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

• Published in: Journal of applied toxicology Vol. 35; no. 5; pp. 500 - 507
• Main Authors: Ren, Xuefeng, Wu, Xin, Sui, Gang, Gong, Zhihong, Yawson, Emmanuel, Wu, Banghua, Lai, Guanchao, Ruan, Xiaolin, Gao, Hongbin, Zhou, Feng, Su, Bing, Olson, James R., Tang, Xiaojiang
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.05.2015; Wiley Subscription Services, Inc
• Subjects: Animals; Chlorides; Dose-Response Relationship, Drug; Exposure; Female; Gas Chromatography-Mass Spectrometry; H+/K+-ATPase; Hydrogen-Ion Concentration; Kidney - drug effects; Kidney - pathology; Kidney Calculi - chemically induced; Kidney Calculi - pathology; kidney stone; Kidney stones; Kidneys; Magnesium Compounds - toxicity; Magnesium Compounds - urine; Male; nephrotoxicity; Occupational hazards; Phosphates - toxicity; Phosphates - urine; Rats; Rats, Sprague-Dawley; reproductive/developmental toxicity; Risk; Risk factors; Rodents; Stone; Struvite; Toxicity; trimethyltin chloride; Trimethyltin Compounds - toxicity; Trimethyltin Compounds - urine; Urinary tract; X-Ray Diffraction; reproductive/developmental toxicity; H+/K+-ATPase; nephrotoxicity; trimethyltin chloride; kidney stone
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.3054

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. Copyright © 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.