Lactulose and donepezil ameliorate thioacetamide-induced hepatic encephalopathy in rats

ABSTRACT

Hepatic encephalopathy [HE] is neuropsychological complication that is common in patients with acute or chronic liver disease as well as in porto-systemic shunting of blood flow. The pathophysiology of this disease is quite complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Thioacetamide [TAA]-induced HE is a reliable model of HE in which rats were given thioacetamide [TAA] 200mg/kg orally for 2 consecutive days. The TAA group showed lower motor activity than the normal group by using open field and forced swimming tests. Oxidative stress conditions were manifested by free radical production, lipid peroxidation, reduced glutathione and nitric oxide contents. Alterations in the metabolism of monoamine neurotransmitters have been proposed to be involved in the development of the HE associated with experimental and human liver failure. Pretreatment with lactulose or donepezil could counteract these effects. The protective effect of both lactulose and donepezil can be attributed to their antioxidant and neuromodulatory potential