Research On The Cinnabar-induced Subchronic Renal Toxicity And Its Mechanism In Rats

ObjectiveTo explore the cinnabar-induced subchronic renal toxicity and itsmechanism in rats by oral administration.Methods32healthy SD rats were randomly divided into control group and cinnabargroup, each made up of16, half male and half female. The cinnabar group ratswere administrated orally with1.0g/kg/d cinnabar in0.5%carboxymethylcellulose sodium solution for12weeks, and the control group was given thesame volume of solvent. During the administration, the situation in rats such asmental status, daily food intake, daily water intake, coat color, feces, andactivities were observed. The rats were weighed once a week.24h urine of halfof rats in each group were collected after repeated dosing8and12weeks, andthe animals were sacrificed the next day and blood and kidney samples werecollected. The mercury content in the blood and the kidney were determined byhydride generation atomic fluorescence spectrometry, and the mercury contentin the urine was determined by hydride generation atomic absorptionspectrophotometry. The concentrations of serum and urine creatinine weremeasured, and the creatinine clearance were also computed. The content ofAlpha1microglobulin (α1-MG) and Kidney injury molecule-1(KIM-1) weretested by ELISA. The kidney slice were observed under light microscopes andtransmission electron microscopes (TEM). Apoptotic cells of kidney weredetected by TUNEL. The cytokines related to apoptosis in kidney were detectedby Biotin Label-based Rat Antibody Array1. The data were analyzed withSPSS17.0, using independent sample t tests to compare between the twogroups, significance level was α=0.05. ResultsDuring the administration, the general condition of rats from the two groupswere normal and their body weight were steadily grown. After being dosedcinnabar for8and12weeks, the content of mercury in urine, blood and kidneyfrom the treated rats were higher than that from the control (P<0.05). After8wand12w, the levels of urine α1-MG and KIM-1in cinnabar group weresignificantly increased (P<0.05). Under the light microscopy, the kidney tissue ofcinnabar group rats was infiltrated by inflammatory cell, vacuolar degeneration,protein casts and apoptosis. Apoptosis was confirmed by TUNEL and TEM inthe kidney tissue of the cinnabar group, and apoptotic index was significantlyhigher, the difference was statistically significant (P<0.01) after8w and12w.Compared with the control group, the expression of Activin A, Adiponectin, FasL,Fas, TNF-alpha, TRAIL in the cinnabar group significant increased, and thedifference was statistically significant (P <0.05).ConclusionsLong-term or overdose of cinnabar could cause mercury accumulation inthe kidney and lead to kidney damage. Cinnabar could induce apoptosis of renaltubular epithelial cells in the cortex, and which might be a significant mechanismof cinnabar-induced kidney damage. Death receptor-mediated apoptosissignaling pathway may be an important way of cinnabar-induced cell apoptosisin renal tubular epithelial.