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

Abstract

Recent studies suggest that mitochondrial bioenergetics and oxidative status perturbations may be common mechanisms involved in the progression of renal damage. The present study aimed to evaluate in vitro the potential anti-inflammatory using membrane stabilization and protein denaturation inhibition assays and in vivo protective effect of flavonoid- rich fraction from Fumaria officinalis (EAF) against permethrin (PER) induced nephrotoxicity in male rat. Animals were allocated into four groups: control; EAF (200 mg/Kg BW); PER (34.05 mg/Kg BW); and PER (34.05 mg/Kg BW) + EAF (200 mg/Kg BW) for 7 days. Our results suggest that EAF inhibited significantly protein denaturation and restored membrane stabilization. In vivo , permethrin-treated rats caused a substantial reduction of body weight gain and plasma calcium (Ca), phosphorus (P) and vitamin C levels as well as an increase of absolute and relative kidney weights and plasma lactate dehydrogenase (LDH) activity and kidney and mitochondria thiobarbituric acid reactive substance (TBARS), advanced oxidation protein product (AOPP) and protein carbonyl (PCO) levels. PER also caused renal and mitochondrial enzymatic and non-enzymatic antioxidant perturbation as well as mitochondrial NADH-ubiquinone reductase (complex I), ubiquinol cytochrome c reductase (complex III) and cytochrome c oxidase (complex IV) activities reduction associated with renal histopathological alterations. However, co-administration of EAF to the PER group restored oxidative status and mitochondrial bioenergetics. We suggest that EAF may be considered as a future therapeutic anti-inflammatory and may be used singly or as a co-therapeutic in the treatment of diseases associated with mitochondrial oxidative stress.