Study On Renal Toxicity At Subchronic Lead Exposure In Rats

Objective To study the effects of renal damage at subchronic leadexposure in rats. Methods 42 young male SD rats were randomly assigned to one controlgroup and five lead-treated groups. Rats of control group were given deionizedwater by gavage. The lead-treated groups were given 6.25,12.5,25,50,100mg/Kg body weight lead acetate by gavage, respectively. All of thesetreatments were done once a day,5 days/week for 8 weeks.Then the rats weresacrificed and kidney obtained. The change in histology of kidney was observedunder light and electronic microscope. Urinary lead,urinary δ-Aminolevulinicacid(δ-ALA),urinary creatinine,urinary total protein(TP),urinary β₂-Microglubin(β₂-MG),urinary N-Acety-β-D-glucosamindase(NAG),superoxide dismutase(SOD),malondialdehyde(MDA),nitric oxide(NO)and nitric oxide synthase(NOS)were determined. Apoptosis of renal cells werecalculated by molecular biological methods. Results 1,There were significant increase of urinary lead and urinaryδ-ALA in lead-treated groups compared to control group (P<0.05).There wassignificant increase of the 8th week urinary lead and urinary δ-ALA compared tothe 4th week (P<0.01). Increased urinary lead and urinary δ-ALA were foundaccompanying with increased dosages of lead acetate. 2,There was significant increase of urinary TP,urinary β₂-MG ,urinaryNAG and kidney index in lead-treated group compared to control group.Increased urinary lead and urinary δ-ALA were found accompanying withincreased dosages of lead acetate. The levels of the experimental groups werehigher than the control group after 8 weeks.And the levels were significantlyincreased as the dose increased.In the light microscope,the lesions werelocalized in renal tubules. The damage degree was related to the poisoningdosage;Renal proximal tubular epithelial cells present swollen and turbid tovarious degrees with pathomorphological observation.The high-dose groupseven show focal necrosis.Submicroscopic structure changes include nucleuswithered,mitochondria swelling and the ridge obscured. 3,The rats were given lead acetate 8 weeks later,NOS,SOD activity andNO level decrease as the exposured dose increases.However the level of MDAincreases. The phenomena show that the molecular mechanism of kidney tissueoxidization damage might be related to the emergence of oxygen free radicalsinduced by lead. 4,The indexes of apoptosis in every group are clear difference by one wayANOVA.And the indexes increase as the expourse dose increases. Conclusions 1,The lead-induced renal damage may occur by gavagewith lead acetate.The animal model may further study the mechanism of leadrenal toxicity; 2,When the dose of exposure reach a special level,it induces not only the changes of renal function but also the organic damage; 3,The changes of the tissue fatty acid composition and the add of lipid peroxidation might be the mechanism of lead nephortoxicity; 4,Lead can induce apoptosis. And the structure and function of kidneycan be damaged by cell apoptosis. So cell apoptosis play an important role inthe mechanism of lead nephortoxicity.