Effect Of Long-term Exposure To Carbon Disulfide On The Kidney Of Rats

Objective: To observe the damage of long-term exposure to carbon disulfide(CS2) on the kidney of rats through the detection of urine index, serum biochemical index, kidney pathology morphological changes, the apoptosis and expression of Bax in the nephrocyte, and investigate the possible mechanism, to provide laboratory information on prevention and treatment of CS2 poisoning. Methods: Take 80 healthy SD male rats to be randomly divided into five groups after being fed adaptively for a week, normal group, blank group(0 mg/kg), and low CS2 exposure group(50 mg/kg), middle CS2 exposure group(150 mg/kg), and high CS2 exposure group(250 mg/kg), by intraperitoneal injection for 16 weeks, 5d/w, 1/d. Each group of animals is to have normal diets and free to drink water, weighed every week at the fixed time and the dosage is adjusted correspondingly according to the weight change.. At the end of 12 th and 16 th weekend, 6 rats are taken from each group to collect 24 h urine, the urinary protein, urine creatinine and urine N-acetyl-β-D-gluosaminidase(NAG) were tested. After killing them, blood is collected through heart to test its serum biochemical index. The kidney index is calculated based on the kidney tissue sample from each rat(The calculationformula: kidney weight / body weight), Pathological changes of paraffin sections of renal tissue specimens with hematoxylin- eosin(HE) staining are observed by light microscope; the percentage of nephrocyte apoptosis is measured by TUNEL method and Bax expressions in the renal tissue are detected by Immunohistochemical method. Results:(1) With the CS2 exposure time extending, the animals gradually develop muscles relaxation, muscle tension reduce, the abnormal gait and other symptoms,which signal the CS2 toxic damage.(2) At the 12 th and 16 th weekend, body weight, kidney index, urine creatinine and urine NAG level in the mid-dose and the high-dose group rats were change significantly(P<0.05), and urine NAG level in the low-dose group rats were increased significantly compared with the normal group and the blank group(P<0.05). Among the three exposure groups, the high-dose group were change significantly compared with the low-dose group(P<0.05), and urine NAG level in the high-dose group is increased distinctively compared with the mid-dose group(P<0.05).(3) At the 16 th weekend, compared with the normal group and blank group, the SCr and BUN level of the high-dose group and the mid-dose group are increased significantly(P<0.05). Compared with the low-dose group, the high-dose group is increased(P<0.05), but the mid-dose group change is not obvious(P>0.05). At the 12 th weekend, the change of the SCr and BUN level are not obvious(P>0.05). At the 12 th and 16 th weekend, compared with the normal group and blank group, the AST, TC, TG level in the high-dose group are increased significantly(P<0.05), the AST levelin the mid-dose group are increased(P<0.05), and the AST level in the high-dose group is increased evidently comparing with the low-dose group(P<0.05).(4) HE staining shows that the tubular injury at the 12 th and 16 th weekend with the expanding CS2 exposure is exacerbated, and the pathological grading of the injured renal tubule in the high-dose group were higher than that of the normal group and the blank group(P<0.05).(5) Nephrocyte apoptosis percentages are increased with prolonged time and increased dosage, and nephrocyte apoptosis percentages of the CS2 exposure groups are evidently higher than that of the normal group and the blank group at the 12 th and 16 th weekend(P<0.05).(6) Immunohistochemical staining reveals that Bax protein shows brown in the cytolymph of the CS2 exposure group. With prolonged time and increased dosage, the staining is deepened and patchy distribution is expanded. Expressions of Bax in the normal group and the blank group are weak and scattered positive. Meanwhile, the number of positive cells in the CS2 exposure groups are accumulated gradually, and that of the high-dose and the mid-dose group are clearly higher than the normal group and the blank group(P<0.05). Conclusion:(1) Long-term exposure to CS2 can cause structural and functional renal damage of rats.(2) Apoptosis maybe one of the mechanism of renal damages causing by CS2.