Modulation of the Redox State and L-arginine Metabolism by Fumarate in Mitochondrial Fractions of the Rat Kidney
doi.org/10.26538/tjnpr/v6i8.27
Keywords:
Fumarate,, Mitochondrial metabolism,, Hydrogen peroxide,, ,Redox state,, Nitric oxideAbstract
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.
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