title: Melamine and cyanuric acid co-exposure causes renal dysfunction and structural damage via MAPKs and mitochondrial signaling.
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.
authors: College of Veterinary Medicine BK21 Plus Team, Chonnam National University, Gwangju 500-757, Republic of Korea; Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea.
authors: In-Chul
authors: IC
authors: Lee
authors: College of Veterinary Medicine BK21 Plus Team, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors: Je-Won
authors: JW
authors: Ko
authors: College of Veterinary Medicine BK21 Plus Team, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors: Sung-Hyeuk
authors: SH
authors: Park
authors: College of Veterinary Medicine BK21 Plus Team, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors: In-Sik
authors: IS
authors: Shin
authors: College of Veterinary Medicine BK21 Plus Team, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors: Changjong
authors: C
authors: Moon
authors: College of Veterinary Medicine BK21 Plus Team, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors: Sung-Ho
authors: SH
authors: Kim
authors: College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors: Yun-Bae
authors: YB
authors: Kim
authors: College of Veterinary Medicine BK21 Plus Team, Chonnam National University, Gwangju 500-757, Republic of Korea. Electronic address: toxkim@jnu.ac.kr.
authors: Jong-Choon
authors: JC
authors: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D005978:Glutathione / Q000378:metabolism; D015151:Immunoblotting; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014227:Triazines / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D004338:Drug Combinations; D014227:Triazines; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; C004632:cyanuric acid; C011907:melamine
keywords: Apoptosis; Cyanuric acid; Melamine; Mitogen-activated protein kinases; Nephrotoxicity