EFFECTS OF CHRONIC INTAKE OF ETHANOL ON RATE OF ETHANOL METABOLISM: II. INFLUENCE OF SEX AND OF SCHEDULE OF ETHANOL ADMINISTRATION

1967 ◽  
Vol 45 (5) ◽  
pp. 777-785 ◽  
Author(s):  
J. M. Khanna ◽  
H. Kalant ◽  
G. Bustos

Groups of adult Wistar rats were treated for up to 2 months with ethanol in a total daily dose of 9–12 g/kg, according to one of three different schedules of administration: (a) gavage, with a gradual stepwise increase in dosage, plus additional ethanol in the drinking water; (b) inclusion of ethanol in a liquid diet, with 36% of the calories as ethanol; (c) gavage with large intoxicating doses from the beginning of the experiment. Control animals received equicaloric amounts of sucrose in place of ethanol. Both male and female rats were used in schedule a, but only males in b and c. All three groups showed significant increases in liver alcohol dehydrogenase activity, and males and females responded alike. The increase was smallest and the variations greatest on schedule c. Liver lactic dehydrogenase activity was not affected, except for a decline during the first 2 weeks on schedule c, when the animals lost weight. When pair-feeding was used (schedule b), there was identical weight gain by the alcohol and control groups.

1980 ◽  
Vol 186 (2) ◽  
pp. 483-490 ◽  
Author(s):  
Gloria Rachamin ◽  
J. Alain Macdonald ◽  
Samina Wahid ◽  
Jeremy J. Clapp ◽  
Jatinder M. Khanna ◽  
...  

In young (4-week-old) male and female spontaneously hypertensive (SH) rats, ethanol metabolic rate in vivo and hepatic alcohol dehydrogenase activity in vitro are high and not different in the two sexes. In males, ethanol metabolic rate falls markedly between 4 and 10 weeks of age, which coincides with the time of development of sexual maturity in the rat. Alcohol dehydrogenase activity is also markedly diminished in the male SH rat and correlates well with the changes in ethanol metabolism. There is virtually no influence of age on ethanol metabolic rate and alcohol dehydrogenase activity in the female SH rat. Castration of male SH rats prevents the marked decrease in ethanol metabolic rate and alcohol dehydrogenase activity, whereas ovariectomy has no effect on these parameters in female SH rats. Chronic administration of testosterone to castrated male SH rats and to female SH rats decreases ethanol metabolic rate and alcohol dehydrogenase activity to values similar to those found in mature males. Chronic administration of oestradiol-17β to male SH rats results in marked stimulation of ethanol metabolic rate and alcohol dehydrogenase activity to values similar to those found in female SH rats. Chronic administration of ethanol to male SH rats from 4 to 11 weeks of age prevents the marked age-dependent decreases in ethanol metabolic rate and alcohol dehydrogenase activity, but has virtually no effect in castrated rats. In the intoxicated chronically ethanol-fed male SH rats, serum testosterone concentrations are significantly depressed. In vitro, testosterone has no effect on hepatic alcohol dehydrogenase activity of young male and female SH rats. In conclusion, in the male SH rat, ethanol metabolic rate appears to be limited by alcohol dehydrogenase activity and is modulated by testosterone. Testosterone has an inhibitory effect and oestradiol has a testosterone-dependent stimulatory effect on alcohol dehydrogenase activity and ethanol metabolic rate in these animals.


1966 ◽  
Vol 44 (2) ◽  
pp. 241-257 ◽  
Author(s):  
Rosemary D. Hawkins ◽  
H. Kalant ◽  
J. M. Khanna

In two separate studies of 6 and 12 weeks duration, adult male rats of the Wistar strain received ethanol in a total daily dose of about 9 g/kg. Growth rate was the same as that of glucose-treated controls. In comparison with controls of comparable weight, ethanol-treated rats showed significant increases in liver alcohol dehydrogenase (LAD) activity at all times after the first 2 weeks, but no significant change in catalase activity. The rate of disappearance of ethanol from the blood after a test dose was also significantly increased in the chronically treated rats, and the increase was initially comparable to that found in LAD activity. Later, the rate of ethanol disappearance rose more than could be explained by increased LAD activity. Normal male rats showed higher liver catalase activity than did normal females, but did not differ in LAD activity, which was higher at 9–10 weeks of age than in older or younger animals. It is suggested that failure of some investigators to find an alcohol-induced increase in LAD activity may be due to different responses by males and females.


1976 ◽  
Vol 54 (6) ◽  
pp. 539-545 ◽  
Author(s):  
G. W. Forsyth ◽  
H. T. Nagasawa ◽  
C. S. Alexander

Rat hearts perfused with oxygenated buffer containing [1-14C]ethanol metabolized small amounts of the ethanol to carbon dioxide. Very sensitive techniques are required to separate the resulting 14CO2 from the ethanol. This metabolism is not inhibited by levels of pyrazole which markedly inhibit NAD dependent liver alcohol dehydrogenase (EC 1.1.1.1). In vitro studies suggest that NADP functions as a cofactor for the rat heart alcohol dehydrogenase activity of crude heart homogenates. The kinetic parameters, the specific activity, and the pH dependence of the enzyme activity measured in these experiments suggest that it may have a minor role in ethanol metabolism by the rat.


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