Inhibitory effect of Emblica officinalis on the in vivo clastogenicity of benzo[a]pyrene and cyclophosphamide in mice.
Benzo[a]pyrene (B[a]P) and cyclophosphamide (CP) are potent carcinogens/mutagens. Effect of Emblica officinalis extract administration on the in vivo genotoxicity of B[a]P and CP was studied using bone marrow chromosomal aberration and micronucleus induction tests in mice. Three doses (50, 250 and 500 mg/kg body weight) of the plant extract were administered orally for 7 consecutive days prior to the administration of single dose of mutagens (B[a]P 125 mg/kg oral; CP 40 mg/kg i.p.). It was found that administration of 250 and 500 mg/kg of E. officinalis extract significantly inhibited the genotoxicity of B[a]P as well as CP in both the assay systems. Administration of 50 mg/kg of the plant extract had no inhibitory effect. Vitamin C, a major constituent of E. officinalis when administered at dose level of 9 mg/kg b.w. (the approximate estimated amount present in the highest dose of plant extract, i.e. 500 mg) for 7 days did inhibit chromosomal aberrations and micronuclei induction, but not in a significant manner. Effect of administration of the abovementioned effective doses (250 and 500 mg/kg oral for 7 days) of plant extract and vitamin C (9 mg/kg oral for 7 days) on the hepatic activation and detoxification enzymes was also studied. Significant induction in the levels of glutathione content (GSH) and of antioxidant and detoxification enzymes viz., glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S transferase (GST) resulted from plant extract treatment to animals. On the other hand, cytochrome P 450 level was significantly decreased in the plant-extract-treated animals. There was no significant change in cytochrome P 450, GSH contents and activities of enzymes on treatment with vitamin C. The data indicate that the possible mechanism of inhibition by plant extract is mediated by its modulatory effect on hepatic activation and disposition processes.
Sharma
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N
Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110 062, India.
Trikha
P
P
Athar
M
M
Raisuddin
S
S
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects*; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects*; D003520:Cyclophosphamide / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D016296:Mutagenesis / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity*; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal
D016587:Antimutagenic Agents; D009153:Mutagens; D010936:Plant Extracts; D001564:Benzo(a)pyrene; D003520:Cyclophosphamide; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D001205:Ascorbic Acid