Evaluation of the cytoprotective effect of cow's milk against ethanol-induced gastrointestinal toxicity in albino rats: immunohistochemical and histopathological studies

ABSTRACT

Ethyl alcohol [ethanol] is readily absorbed from all parts of the gastrointestinal [GI] tract due to its hydrophilic potential. Its biological effects in human refer to practically every organ and system. The exposure of gastric and small intestinal mucosae to ethanol produces pathological changes such as inflammatory process, hemorrhagic erosions, and even acute ulcers. Although several studies have shown that milk protein components have a wide range of biological activities, the potential role of these proteins in the GI mucosal defense system is less well elucidated. In this study, we detected the GI lesions induced by short-term oral administration of ethanol to adult albino rats, after 2 and 4 weeks. Furthermore, the protective ability of milk against these injuries was determined. The morphological damage in the stomach and small intestine was detected by histopathological examination while apoptosis [programmed cell death] in the GI mucosal cells induced by ethanol, could be detected by immunohistochemical [IHC] method using Bcl-2 protein expression in the cells. This study was carried out on 60 albino rats divided into 3 equal groups as follows [1] Control group [received water and basic diet], [2] Ethanol group received a daily oral dose of 5ml/Kg b. w. of 50% ethanol [10[th] of the LD50], [3] Milk + Ethanol group [milk 500 mg/Kg was orally given one hour before the same dose of ethanol as in the 2[nd] group]. After 2 weeks of ethanol administration the gastric and intestinal mucosal injuries were detected histopathologically and apoptotic changes by Bcl-2 expression were moderate, whereas after 4 weeks these lesions induced by ethanol were increased in severity and accompanied by a strong expression of Bcl-2 protein which pointed to severe apoptosis [group 2]. These findings indicate that ethanol-induced GI apoptosis which is influenced by the duration of exposure. This study also showed that when animals were pretreated with milk before ethanol [group 3] there was a markedly reduction in the occurrence of GI lesions after 2 weeks and even after 4 weeks in which only mild apoptosis was detected by weak Bcl-2 protein expression. It can be concluded that milk has marked antiulcer activity and may serve to protect the GI mucosa against injuries induced by ethanol