Effects of phenobarbital and sodium salicylate on cytochrome P-450 mixed function oxygenase and glutathione S-transferase activities in rat brain

Recent evidence has suggested that the endogenous antipyretic arginine vasopressin (AVP) may participate in drug-induced antipyresis. This study sought to further those investigations by comparing the effects of two other antipyretic drugs, sodium salicylate and acetaminophen, administered intraperitoneally, during AVP V1-receptor blockade within the ventral septal area (VSA) of the rat brain. During endotoxin-evoked fever, V1-receptor blockade within the VSA of the conscious unrestrained rat significantly antagonized the antipyretic effects of salicylate. The effects of the V1-antagonist on salicylate-induced antipyresis were dose related. In contrast, the antipyresis elicited by acetaminophen was unaffected by VSA V1-antagonist pretreatment. Neither saline nor the V1-antagonist microinjected into the VSA of febrile or nonfebrile rats had any significant effects on the normal progression of endotoxin fever or normal core temperature, respectively. These data suggest that the mechanism of action of salicylate-induced antipyresis includes activation of AVP V1-type receptors within the VSA, as has been shown for indomethacin. However, the lack of effect of the V1-antagonist on antipyresis induced by acetaminophen indicates that not all antipyretic drugs act through the same mechanism in the brain.

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Induction of rat UDP-glucuronosyltransferase and glutathione S-transferase activities by L-buthionine-S,R-sulfoximine without induction of cytochrome P-450

Toxicology ◽

10.1016/0300-483x(90)90085-u ◽

1990 ◽

Vol 65 (1-2) ◽

pp. 149-159 ◽

Cited By ~ 16

Author(s):

Bradford W. Manning ◽

Michael R. Franklin

Keyword(s):

Glutathione S Transferase ◽

Udp Glucuronosyltransferase ◽

Cytochrome P 450

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Temperature Influence on Basal Activity and Induction of Mixed Function Oxygenase Activity in Fundulus heteroclitus

Journal of the Fisheries Research Board of Canada ◽

10.1139/f79-200 ◽

1979 ◽

Vol 36 (11) ◽

pp. 1400-1405 ◽

Cited By ~ 66

Author(s):

John J. Stegeman

Keyword(s):

Cytochrome C ◽

Fundulus Heteroclitus ◽

Reductase Activity ◽

Control Fish ◽

Cytochrome C Reductase ◽

Nadph Cytochrome ◽

Pyrene Hydroxylase ◽

Mixed Function Oxygenase ◽

Cytochrome P 450 ◽

Nadph Cytochrome C Reductase

Treatment of Fundulus heteroclitus acclimated to 6.5 °C with benzo(a)pyrene did not elicit any change in the levels of hepatic microsomal NADH- or NADPH-cytochrome c reductase activity, nor in the levels of cytochrome P-450 or its catalytic activities. However, the same treatment offish at 16 5 °C resulted in a marked induction of benzo(a)pyrene hydroxylase and NADPH-cytochrome c reductase. Cytochrome P-450 content was also higher in the warm, treated fish and the Soret maximum of reduced, CO-treated microsomes was shifted to the violet. Levels of aminopyrine demethylase and NADH-cytochrome c reductase activities did not show a significant treatment effect. At neither temperature could treated and control fish be distinguished on the basis of in vitro inhibition of benzo(a)pyrene hydroxylase activity by 7,8-benzoflavone. Levels of NADPH-cytochrome c reductase and benzo(a)pyrene hydroxylase activities were greater in control Fundulus acclimated to 6.5 °C than to 16.5 °C, when normalized to microsomal protein, but not when based on body weight. The results indicate that habitat temperature alone may not affect the capacity for initial hydrocarbon metabolism in fish, but that it can strongly influence the induction of cytochrome P-450. Key words: temperature, cytochrome P-450, hydrocarbon metabolism, mixed-function oxygenase, Fundulus heteroclitus

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