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Biomedical subjects

I D Capel

Publications and source records attributed to I D Capel.

33 records · Page 2Linked to original sources

The effect of isolation stress on some hepatic drug and carcinogen metabolising enzymes in rats.

Rats were subjected to stress by isolation for periods of up to eight days, which produced an elevation in plasma cortisol. In vivo drug metabolism as estimated by the plasma elimination rate of orally-administered antipyrine was not significantly affected by this treatment although there was an apparent decrease in the absorption rate of the drug. In vitro experiments on hepatic microsomal preparations derived from stressed animals indicate that this stress increased in the activity of some enzyme systems concerned with benzo(a)pyrene activation and this correlated with an increased binding of the carcinogen to DNA. The activity of conjugating enzyme which could catalyze the excretion of such carcinogens was not significantly altered. The results indicated that stress could have an important bearing on carcinogenesis by enhancing to a greater extent enzyme systems responsible for activation than those involved in the excretion of polycyclic aromatic hydrocarbons.

Animals↗

Correlation between tumour size, metastatic spread and galactosyl transferase activity in cyclophosphamide-treated mice bearing the Lewis lung carcinoma.

Galactosyl transferase activity was measured in tumour and normal tissues of mice receiving cyclophosphamide treatment for Lewis lung carcinoma. Animals which responded to cyclophosphamide therapy had significantly smaller tumours with fewer metastases than the untreated mice. The level of galactosyl transferase was significantly reduced in the tumours which were inhibited by the cyclophosphamide treatment.

Animals↗

Hepatic function assessed (in rats) during chemotherapy with some anti-cancer drugs.

Using rats, we studied how best to assess hepatic damage after administering therapeutic doses of each of five anti-cancer drugs or of the hepatotoxin, carbon tetrachloride. As indexes, we compared measurement of the concentration of administered antipyrine in plasma with measurement in serum of alpha-fetoprotein or of the activities of five enzymes that reportedly best reflect hepatic damage. The biological half-life of antipyrine in the plasma was increased more than threefold on pretreating the rats with any of the five cytotoxic drugs or with carbon tetrachloride. In contrast, the concentrations of alpha-fetoprotein, alkaline phosphatase, gamma-glutamyltransferase, or glutamate dehydrogenase were not consistently increased. Of the enzymes tested in serum, aspartate aminotransferase and ornithine carbamoyltransferase best indicated hepatic impairment resulting from the treatment with anti-cancer drugs. Our results imply that determination of the pharmacokinetics of marker drugs such as antipyrine better indicates hepatic dysfunction induced by cytotoxic agents than does measurement of the enzymes liberated into serum as a result of damage to liver mitochondria.

Alkaline Phosphatase↗

The effect of chronic alcohol intake upon the hepatic microsomal carcinogen-activation system.

Ethanol was administered to mice either by repeated intraperitoneal injection, or orally in the drinking water over an extended period of time. Following intraperitoneal ethanol pre-treatment further groups of mice received an injection of benzo(a)pyrene. Alcohol intake decreased the level of microsomal aryl hydrocarbon hydroxylase which corresponded to the observed decrease in DNA binding of benzo(a)pyrene. In contrast, the number of tumors which developed in the alcohol pre-treated mice exceeded those of the control animals.

Administration, Oral↗

The effect of chronic ethanol intake on the growth and spread of some murine tumors.

The effect of chronic ethanol intake on the growth and spread of some murine tumors has been investigated. The treatment had no effect on the B 16 melanoma but tended to decrease the number of Ehrlich ascites cells. In the case of the Lewis lung carcinoma, administration of ethanol for two weeks tended to lower the number of metastases to the lung without significantly affecting the primary tumor size, whereas more prolonged ethanol intake decreased the weight of the primary tumor in addition to decreasing its dissemination.

Alcoholism↗

Vitamin E retards the lipoperoxidation resulting from anticancer drug administration.

The administration of either 5-fluorouracil, methotrexate, cyclophosphamide or vincristine to rats produced an increase in liver and plasma, but not brain, lipoperoxide levels. There was no significant difference between the glutathione peroxidase activity in the liver and the brain tissue of cytotoxic drug-treated and control rats. Glutathione peroxidase activity was significantly lower in the erythrocytes of 5-fluorouracil-and methotrexate-treated rats than in control animals. The erythrocyte glutathione peroxidase levels of vincristine- and cisplatin-treated rats did not differ significantly from the control levels. Rats which received vitamin E supplementation concomitantly with 5-fluorouracil treatment had liver and plasma lipoperoxide levels which were significantly lower than those which had received only the anticancer drug. The tissue lipoperoxide levels in the vitamin E supplemented, 5-fluorouracil-treated rats were comparable with those of arachis oil-treated controls.

Animals↗