CDCT ‐induced nephrotoxicity in rat by apoptosis via metabolic disturbance

This study aims to investigate the CDCT-induced changes of morphology in kidney and metabolites and further explore the possible mechanisms of CDCT-induced nephrotoxicity.Sprague –Dawley rats were exposed to the CDCT at a clinical equivalent dose for 6  days. CDCT exposure can induce kidney injury and death. Pathological changes, including creatinine, urea nitrogen, and histopathology, were observed in rats. Furthermore, metabolomic-driven energy and glycerophospholipid metabolism pathway disorders, accompanied by remarkably changed key metabolit es, such as succinate, leukotriene B4 (LTB4), and cardiolipin (CL), are observed in the CDCT-induced nephrotoxicity. Functionally, succinate accumulation leads to mitochondrial damage, as evidence by the imbalance of complex I and complex II and an increase in mitochondrial reactive oxygen species (mito SOX). Meanwhile, LTB4 activated the NF- κB signaling, as shown by increased protein of p65, phosphor-p65, and decreased protein of IκBα and phosphor-IκBα. Eventually, the apoptosis pathway was triggered in response to reduced CL, inflammation, and mito SOX, as demonstrated by the expression of cyt c, Bax, Bcl-2, caspase-3, and caspas e-9. This study indicated that CDCT-induced metabolic disorders triggered nephrotoxicity and provided a comprehensive information to elucidate the mechanism of CDCT induced nephrotoxicity.
Source: Journal of Applied Toxicology - Category: Toxicology Authors: Tags: RESEARCH ARTICLE Source Type: research