Combined Chitosan and Ivy Leaf Extract Mitigate Deltamethrin‐Induced Hepatorenal and Reproductive Toxicity via <i> <scp>miR‐144</scp> </i> Antioxidant Signaling

Abstract

Deltamethrin (DM) is a common type II synthetic pyrethroid pesticide; however, increasing evidence indicates that long-term exposure can cause systemic toxicity. This toxicity is linked to inflammation due to oxidative stress and cell death, possibly involving microRNA disruption of antioxidant defenses. This study aimed to explore how a combination of chitosan and ivy leaf extract (Hedera helix) protects against liver, kidney, and reproductive toxicity caused by DM exposure. It specifically examines the role of miR-144 in antioxidant pathways. Forty-eight adult male Wistar rats were divided into eight groups. They received oral treatments for 90 days, including DM (0.6 mg/kg), chitosan (200 mg/kg), ivy leaf extract (50 mg/kg), or combinations of these. Liver and kidney functions, markers of oxidative stress (MDA, GPx, SOD), inflammatory markers (TNF-α, COX-2, MAPK14), apoptotic markers (Bax, Caspase-3, Birc5), and the expression of miR-144 were assessed, along with comprehensive histopathological and immunohistochemical evaluations. Subchronic DM exposure led to significant weight loss and multi-organ dysfunction. This was associated with a marked increase in lipid peroxidation and a decline in antioxidant defenses. Molecular analysis revealed that DM significantly increased miR-144 expression in the liver, kidney, and testis, with a strong negative correlation with SOD activity (r - 0.916 in the kidney and -0.911 in the liver). This redox imbalance was associated with an inflammatory response via MAPK14 and shifted the balance toward apoptosis. Notably, the combination of chitosan and ivy leaf extract provided greater protection than either treatment alone, with lowered miR-144 levels, restored antioxidant enzyme activity, and reduced pro-inflammatory and apoptotic signals, and a clear restoration of tissue structure toward normal. The findings suggest a superior combined protective effect. Chitosan acts by scavenging free radicals, while ivy leaf extract likely involves modulation of the miR-144-associated antioxidant pathway. This highlights the potential of using natural antioxidant combinations to counteract the long-term effects of pesticide toxicity.