Modulation of the Redox State and L-arginine Metabolism by Fumarate in Mitochondrial Fractions of the Rat Kidney

Osaze Edosuyi1,2*, Myung Choi2, Ighodaro Igbe1, Adebayo Oyekan2
1Department of Pharmacology & Toxicology, Faculty of Pharmacy, University of Benin PMB 1154, Benin City, Nigeria
2Center for cardiovascular diseases, Gray Hall Suites, Rm 256, College of Pharmacy & Health Sciences, Texas Southern University, 3100, Cleburne Street, Houston, Texas, USA

Corresponding Author: [email protected]; Tel: +2348025228545
Recieved Date: 06 July 2022; Accepted Date: 21 August 2022; Published Date: 03 September
Citation: Edosuyi O, Choi M, Igbe I, Oyekan A.  Modulation of the Redox State and L-arginine Metabolism by Fumarate in Mitochondrial Fractions of the Rat Kidney. Trop J Nat Prod Res. 2022; 6(8):1326-1330.
© 2022 Edosuyi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Fumarate, a natural product, has been reported to modify the redox state and enhance nitric oxide (NO) synthesis in hypertensive rats. Considering the vital link between redox chemistry, L-arginine metabolism, and renal physiology, this study investigated fumarate for any effect on these parameters in normotensive rats. Kidneys were excised from anaesthetized (ketamine + xylazine) (100 mg/kg, i.p) Sprague Dawley rats. The renal cortex/medulla was homogenized to isolate the respective mitochondria fractions. The fractions were stimulated with angiotensin II (AII) (3, 10, 30 and 100 nM) to induce hydrogen peroxide (H2O2) production and incubated with fumarate (0.3,1, 3 and 10 µM) for 1 hour. Biochemical analyses were performed on these fractions. Fumarate (3 & 10 µM) exerted significant reductions in AII-induced H2O2 production in the cortex (p < 0.05). Fumarate reduced H2O2 in the medulla at 3 µM and exerted a time-related effect at 10 µM, compared to baseline (p < 0.05). Similarly, 3µM of fumarate significantly increased SOD activity in the medulla (p < 0.05). Catalase activity in the cortex peaked above baseline at 3 µM of fumarate only (2363.5 ± 332.2 vs 802.8 ± 189.1 units/ng, p < 0.01). However, fumarate increased catalase activity at all concentrations in the medulla (p < 0.05). Fumarate evoked a peak increase in NO and arginase activity at 3 µM in the cortex (p < 0.05). The data shows that fumarate improved the redox state via upregulation of SOD and CAT activities and may exert renoprotective action via an increase in NO.

Keywords: Fumarate, Mitochondrial metabolism, Hydrogen peroxide, Redox state, Nitric oxide
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ISSN: 2616-0684 (Print)
ISSN: 2616-0692 (Online)
DOI: 10.26538/tjnpr
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