Modulation of the impaired drug metabolism in sarcoma-180-bearing mice by echitamine chloride.
Echitamine chloride (EC), an indole alkaloid, extracted from the bark of Alstonia scholaris has got highly promising anticancer effect. The effect of this drug on the microsomal drug detoxifying system was studied in sarcoma-180 induced mice. When given sub-cutaneously at a dosage of 5 mg/kg body weight, it was able to alter the impaired drug detoxifying system which was observed in the Sarcoma-180 bearing mice. The levels of microsomal protein, Cyt-P450, Cyt-b5, NADH-Cyt-C-reductase, NADPH-Cyt-C-reductase, and glu-6 phosphatase were determined. The levels of these drug metabolizing enzymes were decreased in S-180 bearing mice. EC treatment corrected to near normal levels of these enzymes and microsomal hemeproteins. In order to understand the mechanism responsible for the decreased protein level and its normalization after treatment with EC, 3H-Phenylalanine incorporation study was carried out. From the results, it is observed that the synthesis of apoproteins is also altered in tumor-bearing animals. All these changes which were observed in tumor-bearing animals were corrected to near normal levels after treatment with EC.
Saraswathi
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V
Department of Biochemistry, University of Madras, Guindy Campus, Chennai.
Mathuram
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V
Subramanian
S
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Govindasamy
S
S
D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001059:Apoproteins / Q000096:biosynthesis / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D015786:Cytochromes b5 / Q000235:genetics / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D004790:Enzyme Induction / Q000187:drug effects; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism*; D006420:Hemeproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008658:Inactivation, Metabolic; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000378:metabolism
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D001059:Apoproteins; D006420:Hemeproteins; D009363:Neoplasm Proteins; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; D009245:NADH Dehydrogenase; D005952:Glucose-6-Phosphatase; C001133:echitamine