From antioxidant defense system damage to programmed cell apoptosis: Understanding lethal mechanisms of cypermethrin on fish kidneys

Harmful effects of pesticide pollution on aquaculture have become increasingly urgent. The kidney, critical organ of the endocrine system in fish, is susceptible to some pollutants in the aquatic system. This study aimed to investigate the comprehensive effects and toxicological mechanisms of cypermethrin (CMN) on fish kidneys. The findings derived from the in vivo experiments demonstrated that exposure to CMN resulted in notable damage to the kidneys of grass carp, accompanied by impairment to the antioxidant defense system of kidney tissue, inducing severe oxidative stress. The activities of T-SOD, CAT, and GSH decreased, and lipid peroxidation product MDA content increased sharply. Subsequently, p-PERK, p-eIF2 alpha, GRP78, and IRE1 significantly increased, suggesting a disturbance in the endoplasmic reticulum (ER) homeostasis. In addition, excessive oxidative stress and ER stress initiated programmed apoptosis. At cellular level in vitro, the changes of CMN did on damage degree of grass carp kidney cells were verified. Toxicity mechanism was consistent with the in vivo test. The information provided herein emphasized the assessment of pollution caused by the toxic organic insecticide CMN effects on the food chain of marine organisms. The results of this study revealed potential nephrotoxic mechanisms of CMN in fish and provide essential data for the safety monitoring and rational application of CMN. Together, these results shed light on protein homeostasis mechanisms that may help manage misfolded proteins under oxidative stress conditions.