Role of calcium in modulation of toxicities due to cisplatin and its analogs: a histochemical approach.
Cisplatin, carboplatin and paclitaxel (taxol) are potent antineoplastic agents with associated toxicities, especially gastrointestinal and nephrotoxicity that are their dose-limiting factors in clinical oncology. In an attempt to elucidate their mechanism(s) of toxicity, liver and kidney tissues from normal and drug treated rats and dogs were evaluated for changes in various dehydrogenase and non-specific lipase enzymes. Histochemically, cisplatin treatment induced an inhibition of all the enzymes studied except glucose-6-phosphate dehydrogenase and non-specific lipases, where there was a significant increase. Supplemental treatments with calcium [1 ml of 1.3% CaCl2/day in rats and 2.50 mg (150000 USP units) ergocalciferol plus 1000 mg of elemental calcium as TUMS 500 (EffeCal)/day in dogs] seem to protect against severe gastrointestinal toxicity and nephrotoxicity.
Meara
D J
DJ
Department of Zoology, Michigan State University, East Lansing 48823-1115, USA.
Johnson
B
B
Wang
Y
Y
Aggarwal
S K
SK
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000097:blood / Q000494:pharmacology*; D002945:Cisplatin / Q000633:toxicity*; D002952:Citric Acid Cycle / Q000187:drug effects; D004285:Dogs; D004347:Drug Interactions; D004872:Ergocalciferols / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D006651:Histocytochemistry; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008049:Lipase / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D004872:Ergocalciferols; D000255:Adenosine Triphosphate; D010088:Oxidoreductases; D008049:Lipase; D002117:Calcitriol; D002945:Cisplatin; D002118:Calcium