Mitochondrial bioenergetics and redox dysfunction in nephrotoxicity induced by pyrethroid permethrin are ameliorated by flavonoid-rich fraction

The present study was designed to evaluate in vitro and in vivo the potential anti-inflammatory and nephroprotective potential of ethyl acetate fraction extracted from Fumaria officinalis (EAF) against permethrin (PER). Male wistar rats were treated daily by gavage during 7 days as follows: group C: negative control rats received 2 mL/kg bw of corn oil, group EAF: positive control rats received EAF at a dose of 200 mg/kg bw dissolved in water, group PER: rats received PER at a dose of 34.05 mg/kg bw and group (PER + EAF): rats received PER (34.05 mg/kg bw) and EAF (200 mg/kg bw). In vitro study showed the ability of EAF to inhibit protein denaturation and heat-induced hemolysis confirming its anti-inflammatory activity. In vivo, PER treatment decreased calcium (Ca) and phosphorus (P) levels and increased lactate dehydrogenase (LDH) activity in plasma. It induced oxidative stress objectified by an increase in the lipid peroxidation and protein oxidation and a perturbation of antioxidant system in kidney and mitochondria. The activities of NADH–ubiquinone reductase, ubiquinol–cytochrome C reductase and cytochrome C oxidase activities were reduced. These alterations were confirmed by histopathological studies. Co-treatment with EAF improved the antioxidant status and mitochondrial bioenergetics. The nephroprotective effects of EAF could be attributed to its modulation of detoxification enzymes and/or free radical scavenging actions.