Lycopene suppresses α-cypermethrin nephrotoxicity: An insight into its modulatory effect on oxidative stress-mediated pro-inflammation, DNA damage and caspase apoptosis in Wistar rats

Abstract

Objective: Cypermethrin (CPM) is a synthetic pyrethroid pesticide with ubiquitous use in agriculture, but well associated with nephrotoxicity induction. However, CPM exposure is linked with human and animal systemic toxicity. Lycopene (LYP) is a lipid-soluble potent antioxidant abundant in tomatoes. The investigation thus explored whether LYP could mitigate CPM-induced nephrotoxicity via related mechanisms. Materials and Methods: The study design featured 4 groups: Control, LYP (10 mg/kg/day), CPM (25 mg/kg bw/day) and LYP (10 mg/kg bw/day) + CPM (25 mg/kg bw/day). The treatments of LYP and CPM were given for consecutive 28 days. Urea, uric acid and creatinine levels were estimated in serum, while glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) activities, and malondialdehyde (MDA), DNA damage, cytokines, interleukin-10 (IL-10), interleukin-6 (IL-6), interleukin-4 (IL-4), and tumor necrosis factor-α (TNF-α), caspase-9 and caspase-3 levels were estimated in the renal tissue sample. Histopathology and its amelioration were analyzed. Results: The sub-acute CPM exposure provoked renal damage with significantly elevated levels of creatinine, uric acid, and urea. Renal antioxidant homeostasis was markedly impaired via depressed GPx, CAT, and SOD renal activities, and increased MDA level. Marked DNA damage and profound increases in the renal levels of caspase-9, IL-6, TNF-α, and caspase-3 were found, whereas the renal IL-4 and IL-10 levels were evidently reduced in comparison to the control. Interestingly, the LYP co-administration abrogated the CPM-induced oxidative stress, proinflammation, apoptosis, and DNA fragmentation. Conclusion: Our findings indicate that LYP supplementation may protect the kidney from oxidative stress-related attacks of CPM.