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Jan 21, 2025Keywords:
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Main Article Content
Role of peroxisome proliferator-activated receptor (PPARα) in mediating renoprotective effects of fumarate
Abstract
Fumarate has been reported to exert renoprotective actions. This study investigated a potential association between renoprotective activities of fumarate and peroxisome proliferator activated receptor (PPARα). PPARα wild type (WT) and knockout (KO) mice were randomly grouped into three groups; control (mineral oil + distilled water, 10 mL/kg/day, p.o.), fumarate (1 mg/kg/day, p.o.) and fenofibrate (100 mg/kg/day, p.o.). Mice were treated for 10 days, after which they were anaesthetized with xylazine + ketamine, 100 mg/kg i.p. Cortical blood flow (CBF) was then measured using a laser Doppler. Biochemical analyses were carried out. Fumarate reduced CBF in PPARα WT mice compared to PPAR KO mice (280.3 ± 34.2 vs 449.8 ± 15 PU, p<0.05). Nitric oxide production was significantly lower in fumarate-treated PPAR WT compared to PPAR KO mice (13.6 ± 1 vs 20.9 ± 3 μM/ng, p<0.05). Catalase activity
was insignificantly different in PPAR WT and KO mice treated with fumarate (p>0.05. Superoxide dismutase (SOD) activity was reduced by two-fold in PPAR WT mice compared to PPAR KO mice (p<0.05). This study demonstrates that the effect of fumarate on CBF, nitric oxide and L-arginine metabolism may be partially modulated through the PPARα downstream signalling pathway.
