Hepatic Cytochrome P-450-Dependent Metabolism and Enzymatic Conjugation of Foreign Compounds in Vitamin A-Deficient Rats

Siddik, Zahid H.; Drew, Roger; Litterst, Charles L.; Mimnaugh, Edward G.; Šikić, Branimir I.; Gram, Theodore E.

doi:10.1159/000137457

Cited by 28 publications

(8 citation statements)

References 11 publications

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“…The observed diminution in he patic cytochrome P-450 content, cytochrome b5 levels, and activity of benzo(a)pyrene hy droxylase is in accordance with the earlier reports [2,3,12], Also the decrease in hepatic UDP-GT activity (phase II enzyme) is in agreement with the earlier findings [20]. However, information on the role of vitamin A deficiency in altering the pulmonary phase I and phase II enzymes is lacking.…”

Section: Discussionsupporting

confidence: 92%

Effect of Vitamin A Deficiency on the Pulmonary and Hepatic Drug-Metabolizing Enzymes in Rat

Sc¹,

Khanduja²,

Mp³

et al. 1983

Enzyme

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The effect of vitamin A deficiency on the drug-metabolizing enzyme system of the lung and liver was analyzed in rats fed diets with or without vitamin A for 5-6 weeks. The hepatic level of vitamin A was significantly reduced in vitamin A deficient animals. The hepatic cytochrome P-450 and b(5) contents and activity of benzo(a)pyrene hydroxylase was significantly reduced in deficient animals. Contrary to this, pulmonary cytochrome P-450 and b(5) contents were above the control values. No alteration in pulmonary benzo(a)pyrene hydroxylase was noted. The uridine diphosphate-glucuronosyltransferase activity of digitonin- treated microsomal membranes was below the control values both in lung and liver. However, the native uridine diphosphate-glucuronosyltransferase activity remained unchanged in the liver and was below control values in the lung.

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Section: Discussionsupporting

confidence: 92%

Effect of Vitamin A Deficiency on the Pulmonary and Hepatic Drug-Metabolizing Enzymes in Rat

Sc¹,

Khanduja²,

Mp³

et al. 1983

Enzyme

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“…Diminished intestinal UDPGT activity in vitamin A-deficient ani mals may suggest that the glucuronidation potential of the intestinal mucosa is reduced in vitamin A deficiency and this effect be comes more pronounced when the deficient animals are exposed to AFB[. The observed increase in the GST activity in vitamin A deficiency is in agreement with earlier reports [17], The elevated GST levels following AFB | exposure observed in the present study is however a new finding, the significance of which is not clear from the study.…”

Section: Discussionsupporting

confidence: 90%

Intestinal Drug Metabolizing Systems (Phase I and Phase II) in Rats Fed Vitamin A-Deficient Diet and Aflatoxin B<sub>1</sub>

Nair¹,

Chauhan²,

Gupta³

et al. 1982

Digestion

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The combined effect of vitamin A deficiency and aflatoxin-B₁ (AFB₁) on the biphasic xenobiotic biotransformation status of the intestinal mucosa was studied in male weanling rats receiving vitamin A-deficient diet and AFB₁ for 42 days. The findings indicate that the mucosal aminopyrine-N-demethylase and p-nitroanisole O-demethylase representing the mixed function oxidase activity is significantly increased in the gut by the end of 42 days. Of the phase II enzymes studied, UDP-glucuronyl transferase showed a significant decrease, while the glutathione S-transferases and mucosal glutathione showed significant increase. The observations suggest that in vitamin A deficiency, the intestinal xenobiotic metabolism is grossly altered and this effect appears to be further amplified in the concurrent AFB₁ exposure.

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“…Siddik et al (31) have also reported increased activity of this enzyme accompanied by decreased cytochrome P-450. The increased UDPG transferase of lungs seems to be in part due to low food consumption whereas that of liver may be solely attributed to membrane damage.…”

Section: Discussionmentioning

confidence: 88%

Drug metabolism in experimental tuberculosis: I. Changes in hepatic and pulmonary monooxygenase activities due to infection

Batra

Venkitasubramanian

Raj

1987

European Journal of Drug Metabolism and Pharmacokinetics

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Pulmonary and hepatic drug metabolizing enzyme activities of tuberculous guinea pigs were examined in detail. Experimental tuberculosis resulted in enlargement of liver and lung accompanied by decreased microsomal cytosolic protein. The tuberculosis infection resulted in decreased hepatic contents of cytochrome P-450 and cytochrome b5 NADPH-cytochrome C reductase in lung and liver. A parallel decrease in the microsomal mixed function oxidases (MFO) was observed in liver and lung of tuberculous guinea pigs. The hepatic and pulmonary activities of UDP-glucuronyl transferase were elevated in the infected animals. Glutathione S-transferase activity exhibited an increase in liver and decrease in the lung of tuberculous guinea pigs. Some of the changes observed in monooxygenase in tuberculosis were caused by reduced food consumption. In general, tuberculosis infection can be viewed to lower drug metabolizing capacity of the animal, probably due to the damage and disturbed membrane integrity.

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Hepatic Cytochrome P-450-Dependent Metabolism and Enzymatic Conjugation of Foreign Compounds in Vitamin A-Deficient Rats

Cited by 28 publications

References 11 publications

Effect of Vitamin A Deficiency on the Pulmonary and Hepatic Drug-Metabolizing Enzymes in Rat

Effect of Vitamin A Deficiency on the Pulmonary and Hepatic Drug-Metabolizing Enzymes in Rat

Intestinal Drug Metabolizing Systems (Phase I and Phase II) in Rats Fed Vitamin A-Deficient Diet and Aflatoxin B<sub>1</sub>

Drug metabolism in experimental tuberculosis: I. Changes in hepatic and pulmonary monooxygenase activities due to infection

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