{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T23:27:55Z","timestamp":1781220475681,"version":"3.54.1"},"reference-count":21,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2007,6,15]],"date-time":"2007-06-15T00:00:00Z","timestamp":1181865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:p><jats:bold>Aim:\u2002<\/jats:bold>Biochemical characterization of long\u2010term toxic manifestations of anti\u2010tubercular (anti\u2010TB) drugs \u2013 rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) \u2013 individually and in two combinations: (i) RIF\u2003+\u2003INH, and (ii) RIF\u2003+\u2003INH\u2003+\u2003PZA in Wistar rats.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold>Animals received anti\u2010TB drugs \u2013 alone or in combination \u2013 once daily p.o. for up to 90 days (doses, in mg\/kg: RIF, 250; INH, 50; PZA, 100). Assays for alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin (serum) and lipid peroxidation (LPO), glutathione (GSH), glutathione peroxidase (GPx), catalase, Na+K+\u2010ATPase and CYP 2E1 (liver) were performed to assess liver toxicity. Clinical biochemistry was done by commercial kits. Determinations were made at 0, 15, 30 and 90 days of treatment schedule.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold>Anti\u2010TB drugs\u2010treated animals showed abnormal rises or falls (&gt;1.5\u20132 fold) in the serum\/liver parameters. Mild hyperlipidemia, hypercholesterolemia and hyperuricemia were the other pathologies. Of all the treated groups, INHalone or in combination with other drugs produced a progressive enhancement of toxicity over 15\u201390 days. The<jats:italic>in vivo<\/jats:italic>results were further supported by<jats:italic>in vitro<\/jats:italic>results (MTT assay, GSH and LPO) in primary cultures of rat hepatocyte. Results indicated that anti\u2010TB drugs in combination: (i) caused membrane damage resulting in leakage of ALT, ALP and bilirubin; (ii) caused imbalance in endogenous enzymatic oxidant\u2013antioxidant defense via increased lipid peroxidation and in glutathione homeostasis; and (iii) enhanced the CYP 2E1\u2010mediated bioactivation mechanism.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold>Toxicity manifestations seemed to be heptocytic injury targeted at hepatocytes, bile ducts or sinusoidal cells related to hepatitis and primary biliary cholestasis.<\/jats:p>","DOI":"10.1111\/j.1872-034x.2007.00129.x","type":"journal-article","created":{"date-parts":[[2007,6,16]],"date-time":"2007-06-16T13:54:59Z","timestamp":1182002099000},"page":"845-853","source":"Crossref","is-referenced-by-count":44,"title":["Potentiation of isoniazid\u2010induced liver toxicity by rifampicin in a combinational therapy of antitubercular drugs (rifampicin, isoniazid and pyrazinamide) in Wistar rats: A toxicity profile study"],"prefix":"10.1111","volume":"37","author":[{"given":"Sheikh Abdullah","family":"Tasduq","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peerzada","family":"Kaiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhash Chander","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh Kamal","family":"Johri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,6,15]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2005.11.001"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510310129"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200209-998OC"},{"key":"e_1_2_6_5_2","first-page":"148","article-title":"Isoniazid associated hepatitis","volume":"1","author":"Alexender MR","year":"1982","journal-title":"Clin Pharmacol"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hepres.2005.01.005"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.1631"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2006.01.027"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1191\/0960327106ht601oa"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2005.07.014"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1191\/0960327103ht406oa"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/inpract.14.4.193"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.4.2234"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.06.017"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.30.040190.003131"},{"key":"e_1_2_6_16_2","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/S0022-3565(24)38190-X","article-title":"Inhibition of Isoniazid\u2010Induced Hepatotoxicity in Rabbits by Pretreatment with an Amidase Inhibitor","volume":"289","author":"Sarich TC","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_17_2","first-page":"284","article-title":"Isoniazid \u2013 rifampicin fulminant hepatitis. 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