Phospholipid and cholesterol alterations accompany structural disarray in myelin membrane of rats with hepatic encephalopathy induced by thioacetamide

Fulminant hepatic failure is often associated with a wide range of neurological symptoms which are collectively referred to as hepatic encephalopathy. Fulminant hepatic failure with associated hepatic encephalopathy has a poor prognosis with the currently available sure treatment being only liver transplantation. This is largely owing to the lack of understanding of critical factors involved in the etiology of the condition. Lipid changes have been implicated in cerebral derangements characteristic of hepatic encephalopathy. About 79% of the brain lipid is concentrated in the myelin fraction where they play an important role in ion balance and conduction of nerve impulses. Hence, in the present study we aimed to investigate changes in myelin lipid composition and structure. Myelin was isolated by sucrose density gradient centrifugation from cerebral cortex of male Wistar rats (250-300 g body weight) treated with 300 mg/kg body weight thioacetamide administered twice at 24h interval to induce hepatic encephalopathy. Significant decrease was observed in the cholesterol and phospholipids content of myelin from treated rats. Sphingomyelin, phosphatidylserine and phosphatidylethanolamine content also decreased significantly following 18 h of thioacetamide administration. However, phosphatidylcholine levels remained unaltered. Transmission electron microscopic observation of myelin membrane from cerebral cortex sections showed considerable disorganization in myelin structure. Increase in malondialdehyde levels precede lipid changes leading to the speculation that oxidative damage may be the critical factor leading to decrease in the anionic phospholipids. Changes in myelin were evident only in later stages of hepatic encephalopathy indicating that myelin alteration may not play a role in early stages of hepatic encephalopathy. Nevertheless, myelin alteration may have a crucial role to play in various psycho-motor alterations during later stages of hepatic encephalopathy.