title: Chronic trimethyltin chloride exposure and the development of kidney stones in rats.
abstract: 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.
authors.affiliation: Department of Epidemiology and Environmental Health, the State University of New York, Buffalo, USA; Department of Pharmacology and Toxicology, the State University of New York, Buffalo, USA; Guangdong Medical Laboratory Animal Center, Foshan, Guangdong, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Ren
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.forename: Gang
authors.initials: G
authors.lastname: Sui
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Gong
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Yawson
authors.forename: Banghua
authors.initials: B
authors.lastname: Wu
authors.forename: Guanchao
authors.initials: G
authors.lastname: Lai
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Ruan
authors.forename: Hongbin
authors.initials: H
authors.lastname: Gao
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Bing
authors.initials: B
authors.lastname: Su
authors.forename: James R
authors.initials: JR
authors.lastname: Olson
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007669:Kidney Calculi / Q000139:chemically induced / Q000473:pathology*; D017616:Magnesium Compounds / Q000633:toxicity / Q000652:urine; D008297:Male; D010710:Phosphates / Q000633:toxicity / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D000069877:Struvite; D014298:Trimethyltin Compounds / Q000633:toxicity* / Q000652:urine; D014961:X-Ray Diffraction
chemical_list: D017616:Magnesium Compounds; D010710:Phosphates; D014298:Trimethyltin Compounds; C040533:trimethyltin chloride; D000069877:Struvite
keywords: H+/K+-ATPase; kidney stone; nephrotoxicity; reproductive/developmental toxicity; trimethyltin chloride