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

• Published in: Toxicology (Amsterdam) 1999-09, Vol.137 (1), p.23-34
• Main Authors: Šverko, Višnja, Radačić, Marko, Gavella, Mirjana, Lipovac, Vaskrsenija, Ljubenkov, Ivan, Eckert-Maksić, Mirjana
• Format: Article
• Language: English
• Subjects: 6-Bromo-6-deoxy-l-ascorbic acid; Acid Phosphatase - blood; Acid Phosphatase - drug effects; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Ascorbic Acid - analogs & derivatives; Ascorbic Acid - pharmacology; Biological and medical sciences; Blood Urea Nitrogen; cis-Dichlorodiamineplatinum; Cisplatin - toxicity; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Female; Lipid peroxidation; Lipid Peroxidation - drug effects; Liver - drug effects; Liver - enzymology; Liver - metabolism; Lysosomes; Medical sciences; Mice; Mice, Inbred CBA; Miscellaneous (drug allergy, mutagens, teratogens...); N-Acetylneuraminic Acid - metabolism; Pharmacology. Drug treatments; Sialic acid; Thiobarbituric Acid Reactive Substances - metabolism; Time Factors
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/S0300-483X(99)00069-4

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.