Acetylhydrazine hepatotoxicity*1

Bahri, Aman

doi:10.1016/0041-008x(81)90343-4

Cited by 28 publications

(15 citation statements)

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“…Although treatment with RFP does not increase the hepatotoxicity of Ac-Hz in experimental animals (27,28), our study shows a high incidence of liver dysfunction with the IRS regimen. Therefore, we think that, at least in humans, RFP may accelerate the metabolism of INH, so that a large amount of Ac-Hz and later acylating agents are produced by the microsomal MFO.…”

Section: Discussionmentioning

confidence: 92%

Elevated Serum Aminotransferase Induced by Isoniazid in Relation to Isoniazid Acetylator Phenotype

1986

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Of 143 patients with pulmonary tuberculosis receiving isoniazid therapy, 52 (36%) had a transient elevation in serum aminotransferases. Among 74 patients taking isoniazid, rifampicin and streptomycin, 35 (47%) had such an increase, while of 69 patients taking isoniazid, amino-salicylic acid and streptomycin, 17 (24%) did; this difference was significant. Isoniazid therapy could be continued in all patients with the abnormal test results. In 36 of the patients receiving isoniazid, rifampicin and streptomycin, isoniazid and its metabolites were studied in the serum and urine using high-performance liquid chromatography after the oral administration of 10 mg per kg of isoniazid. We had chosen for this test 18 patients with normal aminotransferase levels and 18 with abnormal levels. There were 14 rapid acetylators in the patients with abnormal aminotransferase levels and 7 rapid acetylators in the patients with normal levels; this difference was significant. These results indicate that liver dysfunction is more often caused by an isoniazid/rifampicin regimen, and patients who are rapid acetylators are more susceptible.

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Section: Discussionmentioning

confidence: 92%

Elevated Serum Aminotransferase Induced by Isoniazid in Relation to Isoniazid Acetylator Phenotype

1986

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“…This metabolite, acetylhydrazine (Figure 1) is a potent hepatotoxin in experimental animals (Mitchell et al, 1976;Bahri et al,1981). The hepatotoxicity is dependent on further metabolism of acetylhydrazine by the microsomal enzymes postulated to yield a reactive acylating agent Bahri et al, 1981) (Figure 1). …”

Section: Introductionmentioning

confidence: 99%

A Study of the Effects of Rifampicin on Isoniazid Metabolism in Human Volunteer Subjects

1985

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1 The effect of rifampicin on the metabolism of isoniazid in human volunteer subjects has been investigated. 2 The urinary metabolites of isoniazid after a single dose and after six daily doses of isoniazid plus rifampicin were examined. 3 The isoniazid-rifampicin combination clearly increased the ratio of urinary 6-β-hydroxycortisol to 17-hydroxycorticosteroids, indicating that induction of the microsomal enzymes had occurred. 4 However, no significant changes in the urinary metabolites of isoniazid were detected, and therefore it is not possible to predict the effect of rifampicin on isoniazid hepatotoxicity.

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“…INH and RIF solutions were prepared separately in sterile distilled water. The pH of RIF solution was adjusted to 3.0 with 0.1 mol/L HCl [9] . INH and RIF were administered orally for 28 d. Liver transaminases and bilirubin were estimated on d 0, 14, 21, and 28 in both control (saline treated) and experimental animals.…”

Section: Methodsmentioning

confidence: 99%

Effect of garlic on isoniazid and rifampicin-induced hepatic injury in rats

Pal¹

2006

WJG

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AIM: To evaluate the hepatoprotective effect of garlic on liver injury induced by isoniazid (INH) and rifampicin (RIF). METHODS:Wistar rats weighing 150-200 g were treated orally with 50 mg/kg of INH and RIF daily each for 28 d. For hepatoprotective studies, 0.25 g/kg per day of freshly prepared garlic homogenate was administered orally half an hour before the INH+RIF doses. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin were estimated on d 0, 14, 21, and 28 in all the rats. Histological analysis was carried out to assess the injury to the liver. Lipid peroxidation (LPO) as a marker of oxidative stress and non-protein thiols (glutathione) for antioxidant levels were measured in liver homogenate. RESULTS:The treatment of rats with INH+RIF (50 mg/kg per day each) induced hepatotoxicity in all the treated animals as judged by elevated serum ALT, AST, and bilirubin levels, presence of focal hepatocytic necrosis (6/8) and portal triaditis (8/8). Garlic simultaneously administered at a dose of 0.25 g/kg per day prevented the induction of histopathological injuries in INH+RIF co-treated animals, except in 4 animals, which showed only moderate portal triaditis. The histological changes correlated with oxidative stress in INH+RIF treated animals. The group which received 0.25 g/kg per day garlic homogenate along with INH+RIF showed higher levels of glutathione (P < 0.05) and low levels of LPO (P < 0.05) as compared to INH+RIF treated group.

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Acetylhydrazine hepatotoxicity*1

Cited by 28 publications

References 0 publications

Elevated Serum Aminotransferase Induced by Isoniazid in Relation to Isoniazid Acetylator Phenotype

Elevated Serum Aminotransferase Induced by Isoniazid in Relation to Isoniazid Acetylator Phenotype

A Study of the Effects of Rifampicin on Isoniazid Metabolism in Human Volunteer Subjects

Effect of garlic on isoniazid and rifampicin-induced hepatic injury in rats

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