Comparative alterations in extrahepatic drug metabolism by factors known to affect hepatic activity

Litterst, Charles L.; Mimnaugh, Edward G.; Gram, Theodore E.

doi:10.1016/0006-2952(77)90219-2

Cited by 58 publications

(7 citation statements)

References 17 publications

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“…Furthermore, kidney should be an important organ in biotransformation because under environmental conditions the uptake of pollutants occurs through the gills; then organic molecules are directed mainly to the kidney with arterial blood, whereas the major fraction of ip-injected xenobiotic compounds reach the liver where they are cleared by biliary elimination (Pesonen et al, 1987). A marked species difference exists in the induction of renal and hepatic monooxygenase activities in rodents (Lake et al, 1973;Litterst et al, 1977;Smith et al, 1986). In fish, similar discrepancies were also found.…”

Section: Resultsmentioning

confidence: 99%

Effect of β-naphthoflavone and MCPA on liver and kidney drug-metabolizing enzymes from the carp, Cyprinus carpio

Rivière

Devaux

Gonin

et al. 1990

Ecotoxicology and Environmental Safety

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The effects of fl-naphthoflavone (B-NF) and a chlorophenoxyacetic acid herbicide (MCPA) on hepatic and renal monooxygenase activities and conjugating enzymes from immature carp (Cyprinus carpio) were studied. j3-NF increased hepatic monooxygenase activities but the patterns of differential induction generally obtained in rat liver microsomes with two series of homologous substrates, alkoxycoumarins and alkylresomfins, were not found to be similar in carp liver microsomes. On the other hand, MCPA caused no changes in oxidative metabolism, with the exception of decreased aryl hydrocarbon hydroxylase activity. Renal activities were not modified by MCPA, while b-NF treatment resulted in marked increases in monooxygenase activities with alkylresorufins as substrates. No changes were found in conjugation activities after treatment with MCPA or P-NF. These results indicate that (a) the herbicide MCPA should have no effect on drug-metabolizing enzymes from carp, and (b) the hepatic and renal monooxygenase activities of carp are responsive to fl-NF, allowing their use in monitoring water pollution.

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Section: Resultsmentioning

confidence: 99%

Effect of β-naphthoflavone and MCPA on liver and kidney drug-metabolizing enzymes from the carp, Cyprinus carpio

Rivière

Devaux

Gonin

et al. 1990

Ecotoxicology and Environmental Safety

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“…Pretreatment with PBT or PCB had the expected effects [19,20] on rat liver hepatic and renal microsomal cytochrome-P-450 (Table II). In the liver, PBT and PCB caused 2-fold and 3-fold increases, respectively, in the level of cytochrome P-450.…”

Section: Resultsmentioning

confidence: 99%

Acute nephrotoxicity of 1,1-dichloroethylene in the rat after inhalation exposure

Jackson

Conolly

1985

Toxicology Letters

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A renal toxicity of 4 h inhalation exposure to 1,1-dichloroethylene (vinylidene chloride; VDC) was studied in male Sprague-Dawley rats. Kidney wt./body wt. ratios, serum urea nitrogen and creatinine levels were significantly increased 24 h after exposure to 250 ppm or more of VDC. Histopathologic examination by light microscopy of hematoxylin and eosin (H&E)-stained sections revealed severe tubular necrosis with calcium deposits at the higher exposure concentrations. Specific staining for calcium oxalate was negative, indicating that biotransformation of VDC to oxalate is probably not responsible for its nephrotoxicity. Pretreatment with polychlorinated biphenyl (PCB) induced the level of renal cytochrome P-450. Phenobarbital (PBT) pretreatment did not alter the renal P-450 level, but both PCB and PBT pretreatments antagonized VDC nephrotoxicity. These pretreatments have also been reported to antagonize VDC-induced hepatotoxicity. In summary, inhalation of VDC is nephrotoxic in the rat; the mechanism of nephrotoxicity does not involve calcium oxalate formation, and the magnitude of nephrotoxicity does not correlate directly with the total amount of renal cytochrome P-450.

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“…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. Carbontetrachloride induced liver injury has been reported to result in increased UDPG transferase activity (15) which is attributed to the liver damage thereby resulting in the release of this enzyme (32,33).…”

Section: Discussionmentioning

confidence: 99%

“…Microsomes and cytosol were prepared as described by Litterest et al (15). Protein in microsomes and cytosol was assayed according to the procedure of Lowry et al (16).…”

Section: Processing Of Tissuesmentioning

confidence: 99%

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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Comparative alterations in extrahepatic drug metabolism by factors known to affect hepatic activity

Cited by 58 publications

References 17 publications

Effect of β-naphthoflavone and MCPA on liver and kidney drug-metabolizing enzymes from the carp, Cyprinus carpio

Effect of β-naphthoflavone and MCPA on liver and kidney drug-metabolizing enzymes from the carp, Cyprinus carpio

Acute nephrotoxicity of 1,1-dichloroethylene in the rat after inhalation exposure

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

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