Hepatoprotective Action of Dehydrozingerone in Carbon Tetrachloride and Thioacetamide-induced Hepatotoxicity in Wistar Rats

Abstract

© 2011, INASL 40 Synthesis and Antihepatotoxic Activity of 5-(2,3-dihydro-1,4-benzodioxane-6-yl)-3-substitutedphenyl-4,5-dihydro-1H-pyrazole Derivatives Habibullah*,**, B Ahmed** *Department of Pharmaceutical Chemistry, Alwar Pharmacy College, Alwar, Rajasthan **Antihepatotoxic Research Laboratory, Faculty of Pharmacy, Jamia Hamdard, New Delhi Background and Objective: Silymarin isolated from seeds of Silybum marianum commonly known as ‘milk thistle’ has been found most potent antihepatotoxic agent against a variety of toxicants. The Silymarin has been found to be a mixture of three isomers of flavonolignan i.e., silybin, silychristin and silydianin. The silybin is the most potent component containing 1,4-dioxan ring system. Other isomer silychristin and silydianin do not possess 1,4-dioxan ring system and thus, do not display significant antihepatotoxic activity. Based on the above hypothesis we learned that 1,4-dioxane ring system plays an important role in exhibiting antihepatotoxic activity, and hence we have prepared some new pyrazoline derivatives bearing 1,4-dioxane ring system and evaluated them for antihepatotoxic activity against CCl4induced hepatotoxicity in rats. Material and Methods: The titled pyrazolines were prepared by refluxing 2,3-dihydro-1,4-benzodioxane-6-yl)-1-substituted-phenylprop2-en-1-one derivatives with hydrazine hydrate in absolute ethanol and few drops of glacial acetic acid. The synthesized compounds were evaluated for antihepatotoxic activity by measuring different biochemical parameters glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP) and total protein against CCl4-induced hepatotoxicity in Wistar albino rats as well as histopathological study of the liver. Results: The administration of silymarin (standard drug) and synthesized compounds at a dose level of 10 mg/Kg body weight, prevented CCl4-induced elevation of SGOT, SGPT, ALP, and prevented decrease in total protein. The histopathological studies also showed significant recovery of hepatocytes of the liver in the standard drug and compound-treated animals. Conflict of Interest: None Study of Silymarin on Ethanol Induced Hepatotoxicity and Expression of Bcl-2, Bax and p53 Levels P Vasanth Raj, K Nitesh, P Jain, M Neena Sankhe, J Venkata Rao, C Mallikarjuna Rao, N Udupa Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka Background and Aims: Oxidative stress plays a pivotal role in the pathogenesis and progression of alcoholic liver disease (ALD). Considering the antihepatotoxic property of silymarin, a well known antioxidant (flavonoid); we investigated the hepatoprotective effect of silymarin and underlying mechanism(s). Methods: Twenty-four Wistar strain albino rats (180–200 g) of either sex were used. The animals were divided into three groups and treated for 60 days as follows: (1) normal control group received the vehicle (sodium CMC 0.3%); (2) ethanol group was administered ethanol 3.6 g/Kg (30%, 10 mL/Kg) 1 hour after ingestion of sodium CMC 0.3%; (3) ethanol plus silymarin group received silymarin 100 mg/Kg 1 hour prior to the administration of ethanol 3.6 g/Kg. Animals received ethanol and silymarin by oral route daily. Liver damage was evaluated by histopathology and liver function test. At molecular level, expression of P53, Bax and bcl-2 was determined by reverse transcriptase polymerase chain reaction (RT PCR). Results: Silymarin at 100 mg/Kg each ameliorated ethanol-induced macrovesicular steatosis and parenchymatous degeneration in hepatocytes, and decreased serum aminotransferases level. Ethanol downregulated antiapoptotic Bcl-2, upregulated pro apoptotic P53 and Bax mRNA levels in liver hepatocytes, thus, inducing apoptosis. However, this alteration in mRNA levels of P53, Bax and Bcl-2 was significantly prevented by silymarin treated animals at a dose of 100 mg/Kg body weight. Conclusion: Together, these results identify the biological efficacy of silymarin against ethanol-induced hepatotoxicity in rats. Hence, silymarin merits further investigation to support its molecular mechanism. Conflict of Interest: None Hepatoprotective Action of Dehydrozingerone in Carbon Tetrachloride and Thioacetamide-induced Hepatotoxicity in Wistar Rats N Kumar, P Vasanth Raj, A Tiwari, A Chaudhary, C Mallikarjuna Rao, N Gopalan Kutty, N Udupa Manipal College of Pharmaceutical Sciences, Manipal University, Manipal Background and Aims: Dehydrozingerone (DZ) is a prototype constituent of ginger and has shown radioprotection through its antioxidant activity. Chemically DZ is a chalcone in nature and can be prepared easily by reactions of vanillin with acetones. Antioxidant activity 03_JCEH-Abstract.indd 40 3/18/2011 11:13:05 AM