Search PubMed⌕ Search

Biomedical subjects

A Aitio

Publications and source records attributed to A Aitio.

At least 109 records · Page 6Linked to original sources
PubMed1978

Responses of the D-glucuronic acid pathway in rat tissues to treatment with tetrachlorodibenzodioxin.

1. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was administered to rats to study its effects on the enzyme activities of the D-glucuronic acid pathway in the liver, small intestine and kidney. 2. The UDP-glucuronosyl transferase activity of male albino rats given TCDD (80 mug/kg, one dose, i.p.) 6 days before killing was significantly increased in all tissues examined, and UDP-glucuronic acid pyrophosphatase activity was markedly decreased in the liver. D-Glucuronolactone and L-gulonate dehydrogenase activities in the liver and small intestine were slightly decreased after TCDD treatment. 3. The activities of UDP-glucose dehydrogenase and beta-glucuronidase were unchanged. 4. The 24 h urinary excretion of L-ascorbic acid was enhanced 8-fold, although no difference was detected in the excretion of D-glucaric acid between the control and experimental animals. 5. These results suggest an increased capacity for glucuronide conjugation after treatment with TCDD. 6. The lack of increase in the urinary excretion of D-glucaric acid further challenges its use as a reliable indicator of enhanced drug metabolism.

Animals↗
PubMed1978

Effect of polybrominated biphenyls on drug metabolizing enzymes in different tissues of C57 mice.

Polybrominated biphenyls (PBBs) are structurally very close to polychlorinated biphenyls (PCBs) which are known to be potent inducers of xenobiotic biotransformation reactions. We have studied the effects of 2 industrial PBB-mixtures, "hexabromobiphenyl" (HBB) and "octabromobiphenyl" (OBB), on enzymes catalyzing drug hydroxylation, epoxide hydration, and conjugation reactions in different tissues of C57 mice. The enzyme activities were measured 10 days after a single i.p. injection of PBBs (75 mg/kg). HBB enhanced the activities of hepatic AHH (1.9-fold), ethoxycoumarin deethylase (5.7-fold), epoxide hydratase (1.5-fold), glutathione S-transferase (1.7-fold) and UDP-glucuronosyltransferase (1.5-fold). In the kidney HBB enhanced the activity of UDP-blucuronosyltransferase 1.5-fold. OBB caused in increase in the activities of liver AHH (1.5-fold), ethoxycoumarin deethylase (2.4-fold) and glutathione S-transferase (1.4-fold). A slight increase was also seen in the activity of UDP-glucuronosyltransferase in digitoninactivated liver microsomes of OBB-treated mice. In the kidney OBB caused a slight but statistically significant decrease in glutathione S-transferase activity. Intraperitoneally injected bromobiphenyls had no effects on these drug metabolizing enzymes in the lung of C57 mice. These results were similar to the effects caused by a mixture of PCBs.

Animals↗
PubMed1978

Effects of inhalation and cutaneous exposure to styrene on drug metabolizing enzymes in the rat.

The effects of inhalation and cutaneous exposure to styrene on the drug metabolizing enzymes were studied in the rat. Rats were exposed eight hours per day, for seven successive days to 450 ppm concentration of styrene or received one cutaneous dose of styrene daily for seven consecutive days (0.5 and 3.0 g/kg). The animals were killed one day after the last dose. Styrene inhalation increased the activities of epoxide hydrase and UDPglucuronosyltransferase (4-methylumbelliferone as substrate) in liver (1.5- and 1.7-fold, respectively). Ethoxycoumarin deethylation was enhanced 1.7-fold in the kidney. The content of cytochrome P-450 in the liver and the activities of NADPH cytochrome c-reductase, benzpyrene hydroxylase and glutathione S-transferase in the liver and kidney were not altered. No changes in the enzyme activities were detected in the lung. Styrene depressed the epoxide hydrase activity in liver when administered cutaneously. No signs of enzyme induction could be seen after cutaneous administration.

Administration, Topical↗
PubMed1978

Effect of phthalate esters on drug metabolizing enzyme activities in rat liver.

Dibutyl-, di(2-ethylhexyl)-, di(3, 3, 5-trimethylhexyl)- and didecylphthalate (DBP, DEHP, TMHP, DDP) all caused an increase in the amount of hepatic cytochrome P=450, when administered intragastrically to rats. No statistically significant increase could be detected in the catalytic activities dependent on cytochrome P-450 (Benzo(a)pyrene hydroxylation, ethoxycoumarin deethylation). Dibutylphthalate inhibited these reactions, when added to the incubation in vitro. Phthalates caused an increase in the activities of epoxide hydratase, and glutathione-S-transferase. Conjugation of 0-aminophenol and 4-methylumbelliferone with glucuronic acid was increased after phthalate administration.

Animals↗
PubMed1977

Neurochemical effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Wistar and Gunn rats.

Normal Wistar, heterozygous and homozygous Gunn rats were killed one week after a single intragastric dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 20 microgram/kg in acetone-olive oil. Control animals were treated similarly but without TCDD. The brain protein and RNA content were measured together with enzyme assays of lysosomal acid proteinase and soluble DT-diaphorase. Acid proteinase activity was increased in the brains of the normal Wistar rats after TCDD treatment. RNA and protein contents were lowered in the heterozygous Gunn rats whereas no changes were detected in the homozygous Gunn rats. The cerebral soluble DT-diaphorase activity was slightly enhanced (about 35%) by TCDD treatment only in normal Wistar rats. Our results may point at modified neurotoxic effects of TCDD in chronic exposure to bilirubin as in the case of Gunn rats.

Animals↗
PubMed1976

UDP glucuronosyltransferase and mixed function oxidase activity in microsomes prepared by differential centrifugation and calcium aggregation.

Microsomes were prepared from the liver, kidney and lung of phenobarbital or 20-methylcholanthrene treated and control rats with the conventional ultracentrifugation and calcium aggregation methods. The two methods were compared as to the yield of microsomal protein, amount of cytochrome P-450/448 and activity of UDP-GLUCURONOSYLTRANSFERASE, BENZOPYRENE HYDROXYLASE AND P-NITROANISOLE O-demethylase. The absolute amount of cytochrome P-450/448 (nmol/g wet weight), as well as the enzymatic activities dependent on it (nmol produced/g wet weight) did not differ significantly in any tissue of either treated or control animals nor did that of UDPglucuronosyltransferase. However, the ultracentrifugation method resulted in a slightly smaller yield of the hepatic microsomal protein and a correspondingly higher yield of cytochrome P-450/448 per mg protein as well as higher specific enzymatic activities of both the consecutive drug biotransformation reactions studied. The specific activity of UDPglucuronosyltransferase in digitonin treated microsomes was twice as high in the conventional microsomes as in the calcium aggregated microsomes; no differences was found in the trypsin treated microsomes. The specific activity of the hepatic benzpyrene hydroxylase of the benzpyrene treated animals in the calcium harvested microsomes was 55 per cent of that in the ultracentrifugated microsomes.

Animals↗