Melamine and cyanuric acid co-exposure causes renal dysfunction and structural damage via MAPKs and mitochondrial signaling

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...

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Veröffentlicht in:Food and chemical toxicology 2016-10, Vol.96, p.254-262
Hauptverfasser: Lee, In-Chul, Ko, Je-Won, Park, Sung-Hyeuk, Shin, In-Sik, Moon, Changjong, Kim, Sung-Ho, Kim, Yun-Bae, Kim, Jong-Choon
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Sprache:eng
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Zusammenfassung: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. •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.
ISSN:0278-6915
1873-6351
DOI:10.1016/j.fct.2016.08.013