo treatment ameliorates renal inflammation as well as oxidative stress in atherosclerotic animals.

Keywords: Atherosclerosis, Enalapril, Paricalcitol, Renal inflammation, Oxidative stress

Core tip: Although the protective efficacy of vitamin D and angiotensin converting enzyme inhibitors (ACEIs) have been studied in the cardiovascular system of atherosclerotic mice. However this is the first report to investigate the renal protection by paricalcitol and enalapril, alone or in combination in ApoE-deficient atherosclerotic mice. This innovative study clearly shows that vitamin D, ACEI and their combo ameliorated the renal inflammation and oxidative stress in ApoE-knock out animals by depleting the inflammatory and oxidative stress markers as well as restoring the renal antioxidant defense system in atherosclerotic mice. The combination of paricalcitol and enalapril warrants the clinical usefulness in renal atherosclerotic patients.