Protective effects of α-hederin, chlorophyllin and ascorbic acid towards the induction of micronuclei by doxorubicin in cultured human lymphocytes

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Abstract
The influence of α-hederin (a saponin isolated from Hedera helix), chlorophyllin, the sodium-copper salt of chlorophyll, and ascorbic acid (vitamin C) on the direct clastogenicity of doxorubicin (Adriamycin®) was investigated in vitro in human lymphocytes for the induction of micronuclei. In order to determine a possible mechanism of action responsible for the antimutagenic activity, treatments were performed for the three substances at different times of the culture (pre-treatment, simultaneous and post-treatment). Alpha-hederin (1.3×10−2, 0.13, 1.3 and 13 nmol/ml) and chlorophyllin (0.14, 1.4 and 14 nmol/ml) were found to exert an antimutagenic effect against the clastogenicity of doxorubicin (1.5×10−2 nmol/ml) in all treatments at all concentrations. Ascorbic acid (10 nmol/ml) was effective in reducing the micronucleus levels only in the simultaneous treatment, when it was previously incubated with doxorubicin for 2 h at 37°C before being introduced into the culture. Our results suggested a desmutagenic effect for α-hederin, chlorophyllin and ascorbic acid. Chlorophyllin acted also through a bio-antimutagenic mechanism and a-hederin seemed to induce metabolic enzymes, which inactivated doxorubicin. Preliminary studies showed sthat the effective antimutagenic concentrations of α-hederin, chlorophyllin and ascorbic acid had no clastogenic or aneugenic effects in human lymphocytes. No cytotoxicity was observed for the three antimutagenic agents either.

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