Cisplatin neurotoxicity: failure to demonstrate vitamin B12 inactivation.
Cisplatin binds in vitro with vitamin B12 coenzymes at physiologic pH and temperature. We have hypothesized that cisplatin-induced neurotoxicity is due to an in vivo inactivation of the cobalamin coenzymes. Vitamin B12 metabolism was studied in patients treated with cisplatin for advanced cancer. Serum levels of B12 and B12-binding capacity remained normal during cisplatin therapy. Excessive urinary excretion of methylmalonic acid and homocystine, which are both metabolic correlates of cellular cobalamin deficiency, was not demonstrated after cisplatin administration. Thus, we find no evidence to implicate cellular B12 deficiency as a mechanism of cisplatin neurotoxicity.
D000704:Analysis of Variance; D002940:Circadian Rhythm; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D003038:Cobamides / Q000378:metabolism; D005260:Female; D006710:Homocysteine / Q000097:blood / Q000652:urine; D006801:Humans; D007263:Infusions, Parenteral; D008764:Methylmalonic Acid / Q000652:urine; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism; D014805:Vitamin B 12 / Q000378:metabolism*; D014806:Vitamin B 12 Deficiency / Q000139:chemically induced*
D003038:Cobamides; D006710:Homocysteine; D008764:Methylmalonic Acid; D014805:Vitamin B 12; D002945:Cisplatin