Hepato- and neuro-protective influences of biopropolis on thioacetamide-induced acute hepatic encephalopathy in rats

Abstract

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome ultimately occurs as a complication of acute or chronic liver failure; accompanied by hyperammonemia. This study aimed to evaluate the potential of biopropolis as a hepato and neuroprotective agent using thioacetamide (TAA)-induced acute HE in rats as a model. Sixty Wistar rats were divided into five groups: Group 1 (normal control) received only saline and paraffin oil.Group 2 (hepatotoxic control) received TAA (300 mg/kg, once). Groups 3, 4 and 5 received TAA followed by vitamin E (100 mg/kg) and biopropolis (100 and 200 mg/kg), respectively, daily for 30 days. Evidences of hepatic encephalopathy were clearly detected in TAA-hepatotoxic group including significant elevation in the serum level of ammonia, liver functions, increased oxidative stress in liver and brain, apoptotic DNA fragmentation and overexpression of iNOS gene in brain tissue. The findings for groups administered biopropolis, highlighted its efficacy as a hepato and neuro-protectant through improving the liver functions, oxidative status and DNA fragmentation as well as suppressing the brain expression of iNOS gene. In conclusion, bioproplois, at a dose of 200 mg/kg/day protected against TAA-induced HE through its antioxidant and antiapoptotic influence; therefore, it can be used as a protective natural product.Keywords: Biopropolis; hepatic encephalopathy; thioacetamide; iNOS; vitamin E. IntroductionHepatic encephalopathy (HE) is a neuropsychiatric syndrome resulting from acute or chronic liver failure (Lizardi-Cervera et al. 2003). HE affects a huge number of patients worldwide leading to a mortality rate of 50 to 90% (Raghavan and Marik 2006). HE causes a wide range of clinical manifestations, including psychomotor dysfunctions, sensory abnormalities, poor concentration, increased reaction time and impaired memory. Patients commonly develop stupor, coma and death in severe cases.The mechanism of HE has not been fully explained. However, hyper-ammonemia has been suggested to play the main role in HE pathogenesis and to be responsible for the direct and indirect alterations in cerebral metabolism and hence encephalopathy (Frederick 2011;Mustafa et al. 2013).Thioacetamide (TAA) is used to induce an experimental rat model mimicking acute hepatic failure and HE. This model has been validated to be a satisfactory model of HE (Avraham et al. 2006). TAA undergoes extensive metabolism to highly reactive metabolites that binds to liver macromolecules resulting in hepatic necrosis, hyperammonemia (Swapna et al. 2006) and extensive oxidative stress (Sathyasaikumar et al. 2007). Studies demonstrated that centrilobular necrosis is apparent after single dose of TAA, while cirrhosis, liver cell adenomas and liver cancer usually develop after chronic administration (Waters et al. 2005).Oxidative stress has long been involved in the pathogenesis of acute and chronic liver damage in many conditions such as toxin exposures, bile duct obstruction, excess alcoholism, liver ischemia, and viral inf...

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