Defensive nature of Sargassum polycystum (Brown alga) against acetaminophen-induced toxic hepatitis in rats: role of drug metabolizing microsomal enzyme system, tumor necrosis factor-alpha and fate of liver cell structural integrity.
OBJECTIVE
To assess the defensive nature of Sargassum polycystum (S. polycystum) (Brown alga) against acetaminophen (AAP)-induced changes in drug metabolizing microsomal enzyme system, tumor necrosis factor (TNF-alpha) 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. Group I consisted of normal control rats fed with standard diet. Group II rats were administered with acetaminophen (800 mg/kg body weight, intraperitoneally). Group III rats were pre-treated with S. polycystum extract alone. Group IV rats 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 b(5). Serum TNF-alpha was 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 b(5) when compared with the control rats. The rats intoxicated with acetaminophen also significantly triggered serum TNF-alpha when compared with the control rats. These severe alterations in the drug metabolizing enzymes were appreciably prevented in the rats pretreated with S. polycystum. The rats pretreated with S. polycystum showed considerable inhibition in the elevation of TNF-alpha compared 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.


CONCLUSIONS
These observations suggest that the animals treated with S. 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).
Raghavendran
H Balaji
HB
Department of Biochemistry, University of Madras, Guindy campus, Chennai, India. hbr_bala@yahoo.com
Sathivel
A
A
Devaki
T
T
D000082:Acetaminophen / Q000009:adverse effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016227:Benzoquinones; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D042966:Cytochrome-B(5) Reductase / Q000032:analysis; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D007097:Imines; D008658:Inactivation, Metabolic / Q000502:physiology; D008099:Liver / Q000737:chemistry / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008854:Microscopy, Electron; D008862:Microsomes, Liver / Q000201:enzymology* / Q000502:physiology; D008928:Mitochondria / Q000648:ultrastructure; D009249:NADP / Q000032:analysis; D009251:NADPH-Ferrihemoprotein Reductase / Q000032:analysis; D010936:Plant Extracts / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D044647:Sargassum / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D007097:Imines; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D000082:Acetaminophen; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D042966:Cytochrome-B(5) Reductase; D009251:NADPH-Ferrihemoprotein Reductase; C028473:N-acetyl-4-benzoquinoneimine