Isoniazid and rifampicin treatment on phospholipids and their subfractions in liver tissue of rabbits.
Although combined treatment of isoniazid (INH) and rifampicin (RIF) has been documented to induce hepatotoxicity and hepatocellular damage, their effect on liver tissue phospholipids is still unknown. Because phospholipids constitute an integral part of hepatocellular membrane, studies were conducted to evaluate the effect of individual and combined treatment of INH and RIF on liver tissue phospholipids in rabbits. Simultaneous administration (i.p.) of INH and RIF (group IV; n = 6), each at a dose of 25 mg/kg for 11 days, caused a significant elevation of phospholipids in plasma from day 5 till day 11. This treatment also caused a significant fall in total inorganic phosphorous, phosphatidylcholine (PC), and cardiolipin (CL) with concomitant increase in phosphatidylethanolamine (PE) and phosphatitylserine (PS) subfractions of phospholipids in the liver tissue of rabbits. Though INH-alone treatment (group II; n = 5) produced a significant fall in total inorganic phosphorous content in the liver tissue, the phospholipid subfractions remain unaltered. RIF-alone treatment (group III; n = 5) did not produce any alteration in phospholipids and their subfractions in liver tissue and plasma of rabbits, and they were comparable to saline-treated control (group I; n = 5). It is likely that simultaneous treatment of INH and RIF could cause choline deficiency, resulting in lowering of phospholipids in the hepatocellular membrane and obstruction of lipoprotein synthesis, culminating in liver injury.
Karthikeyan
S
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Department of Pharmacology and Environmental Toxicology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, India. sivanesankarthikeyan@rediffmail.com
D000818:Animals; D000904:Antibiotics, Antitubercular / Q000633:toxicity*; D000995:Antitubercular Agents / Q000633:toxicity*; D002855:Chromatography, Thin Layer; D004347:Drug Interactions; D007538:Isoniazid / Q000633:toxicity*; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D010710:Phosphates / Q000378:metabolism; D010743:Phospholipids / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D011817:Rabbits; D012293:Rifampin / Q000633:toxicity*
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D010710:Phosphates; D010743:Phospholipids; D007538:Isoniazid; D012293:Rifampin