Role of hydrazine in the mechanism of isoniazid hepatotoxicity in rabbits

Sarich, Troy C.; Youssefi, Mohammed; Zhou, Ting; Adams, Stephen P.; Wall, Richard A.; Wright, James M

doi:10.1007/s002040050347

Cited by 94 publications

(61 citation statements)

References 23 publications

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“…In present study in toxic control group increased level of TBARS (a marker for oxidative stress), reduction in the GSH concentration During the metabolism of INH, hydrazine is produced directly (from INH) or indirectly (from acetyl hydrazine). From earlier study (Garner et al, 2004) it is evident that hydrazine play a role in INHinduced liver damage in rats, which is consistent with the report by Sarich et al, 1996. The combination of INH and RIF was reported to result in higher rate of inhibition of biliary secretion and an increase in liver cell lipid peroxidation, and cytochrome P450 was thought to be involved the synergistic effect of RIF on INH (Ramaiah et al, 2001).…”

Section: Percent Survivalsupporting

confidence: 67%

Protective role of Ficus benghalensis against isoniazid-rifampicin induced oxidative liver injury in rat

Parameswari¹,

Saleem²,

Chandrasekar³

et al. 2012

Rev. bras. farmacogn.

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The present study was made to investigate the protective effect of methanolic extract of Ficus benghalensis L., Moraceae, on isoniazid-rifampicininduced hepatotoxicity in rats. Rats were divided into six different groups; group 1 served as a control, group 2 received isoniazid and rifampicin (100 mg/ kg, i.p.), in sterile water, groups 3, 4 and 5 received 100, 200 & 300 mg/kg bw, p.o. methanolic extract of F. benghalensis and group 6 received Liv 52. All the treatment protocols followed 21 days and after rats were sacrificed blood and liver were used for biochemical and histological studies, respectively. Administration of isoniazid and rifampicin caused a significant elevation in the levels of liver marker enzymes (p<0.05 and p<0.01) and thiobarbituric acid reactive substances (p<0.001) in experimental rats. Administration of methanolic extracts of F. benghalensis significantly prevented isoniazid-rifampicin-induced elevation in the levels of serum diagnostic liver marker enzymes and TBARS level in experimental groups of rats. Morever, total protein and reduced glutathione levels were significantly (p<0.001) increased in treatment group. The effect of extract was compared with a standard drug, Liv 52. The changes in biochemical parameters were supported by histological profile. It is to be concluded that the methanolic extract of F. benghalensis protects against isoniazid and rifampicin-induced oxidative liver injury in rats.

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Section: Percent Survivalsupporting

confidence: 67%

Protective role of Ficus benghalensis against isoniazid-rifampicin induced oxidative liver injury in rat

Parameswari¹,

Saleem²,

Chandrasekar³

et al. 2012

Rev. bras. farmacogn.

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“…It is unlikely that the rat model represents the same mechanism of INH-induced hepatotoxicity that occurs in humans because the characteristics are very different. Hydrazine has also been implicated as a potential hepatotoxic metabolite of INH (Blair et al, 1985;Gent et al, 1992;Noda et al, 1983;Sarich et al, 1996); however, given its potent hepatotoxic effects it is more likely that hydrazine would cause acute liver injury rather than liver injury with a delayed onset.…”

Section: Introductionmentioning

confidence: 99%

Isoniazid-induced liver injury and immune response in mice

Metushi¹,

Uetrecht

2013

Journal of Immunotoxicology

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Isoniazid (INH) is associated with one of the highest incidences of idiosyncratic drug-induced liver failure of any commonly prescribed drug. The mechanism of this liver injury remains uncertain, and a valid animal model would greatly facilitate mechanistic studies. Most studies of INH-induced liver toxicity have been acute studies performed in rats with high doses of the drug, and this is very different from the idiosyncratic liver injury that occurs in humans. It has previously been demonstrated that covalent binding of INH in the liver of mice is greater than in rats and more like that in humans. Therefore, mice should be a better species in which to develop an animal model of INH-induced liver injury. Treatment of Cbl-b À/À and PD1 À/À mice, which have impaired immune tolerance, resulted in greater injury than their C57BL/6 background, but not liver failure. This suggested that the injury was mediated by the adaptive immune system; however, Rag À/À mice, which do not have competent T-and B-cells, sustained more liver injury than C57BL/6 wild-type mice. This suggested that the adaptive immune system also played a protective role. INH treatment also led to a decrease in the inflammatory cytokines IL-1a and IL-12, which suggests that the drug may have immunosuppressive properties. In short, a mouse model was developed of INH-induced liver injury in which the immune system appears to play a both protective and pathogenic role, but this study was unable to develop a model of INH-induced liver failure.

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“…Hydrazine, a toxic intermediate product of INH metabolism can be produced both directly (from INH) and indirectly (from acetylhydrazine). The severity of INHinduced hepatocellular damage has a positive correlation with the plasma hydrazine concentrations (Sarich et al 1996). Both hydrolysis reactions involve an amidase enzyme.…”

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confidence: 99%

Quantitative rat liver function test by galactose single point method

et al. 2008

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SummaryThe purpose of this study was to investigate the galactose single point (GSP) method, a residual liver function test recently recommended by the US Food and Drug Administration, which can be a useful tool for rat liver function measurement. Rats were treated either with carbon tetrachloride (CCl 4 ) alone (1 mL/kg, intraperitoneally [i.p.]) for one day or with isoniazid (INH) alone (150 mg/kg, i.p.) or (in order to ameliorate the effects of INH) with a combination of INH and bis-p-nitrophenyl phosphate (BNPP) (25 mg/kg, i.p.) for 21 days. Hepatotoxicity was assayed by plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and scores of histological activity index-necroinflammation (HAI-NI) of the respective liver specimens. The GSP method in rats was defined by the galactose blood level after 60 min. Significant differences in GSP values were observed between controls and the CCl 4 -treated rats. After 21 days of treatment, no significant changes in AST and ALT values were observed among the control, INH and INH-BNPP groups. There were significant differences in average GSP values for controls (P , 0.001) and INH-BNPP (P , 0.001) compared with INH alone. Highly significant correlations (P , 0.001) were obtained between GSP and scores of HAI-NI for all the groups. GSP was concluded to be a more sensitive biomarker of INH-induced hepatotoxicity than AST or ALT in the rats. The GSP method has been proved to be a simple and useful tool for the quantitative determination of liver function in rats, which can possibly be extended to other animals.

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Role of hydrazine in the mechanism of isoniazid hepatotoxicity in rabbits

Cited by 94 publications

References 23 publications

Protective role of Ficus benghalensis against isoniazid-rifampicin induced oxidative liver injury in rat

Protective role of Ficus benghalensis against isoniazid-rifampicin induced oxidative liver injury in rat

Isoniazid-induced liver injury and immune response in mice

Quantitative rat liver function test by galactose single point method

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