title: Oxidative stress and hypoxia observed in the kidneys of mice after a 13-week oral administration of melamine and cyanuric acid combination.
abstract: Both melamine and cyanuric acid have low toxicity, but together they may cause serious lesions to the kidney, via an unknown mechanism. This study was aimed to estimate whether lesions to the kidney were relative to oxidative damage and hypoxia in the kidney after mice exposed to 1mg/kg/day, 5mg/kg/day or 25mg/kg/day of a mixture of melamine and cyanuric acid for 13 weeks. Pathological changes to the kidneys, oxidative stress and energy parameters and hypoxia-inducible factor-1α (HIF-1α) change in the kidneys were evaluated. Pathological changes were found in the distal tubules of kidneys, such as crystals, proteinaceous casts and compensatory expansion, indicating that the mixture induced toxicity to the kidney. The activities of total antioxidant capacity (TAC) and superoxide dismutase (SOD) and the concentration of glutathione (GSH) decreased, while the concentrations of lipid peroxidation (MDA) and protein carbonyl groups (PC) increased after exposure to the mixture, demonstrating that the mixture resulted in imbalance of antioxidant and reactive oxygen species (ROS) and excessive ROS induced oxidant damage to lipid and proteins in kidneys. The activities of malate dehydrogenase (MDH) and succinate dehyrogenase (SDH) decreased, however, the activity of lactic dehydrogenase (LDH) and the concentration of HIF-1α increased after exposure to the mixture. Accordingly, it was concluded that the mixture resulted in a hypoxic state in kidneys and that both oxidative stress and hypoxia contributed to the lesion of kidneys. The exact cause of oxidative damage and hypoxia is not clear, it might be caused by either a direct effect or by an indirect effect, which is secondary to substantial renal damage caused by tubular obstruction due to crystal formation.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Weigang 1, Nanjing 210095, China. Electronic address: lyj@njau.edu.cn.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Lv
authors.forename: Peichen
authors.initials: P
authors.lastname: Liu
authors.forename: Changlu
authors.initials: C
authors.lastname: Xiang
authors.forename: Hejun
authors.initials: H
authors.lastname: Yang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D000860:Hypoxia / Q000139:chemically induced*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007668:Kidney / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014227:Triazines; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005978:Glutathione; C004632:cyanuric acid; C011907:melamine
keywords: Hypoxia; Kidney; Mouse; Oxidative stress; The mixture of melamine and cyanuric acid