Amelioration of cisplatin toxicity in rat renal cortical slices by dithiothreitol in vitro.
1. The protective effects of dithiothreitol (DTT) on cisplatin-induced nephrotoxicity were investigated with rat renal cortical slices. 2. The nephrotoxic effects of cisplatin (2 mmol l-1) were manifested in several ways: the Na+ and water content were increased while K+ was decreased. The malondialdehyde (MDA) concentration in the slices and the lactate dehydrogenase (LDH) released into the medium were increased. The uptake of p-aminohippurate (PAH), the synthesis of glucose and the glutathione (GSH) concentration in the slices were all decreased. 3. Despite a DTT-related increase in platinum (Pt) uptake by the slices, DTT (0.5-2 mmol l-1) ameliorated all these toxic effects of cisplatin in a concentration related manner. 4. The results suggest that the protective mechanism of DTT is its antioxidative action. DTT is also a metal chelator, however, and so a protective effect via chelation of Pt by DTT cannot be excluded.
Zhang
J G
JG
Department of Toxicology, Dalian Medical College, People's Republic of China.
Zhong
L F
LF
Zhang
M
M
Ma
X L
XL
Xia
Y X
YX
Lindup
W E
WE
D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D004229:Dithiothreitol / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D010984:Platinum / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D014867:Water / Q000378:metabolism; D010130:p-Aminohippuric Acid / Q000378:metabolism
D014867:Water; D010984:Platinum; D012964:Sodium; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D002945:Cisplatin; D011188:Potassium; D004229:Dithiothreitol; D010130:p-Aminohippuric Acid