Tiopronin protects against the nephrotoxicity of cisplatin in the rat

1 Tiopronin (N-(2-mercaptopropionyl)-glycine) is a drug with a free thiol ( sulphydryl) group that is used clinically. We have reported previously that tiopronin protects rat kidney slices in vitro from the nephrotoxic effects of cisplatin and does not reduce the antitumour activity of cisplatin, Tio pronin has been investigated therefore for its protective effects in rats i n vivo. 2 The extent of kidney damage was studied 5 days after the administ ration of cisplatin. A single injection (i.p.) of cisplatin (6 mg/kg; 20 mu mol/kg) to female Wistar albino rats caused a sustained decrease in body w eight and, after 5 days, plasma urea, creatinine and kidney weight were inc reased. Tiopronin (2.5 mmol/kg, p.o.) ameliorated cisplatin nephrotoxicity when given 1 h before cisplatin. Tiopronin provided marked protection again st cisplatin-induced increases in urea (from 237+/-19 mg to 48+/-23 mg/100 ml; control: 17+/-1) and creatinine (from 6.5+/-0.5 to 1.7+/-0.5 mg/100 ml control: 1.0+/-0.1). Tiopronin did not, prevent the bo dy weight loss cause d by cisplatin. In addition, an intraperitoneal dose (1 mmol/kg) of tiopron in afforded similar protection to that of an oral dose. Rats that received an i.p. mixture of cisplatin (6 mg/kg) and tiopronin (65 mg/kg) displayed g enerally less toxicity, as indicated by a small fall in body weight and sma ller increases in urea and creatinine and kidney weight. 3 The results show that tiopronin protects against cisplatin-induced nephrotoxicity. Oral adm inistration of tiopronin may be a clinically useful way to prevent cisplati n nephrotoxicity.