AIM: To assess the defensive nature of Sargassum polycystum (S. polycystum) (Brown alga) against acetaminophen (AAP)-induced changes in drug metabolizing mi crosomal enzyme system, tumor necrosis factor (TNF-α) and fine structural features of the liver during toxic hepatitis in rats. METHODS: Male albino Wistar strain rats used for the study were randomly categorized into 4 groups. GroupⅠconsisted of normal control rats fed with standard diet. GroupⅡrats were administered with acetaminophen (800 mg/kg body weight, intraperitoneally). GroupⅢrats were pre-treated with 5. polycystum extract alone. GroupⅣrats were orally pre-treated with S. polycystum extract (200 mg/kg body weight for 21 d) prior to acetaminophen induction (800 mg/kg body weight, intraperitoneally). Serum separated and liver was excised and microsomal fraction was isolated for assaying cytochrome P450, NADPH Cyt P450 reductase and bs. Serum TNF-αwas detected using ELISA. Fine structural features of liver were examined by transmission electron microscopy. RESULTS: Rats intoxicated with acetaminophen showed considerable impairment in the activities of drug metabolizing microsomal enzymes, such as cytochrome P450, NADPH Cyt P450 reductase and bs when compared with the control rats. The rats intoxicated with acetaminophen also significantly triggered serum TNF-αwhen compared with the control rats. These severe alterations in the drug metabolizing enzymes were appreciably prevented in the rats pretreated with 5. polycystum. The rats pretreated with S. polycystum showed considerable inhibition in the elevation of TNF-αcompared to the rats intoxicated with acetaminophen. The electron microscopic observation showed considerable loss of structural integrity of the endoplasmic reticulum, lipid infiltration and ballooning of mitochondria in the acetaminophen-intoxicated rats, whereas the rats treated with S. polycystum showed considerable protection against acetaminophen-induced alterations in structural integrity. CONCLUSION: These observations suggest that the animals treated with 5. polycystum extract may have the ability to protect the drug metabolizing enzyme system and mitochondrial functional status from free radical attack, thereby showing its defense mechanism in protecting hepatic cells from acetaminophen toxic metabolite N-acetyl-para-benzoquinone-imine (NAPQI). AIM: To assess the defensive nature of Sargassum polycystum (S. polycystum) (Brown alga) against acetaminophen (AAP)-induced changes in drug metabolizing mi crosomal enzyme system, tumor necrosis factor (TNF-α) and fine structural features of the liver METHODS: Male albino Wistar strain rats used for the study were randomly categorized into 4 groups. GroupIconsisted of normal control rats fed with standard diet. GroupIIrats were administered with acetaminophen (800 mg/kg body weight, intraperitoneally). GroupIIIrats were pre-treated with 5. polycystum extract alone. GroupIVrats were orally pre-treated with S. polycystum extract (200 mg/kg body weight for 21 days) prior to acetaminophen induction (800 mg/kg body weight, intraperitoneally). Serum Separated and liver was excised and microsomal fraction was isolated for assaying cytochrome P450, NADPH Cyt P450 reductase and bs. Serum TNF-αwas detected using ELISA. Fine structural features of liver were ex The rats intoxicated with acetaminophen: Rats intoxicated with acetaminophen showed considerably impairment in the activities of drug metabolizing microsomal enzymes, such as cytochrome P450, NADPH Cyt P450 reductase and bs when compared with the control rats. The rats intoxicated with acetaminophen also wereties triggered Serum TNF-αwhen compared with the control rats. These severe alterations in the drug metabolizing enzymes were appreciably prevented in the rats pretreated with 5. polycystum. The rats pretreated with S. polycystum showed significant inhibition in the elevation of TNF-αcompared to the rats Intoxicated with acetaminophen. The electron microscopic observation specimen concluded loss of structural integrity of the endoplasmic reticulum, lipid infiltration and ballooning of mitochondria in the acetaminophen-intoxicated rats, but the rats treated with S. polycystum with regard to protection against acetaminophen-induced alterations in structu Ral integrity. CONCLUSION: These observations suggest that the animals treated with 5. polycystum extract may have the ability to protect the drug metabolizing enzyme system and mitochondrial functional status from free radical attack, extends showing its defense mechanism in protecting hepatic cells from acetaminophen toxic metabolite N -acetyl-para-benzoquinone-imine (NAPQI).