Evaluation of Hepatic Effect of Designed Regimen on Alcohol Induced Liver Injury In Wistar Rats

Abstract

INTRODUCTION: Alcohol is the leading cause of death as per the reports of the World Health Organization (WHO), (2018). Three million deaths occur because of excessive use of alcohol which accounts for around 5.3% of total deaths. Chronic and excessive consumption of alcohol leads to liver dysfunction characterized as steatosis, hepatitis, fibrosis, and cirrhosis. There is a lack of effective drugs to treat these diseases. In this study, we evaluated the combination of herbal drugs to treat liver damage and also to find out the possible mechanism related to its hepatoprotective. MATERIAL AND METHODS: In-vivo hepatoprotective activity was evaluated using adult Wistar rats. The study was carried out in two phases: - phase A (induction phase) and phase B (treatment phase). For the induction phase animals were divided into two groups: - Normal control (NC), and Disease control (DC). For the induction of hepatic injury ethanol (40%, 5gm/kg, p.o. for 6 weeks) was administered to animals. After 6 weeks of the induction period, animals were evaluated to assess the hepatic injury induction or not. The evaluation parameters were: - phenobarbitone-induced sleeping time, occult blood stool test, serum test SGPT, SGOT, and total bilirubin. After confirmation of liver injury the animals were divided into seven groups of five animal each: - Normal control (NC), Disease control (DC), Disease control + Milk (DC+M), Disease control + Shilajit +Milk (DC+SM), Disease control + Shilajit + Triphala (DC+ST), Disease control + Shilajit + Triphala + Milk (DC+STM), Disease control + Standard (DC+Std). According to the groups, the treatment was initiated in animals for 6 weeks with Shilajit (500mg/kg, p.o. with cow’s milk), and Triphala (400mg/kg, p.o. with cow’s milk). After 6 weeks of treatment, blood was collected for oxidative stress and histopathological evaluation. RESULTS: Treatment has significantly reduced the sleeping time of phenobarbitone-induced sleeping time in DC+STM group compared with DC group (p<0.01). A negative test with no blue color in occult blood stool test in DC+STM group was observed compared with a strong positive test with strong blue color in DC, and DC+M group. Serum SGPT level significantly decreases in DC+STM group compared with DC, (p<0.01) and DC+M group (p<0.05). Serum SGOT level significantly decreases in DC+STM group compared with DC, and DC+M group (p<0.01). Serum total bilirubin level significantly decreases in DC+SM, and DC+STM groups compared with DC group (p<0.01). Serum direct bilirubin level significantly decreases in DC+STM group compared with DC group (p<0.05). Serum ALP level significantly decreases in DC+STM group compared with DC group (p<0.01), also in DC+Std group compared with DC group (p<0.05). Serum total protein level significantly increases in DC+STM group compared to both DC, and DC+M groups (p<0.05). Serum albumin level significantly increases in DC+STM group compared with DC group (p<0.01). Serum CRP-Turbilatex level significantly decreases in DC+STM group compared with DC group (p<0.05). Restored levels of MDA, GSH, SOD, Catalase, and NO were found in liver, lungs, brain, heart, and kidney in DC+STM when compared with DC group (p<0.05). IL-6 level in liver tissue significantly decreases in DC+STM group compared with DC, and DC+M group (p<0.05). In Histopathology evaluation, DC+STM group showed regaining shape of central vein and improved cell size was observed compared with DC group. CONCLUSION: These findings indicate that the combination of shilajit and triphala with cow’s milk has improved the toxic signs of alcohol-induced liver injury which was reflected by restriction of various liver function parameters, reduced oxidative stress, and inflammation as well as improvement in liver architecture. However, further studies are required to establish a treatment.