Melamine and cyanuric acid co-exposure causes renal dysfunction and structural damage via MAPKs and mitochondrial signaling. (October 2016)

• Record Type: Journal Article
• Authors: Lee, In-Chul; Ko, Je-Won; Park, Sung-Hyeuk; Shin, In-Sik; Moon, Changjong; Kim, Sung-Ho; Kim, Yun-Bae; Kim, Jong-Choon
• Is Part Of: Food and chemical toxicology. Volume 96(2016)
• Page Start: 254
• Page End: 262
• Publication Date: 2016-10
• Subjects: Melamine -- Cyanuric acid -- Nephrotoxicity -- Mitogen-activated protein kinases -- Apoptosis; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2016.08.013
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Both melamine and cyanuric acid have low toxicity, but combined exposure to melamine and cyanuric acid (M + CA) was reported to cause unexpected toxicological synergy on kidney damage. In this study, we investigated the role of oxidative stress and apoptotic changes in the nephrotoxicity caused by M + CA in rats. M + CA treatment caused an increase in the kidney weight, serum blood urea nitrogen or creatinine levels in a dose-dependent manner. With severe morphological and histological changes in kidneys, M + CA markedly elevated lipid peroxidation and suppressed antioxidant enzyme activities. M + CA treatment induced apoptotic changes in renal tubular cells. Additionally, exposure to M + CA increased phosphorylation of mitogen-activated protein kinases (MAPKs) coincided with increased Bax level and decreased Bcl2 level, resulting in caspase-3 activation. In summary, oxidative stress and simultaneous MAPKs and mitochondrial/caspase activation may be related to renal tubular cell apoptosis caused by M + CA. Highlights: M + CA caused functional and histopathological alteration in the kidneys. M + CA increased lipid peroxidation and decreased antioxidant enzyme activities in the kidneys. M + CA induced renal tubular cell apoptotic changes in the kidneys. M + CA caused phosphorylation of mitogen-activated protein kinases (MAPKs). M + CA increased Bax and decreased Bcl2 levels with caspase-3 activation in the kidneys.