Chronic trimethyltin chloride exposure and the development of kidney stones in rats.

We recently reported that occupational exposure to trimethyltin (TMT) is a risk factor for developing kidney stones. To further examine the association between TMT exposure and the formation of kidney stones, we conducted a 180-day animal study and exposed the randomly grouped Sprague-Dawley (SD) rats to TMT in the drinking water at doses of 0, 8.2, 32.8 and 131.3 µg kg(-1) day(-1). Transient behavioral changes were observed in the high-dose group during the first 2 weeks of exposure. TMT exposure led to a significant dose-dependent inhibition of renal H(+)/K(+)-ATPase and an increase in urinary pH. In comparison to no kidney stones being identified in the control and the lowest dose group, 1 rat in the 32.8 µg kg(-1) day(-1) dose group and 3 out of 9 rats in the 131.3 µg kg(-1) day(-1) dose group were found to have stones in the kidney/urinary tract. Pathological analysis showed that more wide spread calcium disposition was observed in kidneys of rats with TMT exposure compared with the rats in the control group. However, X-ray diffraction (XRD) analysis found that the kidney stones were mainly composed of struvite with the formula: NH4MgPO4 6H2O, while calcium-containing components were also detected. Together, this study further demonstrates through animal studies that chronic exposure to a relatively low level of TMT induces nephrotoxicity and increases the risk for developing kidney stones.

[Study on activities and protein and gene expression of renal H(+)-K(+)-ATPase in rats subchronic exposed to trimethyltin chloride].

OBJECTIVE: To study the activity, protein and gene expression of renal HK-ATPase (HKA) in rats subchronic exposed to trimethyltin chloride (TMT). METHODS: In subchronic toxic test (14-week), 55 female SD rats (age, 6 weeks) were divided randomly into 5 groups: control, low, medium, high and super high dosage, respectively, which drank water with TMT of 0, 8.20, 32.81, 131.25 and 262.50 microg x kg(-1) x d(-1) for 14 weeks. Then serum K+ levels were measured; the activities of HK-ATPase (HKA) in kidneys were detected by the method of determinated phosphorus content; Western Blot assay and real-time PCR were used to exam the protein and mRNA expression levels of HKA in kidneys, respectively. RESULTS: The serum K+ level in super-high dosage group was (5.6 +/- 0.4) mmol/L, which was significantly lower than that [(6.9 +/- 0.3) mmol/L] in control group (P < 0.01). The HKA enzymatic activity of kidneys in low and super high dosage groups was 4.50 +/- 1.45 and 4.55 +/- 0.72 micromolPi x mg prot(-1)h(-1), respectively, which were significantly lower than that (6.55 +/- 0.77 micromol Pi x mg prot(-1) h(-1)) in control group (P < 0.05). CONCLUSION: When rats were exposed subchronic to TMT, the renal HKA activity could reduce, but the expression levels of HKA protein and mRNA did not decrease.

Studies on hypokalemia induced by trimethyltin chloride.

OBJECTIVES: To determine the possible relationship between plasma potassium concentration and severity of acute trimethyltin chloride (TMT) poisoning and to assess the mechanism of TMT induced hypokalemia. METHODS: SD rats were treated with various dosages of TMT (i.p.). All the indices were measured and analysed for determining their possible relations with plasma K+. RESULTS: With increase of dosage, the plasma K+ level dropped rapidly, and deaths appeared more quickly. The LD50 of TMT (i.p.) was 14.7 mg/kgbw. In the low dosage group (10 mg/kgbw), the plasma K+ level dropped slowly with the lowest dosage on day 6 (4.85 mmol/L). It rose again on day 11 (5.06 mmol/L), and recovered on day 28. The poisoning signs corresponded with decline of the span of K+ level. The plasma Na+ level dropped half an hour after TMT treatment, but recovered 24 h later. In the high dosage group (46.4 mg/kgbw), the levels of plasma K+ and Na+ fell rapidly within half an hour (P < 0.05), the intracellular potassium concentration of RBC did not decrease obviously (P > 0.05), the activities of Na(+)-K(+)-ATPase and Mg(2+)-ATPase in RBC membrane were depressed remarkably (P < 0.01, P < 0.05, respectively), the plasma aldosterone concentrations rose as high as tenfold (P < 0.01), the arterial blood pH fell from 7.434 to 7.258 (P < 0.01), pCO2 was raised from 29.62 to 45.33 mmHg (P < 0.01). In the 24 h urine test, when rats were treated with TMT (21.5 mg/kgbw, i.p.), urine volume, urinary potassium, sodium and chloride increased significantly in comparison with those in the controls (P < 0.01). CONCLUSION: TMT could induce hypokalemia in SD rats. The available evidence suggests that TMT can induce acute renal leakage of potassium. At the same time, a significant rise of plasma aldosterone may play an important role in promoting potassium leakage from kidney to result in severe hypokalemia with inhaling acid-base abnormalities produced, which aggravate the poisoning symptoms. In the end the rats would die of respiratory failure.