engleski

Effect of 6-bromo-6-deoxy-L-ascorbic acid on cisplatin-induced toxicity in mice

The biological aspects and pharmacological significance of combined treatment of 6-bromo-6-deoxy-ascorbic acid (6-BrAA) and cis-diaminedichloroplatinum (cis-DDP)in mice model are investigated. The results indicate that effectiveness of 6-BrAA on biological response(s) is sharply dependent on the dose of cis-DDP. The treatment with lower dose of cis-DDP (10mg/kg bw)and pretreatment with 6-BrAA (480mg/kg bw) 2 h before cis-DDP contribute to the tissue protecting effect of modulating agent reducing in some extent the nephro-liver-and spleen toxicity. The blood nitrogen urea level and the lipid peroxidation process delected as thiobarbituric reactive substances (TBARS) were significantly lower (p 0.01 and p 0.05, respsctively), while liver lysosomal membrane permeability and total sialic acid content in spleenocytes did not attained statistical significance compared to cis-DDP treated mice. On the other hand, 6-BrAA in animals treated with higher dose of cis-DDP (15 mg/kg bw) leads to exacerbation on the toxic cis-DDP effect and concurrent loss of protective potential of the 6-BrAA toward tissue damage. Also, a significant decrease in protein concentration (p 0.05) in comparision to untreated as well as cis-DDP treated mice was observed. The exact mechanism(s) of 6-BrAA protection and exacerbation of the toxic cis-DDP effect is unclear, thhough scaveging or generating of free radicals may play an important role. The results obtained may be of importance in planing the rational use of cis-DDP and 6-BrAA administration in the potential treatment of cancer.

6-bromo-6-deoxy-L-ascorbic acid; cisplatin; mice

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