TOXICOLOGICAL EVALUATION OF THE NEUROENDOCRINOLOGIC, PANCREATIC AND HEPATIC EFFECTS OF BACLOFEN IN ALCOHOL DEPENDENT ALBINO RATS

Abstract

Alcohol is a toxic substance to cells and tissues. Chronic alcohol consumption damages the brain, liver and many other
organs like pancreas. Recently, new lines of treatment that maintain abstinence and preventing relapse to alcohol have
been escalated like baclofen and acamprosate. Baclofen is a GABAB receptor analog recently used as an effective
substitution drug. The aim of the current work was to evaluate the neuroendocrinologic, pancreatic and hepatic effects
of baclofen treatment in alcohol dependent albino rats from the toxicological point of view. Thirty adult male albino rats
were divided into 4 groups, Group 1: control rats: 12 rats equally subdivided into 1-a: negative control and 1-b: positive
control (n=6), daily received distilled water by gavage. Group 2: Baclofen group: Six rats gavaged baclofen 7.5mg/kg/d
for 3 days then, 15 mg/kg for the remaining of 4 weeks, Group 3: Ethanol group: Six rats gavaged ethanol 2.5 g/kg/d for
4 weeks, Group 4: Ethanol and baclofen group: Six rats gavaged ethanol 2.5 g/kg/d for 4 weeks, then received baclofen
(7.5 mg/kg/d in the first 3 days and 15 mg/kg/d), for the remaining of 4 weeks. All rats were investigated by assessment
of prolactin, leptin, ALP, ALT, AST, bilirubin, GGT, amylase and lipase serum levels, with histopathological
examination of the brain, pancreas and liver. It was found that baclofen induced a significant decrease in the mean
values of prolactin and leptin (P<0.05), with a significant increase in amylase (P<0.05), lipase (P<0.001), ALP,
(P<0.01), bilirubin (P<0.001), ALT (P<0.001) and GGT (P<0.05), without any hisolopathological changes, as compared
with +ve control group. Ethanol dependent rats showed a significant increase in the mean values of prolactin and leptin
hormones levels, amylase, lipase, ALP, bilirubin, AST, ALT, and GGT (P<0.001) with severe alteration of the normal
architecture of the brain, pancreas and liver. The alcohol dependent rats treated with baclofen showed a significant
increase in the mean values of serum amylase, lipase, ALP, bilirubin, AST, ALT, and GGT (P<0.01), with a non
significant decrease in the prolactin and leptin levels (P>0.05). However the biochemical changes were significantly
less than those of alcohol, the hisopathological changes in both groups were similar. It was concluded that baclofen
induced functional pancreatic and hepatic toxic changes in normal rats. Moreover, the functional and structural toxic
effects of chronic alcohol dependence on the brain tissues, pancreas and liver were almost similar, after 4 weeks of the
baclofen administration therapy. Further studies were recommended regarding the toxic effects of baclofen with a
special concern to the molecular mechanisms underlying such effects.
Keywords: Ethanol toxicity, alcohol dependence, baclofen, prolactin, leptin, liver function tests, amylase.