Study The Nephrotoxicity And Hepatotoxicity Of Melamine (cyanuric Acid) To Newborn Rat And Adult Rat

BACKROUND: Melamine is a nitrogen-containing heterocyclic triazine compound. It is an important organic chemical raw material. Since mid-March 2007, More than 4000 cats, dogs and other pet were poisoned by pet food in United States. FDA investigation showed that recall pet food, dead animals, urine crystals and renal cells had found melamine and cyanuric acid. University of Guelph study found that melamine and cyanuric acid could produce crystallization which can damage kidney function. Melamine contaminated milk powder caused a significant public health event which aroused wide attention at home and abroad in China in 2008. The babies and infants who ate contaminated baby milk powder were easy to urinary calculi, renal dysfunction, and severe cases eventually lead to renal failure. Until now besides powdered milk, candy, cookies, eggs and other food products also contaminated by melamine which were reported. Melamine hydrolysis when it meets strong acid or alkali solution, amino is gradually replaced by hydroxy, generate cyanuric acid diamide, further hydrolyzed cyanuric an amide, and finally generate cyanuric acid. Cyanruic acid is a derivate of melamine. It is also a nitrogen-containing heterocyclic triazine compound. It commonly used herbicides, dyes, resins, pool disinfectants, etc and closely linked with people's daily life and work. The melamine, cyanuric acid, melamine-cyanuric acid mechanisms and the possible long-term complications, and there was no safe and effective intervention, in-depth study.OBJECTIVE: Study the acute, chronic toxicity of melamine (cyanuric acid ) to newborn SD rats, young SD rats and adult rats , see the kidney damage and interfere the damage.METHOD: 21 broods 7-day-old newborn SD rats, 8 broods 20-day-old young SD rats and 132 adult SD rats were selected. Divided the 21 broods 7-day-old newborn SD newborn rats and 84 adult rats into high dose group of melamine (NM, M), low dose group of melamine (Nm, m), high dose group of cyanuric acid (NA, A), low dose group of cyanuric acid (Na, a), high dose group of melamine-cyanuric acid (NMA, MA), low dose group of melamine-cyanuric acid (Nma, ma) and normal control group (NN, N). The corresponding dose of melamine (cyanuric acid) was given by oral gavage everyday. Divided 8 broods 20-day-old young SD rats and 48 adult SD rats into the group of melamine-cyanuric acid treated with christina loosestrife (a, A), the group of melamine-cyanuric acid treated with citrate (b, B), the group of melamine-cyanuric acid treated with sodium bicarbonate (c, C), the group of melamine-cyanuric acid treated with tap water (d, D), melamine-cyanuric acid spontaneous recovery group (e, E) and normal control group (f, F). The spontaneous recovery group of young rats were 3 broods and adult rats was 18. The a group, A group, b group, B group, c group, C group,d group, D group, f group, F group were divided randomly.The same number of rats in model groups was killed after intragastric administration 3 days, 15 days and 60 days. The body weight, liver and kidney weight were collected. The convention biochemistry target of blood was examined. The liver and kidney histology change observed. The intervention groups were killed after intragastric administration 30 days. The same number of rats in spontaneous recovery group was killed after intragastric administration 15 days, 30 days and 60 days. The body weight and kindy weight were collected. The convention biochemistry target of blood was examined. The kidney histology change was observed. According to the number of renal calculus, we divided them into negative (–), weakly positive (+), positive (++) and strong positive (+++). Electron microscopy observed each group of rats'renal unit.RESULT: The body weight of NN group, NM group, Nm group NA group, Na group newborn rats increased continuously. NMA group and Nma group body weight first increased, and then decreased. The body weight of M group, m group, A group, a group adult groups increased gradually, and then maintained at a lever. The body weight of M group began to reduce nearly 60 days. The body weight of MA group and ma group reduced gradually. The number of the model groups'kidney crystal under anatomical microscope was that 3 days of NMA group was (+), 15 days (++), 60 days (+++); Nma group of 3 days and 15 days all were (–), 60 days (+++). NM group of 60 days was (+); the other newborn groups were (–) at each time points; 3 days of M group was (–), 15 days (+), 60 days (+++); m group of 3 days and 15 days were (–), 60 days (+); A group of 3 days and 15 days were (–), 60 days ( ++); a group of 3 days and 15 days were (–), 60 days (+); MA group of 3 days and 15 days were (+++); 3 days of ma group was (++), 15 days (+++); N group was (–). The electron microscope demonstrated that the tubules which contained stones microvilli reduced or disappeared, granulocyte infiltration and other inflammatory response. In the model groups, the kidney weight/body weight, urea nitrogen, creatinine, uric acid value increased in NMA group, Nma group, NM group, MA group, ma group, M group and A group with administration time extension; and the Nm group, NA group, Na group, m group, A group and a group were similar to control group. HE staining of liver, liver weight /body weight, serum alanine aminotransferase and aspartate aminotransferase values were not significantly abnormal in each group.The body weight of a group, b group, c group, d group, e group, f group increased continuously. The body weight of A, B, C, D group reduced gradually. E group body weight first decreased, and then increased. The body weight of F group increased continuously. The number of the intervention groups'kidney calculus under anatomical microscope was that the a group, b group, c group, d group, e group, f group and F group were (–);A group was (++); B group was (++); C group was (–); D group was (+); E group of 15 days was (+++), 30 days (+++), 60 days (++). A, B, F groups'kidney weight/body weight value was much higher than C, D, E group. The kidney weight/body weight value decreased with time extension.CONCLUSION: Melamine (cyanuric acid) could produce insoluble calculus in rat kidney and the number of melamine (cyanuric acid) calculus was positively correlated with dose and time. Melamine (cyanuric acid) can cause blood urea nitrogen, creatinine, uric acid levels rise, leading to renal dysfunction. The toxicity of melamine (cyanuric acid) was greater in adult rats than in newborn. The toxicity of melamine was greater than cyanuric acid. Melamine (cyanuric acid) mixture toxicity was greater than the monomer. Melamine (cyanuric acid) toxicity had individual differences and brood diffenences. Melamine (cyanuric acid) did not have significant liver toxicity. Melamine (cyanuric acid) calculus can be discharged slowly. Alkaline urine could help melamine (cyanuric acid) calculus discharged.