Toxicopathological and Molecular Studies on Imidacloprid and Hexaflumuron-induced Hepatorenal Toxicity in Rats.

Abstract Pesticides are considered the main source of environmental pollution and causing severe hazardous effects on humans and livestock. Imidacloprid (IC) and hexaflumuron (HFM) are broadly used insecticides for crop protection in the world. Some studies discussed IC toxicity in rats, but the toxicity of HFM doesn’t elucidate yet. So that, the current study aimed to investigate the pathogenesis and the mechanistic way of both IC and HFM induced hepatorenal toxicity in rats with comprehensive insight into its molecular mechanism. 21 male Wistar albino rats were divided into 3 groups as the following: group (1), normal saline; group (2), receiving IC; and group (3), receiving HFM. All the following materials were orally administered every day for 28 days. At the end, all rats were euthanized to collect blood and organ samples (liver and kidneys). The results revealed behavioral alterations in walking, body tension, alertness, and head movement as well as a decrease in body weight of rats receiving either IC or HFM. In addition to increasing the levels of MDA with decreasing GHS levels in liver and kidney homogenates. Both liver and kidney tissues showed extensive histopathological alterations associated with increasing the serum levels of ALT, AST, urea, and creatinine as well as reduction in total proteins, albumin, and globulin levels. Furthermore, there was upregulation of m-RNA levels of caspase-3, JNK, and HO-1 genes with strong positive reaction of caspase-3, TNF-ὰ and NF-KB proteins in both liver and kidneys of rats receiving either IC or HFM compared with the control group. We can conclude that both IC and HFM induced oxidative hepatorenal damage via ROS overproduction that activate NF-KB signaling pathways and mitochondrial and JNK dependent apoptosis pathway.