Cardioprotective Effects of Nano-Piperine Against Cypermethrin Toxicity Through Oxidative Stress, Histopathological and Immunohistochemical Studies in Male Wistar Rats

Abstract

Background: Cypermethrin (Cyp) is a synthetic derivative of pyrethroids, implicated in various organ toxicity. This study investigated the potential cardio-protective activity of nano-piperine (NP) against Cyp toxicity in adult Wister male rats. Methods: All animals in groups II, III, IV, and V were subjected to Cyp (50 mg/kg) for 15 days. After 1 h of receiving the Cyp dose, 3 doses of NP (125, 250, and 500 µg/kg/day) were administered to groups III, IV, and V, respectively, for 10 days. In Group VI, a dose of 500 µg/kg NP alone was given orally daily for 10 days. Result: The toxic effects were evaluated by an increase in serum cardiac injury biomarkers (lactate dehydrogenase, cardiac troponin I, creatine kinase-myoglobin binding, tissue lipid peroxidation, a decrease in antioxidative activity, such as glutathione, superoxide dismutase [SOD] and catalase, and upregulation of interleukins [interleukin 1β, interleukin 6]). Immunohistochemistry studies of proteins (nuclear factor-κB [NF-kB], apoptotic protease activating factor-1 [Apaf-1], 4-hydroxynonenal [4-HNE] and Bax) showed enhanced expression, and histopathological examination revealed myolysis, loss of striation and hemorrhages indicating heart toxicity in the animals. Administration of NP significantly ameliorated all the changes caused by Cyp, such as a decrease in the levels of serum cardiac injury markers, an increase of antioxidative parameters, decrease in expression of inflammatory cytokines and NF-kB, Apaf-1, 4-HNE, and Bax, as shown by immunohistochemistry studies. Furthermore, all the histopathological changes were reduced to near the values of the control. Conclusion: Collectively our findings indicated that NP could be a potent nutraceutical exhibiting cardioprotective effects against Cyp-induced cardiotoxicity in rats.