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-ascorbic acid (6-BrAA), an antioxidative derivative of ascorbic acid, is capable of lowering the toxicity of cisplatin, cis-diaminedichloroplatinum (cis-DDP), an anticancerogenic drug. The biological aspects and pharmacological significance 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. Injection of 10 mg/kg body weight (bw) of cis-DDP following pretreatment with 6-BrAA (480 mg/kg bw) enhances the tissue-protecting effect of 6-BrAA and reduces, 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 loss 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 may play an important role. The results obtained may be of importance in planning the rational use of cis-DDP and 6-BrAA administration in the potential treatment of cancer.
Sverko
V
V
Ruder Bosković Institute, Department of Molecular Medicine, Zagreb, Croatia.
Radacić
M
M
Gavella
M
M
Lipovac
V
V
Ljubenkov
I
I
Eckert-Maksić
M
M
D000135:Acid Phosphatase / Q000097:blood / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D000970:Antineoplastic Agents; D017392:Thiobarbituric Acid Reactive Substances; C068572:6-deoxy-6-bromoascorbic acid; D000135:Acid Phosphatase; D019158:N-Acetylneuraminic Acid; D001205:Ascorbic Acid; D002945:Cisplatin