Effect of cisplatin and 6-bromo-6-deoxy-L-ascorbic acid on some biochemical and functional parameters in mice

The results of the present study demonstrate that 6-bromo-6-deoxy-L-ascorbi c acid (6-BrAA), an antioxidative derivative of ascorbic acid, is capable o f lowering the toxicity of cisplatin, cis-diaminedichloroplatinum (cis-DDP) , an anticancerogenic drug. The biological aspects and pharmacological sign ificance of a combined treatment of these two substances were investigated in a mouse model. The results indicate that the effectiveness of 6-BrAA on biological response(s) is strongly dependent on the dose of cis-DDP. Inject ion of 10 mg/kg body weight (bw) of cis-DDP following pretreatment with 6-B rAA (480 mg/kg bw) enhances the tissue-protecting effect of 6-BrAA and redu ces, to some extent, the ensuing nephro-, liver and spleen toxicity. On the other hand, 6-BrAA in animals treated with a higher dose of cis-DDP (15 mg /kg bw) leads to exacerbation of the toxic cis-DDP effect and concurrent lo ss of the protective potential of 6-BrAA with respect to tissue damage. The exact mechanism(s) of 6-BrAA protection and exacerbation of the toxic cis- DDP effect is unclear, although scavenging or generating of free radicals m ay play an important role. The results obtained may be of importance in pla nning the rational use of cis-DDP and 6-BrAA administration in the potentia l treatment of cancer. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.