Resveratrol Mitigates Acetamiprid-Induced Cardiotoxicity in Rats via Modulation of Jak/Stat, p38 Mapk and mTOR Signaling Pathways

Acetamiprid (ACP) is a novel neonicotinoid insecticide used frequently to eradicate insect pests. Resveratrol (RSV) is a polyphenol used as a potential antioxidant, anti-inflammatory and antiapoptotic compound. The current research aimed to investigate the modulation of Jak/Stat, p38 Mapk, and mTOR signaling pathways by RSV in ACP-induced cardiotoxicity. Four equal groups of male rats (10 rats each) were treated daily for 90 days via oral intubation. Group 1 was the control; Group 2 received ACP (25 mg/kg b. wt); Group 3 received RSV (20 mg/kg b. wt); and Group 4 received both ACP and RSV. Gene expression and tissue proteins were analyzed in the heart while biochemical changes were estimated in serum. Histopathological and histochemical alterations of the cardiac tissues were also investigated. ACP administration showed elevations of mRNA expression of the inflammation-related genes (Jak, Stat, NF-κB, p38 Mapk) and tissue proteins (mTOR and TNF-α) in the myocardium. Significant serum high sensitivity C-reactive protein (hs-CRP) level and lactate dehydrogenase (LDH) activity were also recorded. Histopathology and immunohistochemistry showed myocardial infarction and inflammatory cell infiltration besides increased IL-6 protein expression. On the other hand, RSV treatment alleviated ACP-induced cardiotoxic actions and modulated the expression levels of the inflammation-related genes signaling pathways.