Ethanol influence on insulin secretion from isolated rat islets

This study was done to delineate the role of alpha- and beta-adrenergic receptors and cyclic AMP in the mechanism of ethanol effects on insulin release from isolated islets. Rats were given an alpha-adrenergic blocker, phentolamine, or a beta-adrenergic blocker, propranolol. In addition, ethanol 1 g/kg was given intragastrically 1 h prior to sacrifice. Glucose mediated insulin release from isolated islets was enhanced by phentolamine and decreased by propranolol. Ethanol treatment inhibited glucose-induced insulin release from isolated islets of control rats as well as those given phentolamine and/or propranolol. Insulin release from isolated islets in response to dibutyryl-cyclic AMP was attenuated by ethanol. Theophylline enhanced glucose mediated insulin release from control islets but ethanol treatment produced a significant inhibition of insulin response. The data suggest that the site of action of the deleterious effects of ethanol on insulin release from isolated islets in rat does not involve adrenergic system and cyclic AMP.     

Effect of ethanol intake on phenytoin metabolism in volunteers.

Ingestion of ethanol, 1 g/kg, did not influence the phenytoin half-life in 5 volunteers after single i.v. administration of 3 mg/kg phenytoin. The control phenytoin half-life was 12.4 h (SD +/- 4.4); with ethanol ingestion it was 12.3 h (SD +/- 5.2).     

Dexamethasone protection against the acute lethality of ethanol in mice

Summary The administration of dexamethasone (DXM, 2.00 mg/kg) 1 h prior to the injection of lethal doses of ethanol was found to offer complete protection against ethanol toxicity at doses up to 5.25 g/kg and partial protection using higher doses. It is suggested that DXM central action might be involved in the protection against ethanol toxicity.Supported by a grant from U.S. National Aeronautics and Space Administration.     

Covalent binding of aflatoxin B1 to liver DNA in rats pretreated with ethanol

Male Fischer F-344 rats were given ethanol in the drinking water and/or by single oral administration. Following this, the animals received p.o. 100 ng/kg of the hepatocarcinogen [3H]aflatoxin B1 (AFB1). 24 h later, the level of DNA-bound AFB1 was determined in the liver and was found not to be affected by any type of ethanol pretreatment. A cocarcinogenic effect of ethanol in the liver is therefore unlikely to be due to an effect on the metabolic activation inactivation processes governing the formation of DNA-binding AFB1 metabolites.     

Ethanol influence on insulin secretion from isolated rat islets

Summary This study was done to delineate the role of - and -adrenergic receptors and cyclic AMP in the mechanism of ethanol effects on insulin release from isolated islets. Rats were given an -adrenergic blocker, phentolamine, or a -adrenergic blocker, propranolol. In addition, ethanol 1 g/kg was given intragastrically 1 h prior to sacrifice. Glucose mediated insulin release from isolated islets was enhanced by phentolamine and decreased by propranolol. Ethanol treatment inhibited glucose-induced insulin release from isolated islets of control rats as well as those given phentolamine and/or propranolol. Insulin release from isolated islets in response to dibutyryl-cyclic AMP was attenuated by ethanol. Theophylline enhanced glucose mediated insulin release from control islets but ethanol treatment produced a significant inhibition of insulin response. The data suggest that the site of action of the deleterious effects of ethanol on insulin release from isolated islets in rat does not involve adrenergic system and cyclic AMP.Supported by the U.S. Veterans Administration     

Diurnal rhythm of ethanol metabolism in the rat

Male Sprague-Dawley rats injected with 2.0 g/kg of ethanol and analyzed 1 h later at 8 specific times of the day showed diurnal rhythms for alcohol concentrations in the blood, urine, brain and liver tissues. The circadian fluctuation noted for the concentrations of blood and tissue ethanol might indicate a diurnal variation in the enzymatic metabolism of ethanol.     

Diurnal rhythm of ethanol metabolism in the rat

Summary Male Sprague-Dawley rats injected with 2.0 g/kg of ethanol and analyzed 1 h later at 8 specific times of the day showed diurnal rhythms for alcohol concentrations in the blood, urine, brain and liver tissues. The circadian fluctuation noted for the concentrations of blood and tissue ethanol might indicate a diurnal variation in the enzymatic metabolism of ethanol.Supported by a grant from the US National Aeronautics and Space Administration.     

Covalent binding of aflatoxin B1 to liver DNA in rats pretreated with ethanol

Summary Male Fischer F-344 rats were given ethanol in the drinking water and/or by single oral administration. Following this, the animals received p.o. 100 ng/kg of the hepatocarcinogen [³H]aflatoxin B₁ (AFB₁). 24 h later, the level of DNA-bound AFB₁ was determined in the liver and was found not to be affected by any type of ethanol pretreatment. A cocarcinogenic effect of ethanol in the liver is therefore unlikely to be due to an effect on the metabolic activation and inactivation processes governing the formation of DNA-binding AFB₁ metabolites.To whom correspondence should be addressed.Acknowledgment. We thank the European Science Foundation for the Toxicology Research Fellowship awarded to M.M.     

Time course study of the changes in blood glutathione induced by acute ethanol intoxication in the rat

Acute ethanol treatment of rats (5 g/kg) has a biphasic effect on the glutathione content of the erythrocyte. After 3 h of intoxication there is a diminution in total GSH equivalents, followed by a recovery to basal values 6 h after treatment. The decrease of total GSH equivalents is mainly due to a diminution of the oxidized form of the tripeptide. Concomitantly a marked increase in the plasma level of glutathione was found at 3 h, followed by a diminution to values obtained at time zero.     

Possible role of intestinal alkaline phosphatase activity in thiamine transport.

Thiamine deficiency caused a marked decrease of intestinal alkaline phosphatase (al-Pase) activity, but had no effect on the Ca++-ATPase activity and Ca++-absorption in rats. The al-Pase activity was significantly decreased 1 h after oral administration of ethanol at 0.5 and 2.5 g/kg. In contrast, Mg++-, Ca++-and (Na+ + K+)-ATPase activities did not change after the administration of ethanol. These findings show that the al-Pase activity, unlike the Ca++-ATPase activity, is not related to Ca++-absorption. A possible role of al-Pase activity in the active transport of thiamine in the intestine was discussed.     

Lowering of liver acetaldehyde but not ethanol concentrations by pretreatment with taurine in ethanol-loaded rats

A rise in blood and liver acetaldehyde concentrations following ethanol loading (1.5 g/kg b.wt) was significantly reduced when rats were pretreated orally with taurine (0.5 g/kg), a potent in vitro activator of yeast aldehyde dehydrogenase. This taurine pretreatment produced a 4-fold increase in liver taurine content.     

The influence of peripheral or central administration of ondansetron on stress-induced gastric ulceration in rats

Ondansetron (0.08, 0.15 or 0.3 mg/kg) injected s.c., every 12h with the fourth dose given 0.5 h before experiments, dose-dependently lessened gastric glandular mucosal ulceration produced by cold-restraint stress for 2h. When given intracerebrally (i.c.) (0.1, 0.5 or 1g), using the same treatment regimen, infusion of ondansetron 1 g into the nucleus amygdaloideus centralis decreased stress-evoked ulcers; in contrast, injection of the same dose into the nucleus accumbens intensified these lesions. The associated stress-induced stomach wall mast cell degranulation was unaffected by all s.c. or i.c. doses of ondansetron. Pretreatment with disodium cromoglycate i.p. alone, or concurrently with ondansetron s.c., prevented not only ulceration but also mast cell degranulation. 5-Hydroxytryptamine₃ receptor antagonism appears to inhibit stress-evoked ulcers mainly by blocking the peripheral effects of the amine after its release from the gastric mucosal mast cells.     

Lowering of liver acetaldehyde but not ethanol concentrations by pretreatment with taurine in ehtanol-loaded rats

Summary A rise in blood and liver acetaldehyde concentrations following ethanol loading (1.5 g/kg b.wt) was significantly reduced when rats were pretreated orally with taurine (0.5 g/kg), a potent in vitro activator of yeast aldehyde dehydrogenase. This taurine pretreatment produced a 4-fold increase in liver taurine content.     

Enhancement of ethanol-induced sleep by whole oil of nutmeg

In young chickens, the whole oil of nutmeg (200 mg/kg) increased the duration of sleep induced by ethanol (1--4 g/kg), particularly deep sleep. Iproniazid (50-400 mg/kg), a monoamine oxidase inhibitor, did not mimic this effect.     

Protection of rat gastric mucosa against ethanol injury by the new synthetic prostaglandin MDL 646

Summary Oral administration to fasted rats of absolute ethanol produces extensive necrotic lesions of gastric mucosa as well as a massive leakage of proteins and mucus glycoproteins into gastric lumen. When the new synthetic prostaglandin MDL 646, belonging to the PGE₁ series, is administered intragastrically (2 or 10 g/kg) 30 min before ethanol administration, a significant protection of rat gastric mucosa against alcohol injury is observed.This work was supported in part by a contribution from Ministero della Pubblica Istruzione (MPI), Rome, Italy.     

Effect of desipramine on the contents of some free amino acids of mouse brain

Summary I.p. injections of desipramine-HCL (100 mg/kg) produced decreases in the contents of several amino acids of mouse brain after 1 h. Using a 10–100 mg/kg range of doses, these effects appeared to be dose-dependent for -alanine and aspartate. These changes may be due, in part, to a decrease in cerebral oxidative metabolism (Krebs cycle activity) which occurs secondarily to desipramine-induced hypothermia.This study was supported by Centro Ramón y Cajal and Fundacion Juan March.     

Possible role of intestinal alkaline phosphatase activity in thiamine transport

Summary Thiamine deficiency caused a marked decrease of intestinal alkaline phosphatase (al-Pase) activity, but had no effect on the Ca⁺⁺-ATPase activity and Ca⁺⁺-absorption in rats. The al-Pase activity was significantly decreased 1 h after oral administration of ethanol at 0.5 and 2.5 g/kg. In contrast, Mg⁺⁺-, Ca⁺⁺- and (Na⁺+K⁺)-ATPase activities did not change after the administration of ethanol. These findings show that the al-Pase activity, unlike the Ca⁺⁺-ATPase activity, is not related to Ca⁺⁺-absorption. A possible role of al-Pase activity in the active transport of thiamine in the intestine was discussed.     

Enhancement of ethanol-induced sleep by whole oil of nutmeg

Summary In young chickens, the whole oil of nutmeg (200 mg/kg) increased the duration of sleep induced by ethanol (1–4 g/kg), particularly deep sleep. Inproniazid (50–400 mg/kg), a monoamine oxidase inhibitor, did not mimic this effect.Acknowledgments. The authors would like to thank Mr E.J. Spellman of Frische-D & O for supplying the oil of nutmeg and Mrs N. Sherry for secretarial and editorial assistance.     

Bombesin promotes pancreatic growth in suckling rats

Summary The pancreatic growth promoting effect of long term administration of bombesin was investigated in suckling rats. The authors showed that bombesin given in 10 g/kg b.wt doses s.c. every 8 h for 10 days from the day of parturition stimulated pancreatic growth: it increased pancreatic weight, protein and DNA content, trypsin and amylase activity and trypsin/DNA ratio. Conclusion: Bombesin is an effective stimulator of pancreatic growth in suckling rats.     

Influence of repeated prazosin administration on cardiovascular responses in rats and rabbits

Prazosin was injected i.v. at a dose of 50 g/kg every 2 h for 8 h in conscious rats. Its hypotensive action significantly declined. A similar effect was also observed in rabbits pretreated with prazosin (40 g/kg, i.v.) every 1 h for 4 h. In prazosin-treated rabbits, the total peripheral resistance became less responsive to phentolamine stimulation. Repeated prazosin administration abolished its ability to block receptors in a model of anococcygue muscle contraction after noradrenaline (NA) stimulation. The -adrenoceptors in anococcygue muscle exhibited lower pD₂ to NA and lower pA₂ to prazosin in prazosin-treated rats. The results demonstrate that repeated prazosin administration reduces the effectiveness of -adrenoceptors blockers.