Journal
JOURNAL OF APPLIED TOXICOLOGY
Volume 35, Issue 5, Pages 500-507Publisher
WILEY
DOI: 10.1002/jat.3054
Keywords
H+; K+-ATPase; kidney stone; nephrotoxicity; reproductive; developmental toxicity; trimethyltin chloride
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Funding
- National Natural Science Foundation of China [30771786, 30972458]
- Guangdong Natural Science Foundation [S2012030011009]
- State University of New York, Buffalo
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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 mu gkg(-1)day(-1). Transient behavioral changes were observed in the high-dose group during the first 2weeks 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 mu gkg(-1)day(-1) dose group and 3 out of 9 rats in the 131.3 mu gkg(-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 6H(2)O, 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. Copyright (c) 2014 John Wiley & Sons, Ltd. We previously reported that occupational trimethyltin (TMT) exposure is a risk factor for developing kidney stones. Here we performed a 180-day animal study and showed that chronic TMT exposure can significantly inhibit the activity of renal H+/K+-ATPase and subsequently lead to an increase in urinary pH. We observed a dose-dependent increase in the incidence of kidney/urinary tract stones and the pathological changes in the kidneys of rats with TMT exposure compared with the rats in the control group.
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