Case report acute and fatal isoniazidinduced hepatotoxicity. The above results prove the fact that cocrystallization qct with inh almost eliminates isoniazid induced hepatotoxicity, which. Hepatotoxicity associated with isoniazid preventive therapy. Inhibition of isoniazidinduced hepatotoxicity in rabbits. The aim of this study is to establish the ethnomedicinal claim of hepatoprotective effects of fruit pulp extract of telfairia occidentalis against rifampicin rif and isoniazid inh induced oxidative stress in rats. Concurrentadministration of pyridoxinemay prevent neuropathy. A 72yearold caucasian male, who was started on isoniazid after the. Management of common side effects of inh isoniazid, rif rifampin, pza pyrazinamide, and emb ethambutol 1.
A higher level of free inh might be the cause of the high incidence of liver. Inhibition of isoniazid induced hepatotoxicity in rabbits by pretreatment with an amidase inhibitor. Cytochrome p450 2e1 cyp2e1 is thought to contribute to the synergistic effects of rif and inh. Shen, c isoniazid induced hepatotoxicity in rat hepatocytes of gel entrapment culture, toxicology letters, 20061101 crossref en.
Metabolic processes leading to isoniazid induced hepatotoxicity figure 2. The negative findings from controlled clinical trial might have been caused by insufficient statistical power or. Gabapentin, a gammaaminobutyric acid gaba analogue, has infrequently been reported to cause liver injury. Drug induced liver injury is a cause of acute and chronic liver disease the liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Nov 15, 2001 given the high prevalence of hepatitis c virus infection among idus, the association between hcv infection and elevated hepatic transaminase values, and the potential for isoniazid to cause hepatotoxicity, the risk of hepatotoxicity among idus receiving isoniazid for treatment of latent m. Hot aqueous leaf extract of lasianthera africana icacinaceae. Various studies have shown that a dosage of 50 mgkg b. Isoniazid inh is highly effective for the management of tuberculosis. Sample of liver tissue, with arrows pointing to necrotic areas. Oct 27, 2012 the first pattern is characterised by an increase in serum transaminase activity that occurs soon usually within the first 15 days after initiation of treatment. Pdf protective effect of methanolic extract of annona. She was admitted to the hospital for epigastric and right sided flank pain of oneweek duration. Saroufim 2 department of pharmacy practice, school of pharmacy, lebanese american university lau, p.
Evaluation of quantitative phytochemicals, liver enzymes and. While in the cocrystal group, the elevation levels of asa and ala activity are effectively attenuated, and reaches to that of untreated controls. A 65yearold female diagnosed with latent mycobacterium tuberculosis infection was receiving oral isoniazid 300 mg daily. Mild inh hepatotoxicity refers to hepatic injury that is typically subclinical and evidenced only by mildly elevated serum aminotransferases usually isoniazid. Hepatoprotective properties of sugarcane juice and vitamin c. Protective effects of kaempferol on isoniazid and rifampicininduced hepatotoxicity springerlink. Pdf acute and fatal isoniazidinduced hepatotoxicity. Isoniazid 50 mgkg was administered to all the animals for 28 days orally. Protective effects of metallothionein on isoniazid and rifampicin. Hepatotoxicity of antituberculosis therapy american thoracic society. Isoniazid is a widely used drug for the treatment of tuberculosis all over the world.
The aim of the study was to evaluate the phytochemicals and ameliorative effects of aqueous extracts of brysocarpus coccineus on serum liver enzymes in isoniazid. Protective effects of metallothionein on isoniazid and. In a prospective study we genotyped 89 patients treated with isoniazid inh for latent tuberculosis. The incidences of hepatotoxicity are ranged as the following. Cyp2e1 genotype and isoniazid induced hepatotoxicity in patients treated for latent tuberculosis. Hepatotoxicity from hepatic toxicity implies chemicaldriven liver damage.
It can result in elevated serum liver enzymes and hepatic failure. Previous mechanistic hypotheses have classified this type of drug. Selected pharmaceutical excipient prevent isoniazid and. A model of isoniazid induced hepatotoxicity in rabbits. Isoniazid isonicotinylhydrazine, inh is the most active drug for the treatment of tuberculosis caused by susceptible strains. Inh has been widely used for the treatment of both active and latent forms of mycobacterium tuberculosis infections. To compare the hepatoprotective properties of sugarcane saccharum officinarum. The inh metabolites, acetylhydrazine and hydrazine, have each been implicated as the causative hepatotoxin in inh induced hepatotoxicity. Pdf isoniazid inh is highly effective for the management of tuberculosis. Isoniazid inh, a widely used drug in the prophylaxis and treatment of tuberculosis, is associated with a 1 to 2% risk of severe and potentially fatal hepatotoxicity. Isoniazid metabolism and hepatotoxicity sciencedirect. Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity. Methods we selected english articles of studies in human from pubmed with the keywords pharmacogenetic and isoniazid and hepatotoxicity. Adherence to ninemonth isoniazid for latent tuberculosis.
Inh has since been associated with two syndromes of hepatotoxicity. Isoniazid preventive therapy, hepatitis c virus infection. Using criteria established by a panel of experts in hepatic disease, the public health service study showed that the incidence of. The role of oxygen free radicals in isoniazidinduced hepatotoxicity article pdf available in methods and findings in experimental and clinical pharmacology 208. Standard antituberculosis treatment and hepatotoxicity. Isoniazid isoniazid hepatotoxicity is a common complication of antituberculosis therapy that ranges in severity from.
In male wister rats, evidence of liver injury appears on treatment with isoniazid at a dose of 100 mgkg for 21 days and a metabolite of isoniazid, hydrazine plays an important role in liver injury. Context isoniazid preventive therapy for latent tuberculosis tb infection has been debated because of the risk of hepatotoxicity. L juice and vitamin c in mice on hepatotoxicity induced by inh isoniazid. Sage leaves salvia miltiorrhiza extract attenuates hepatic injury in isoniazid induced hepatotoxicity in rats 1eilyad issabeagloo, jafar asadi2mohammad taghizadieh, 3 1 department of pharmacology, medical sciences faculty, tabriz branch, islamic azad university, tabriz, iran. Although druginduced liver injury dili caused by different drugs is somewhat different, the clinical characteristics of inhinduced liver injury. Against isoniazid and rifampicin induced hepatotoxicity surinderkumar yogeeta, hanumanth rao balaji ragavender, and thiruvengadam devaki department of biochemistry, university of madras, guindy campus, chennai, india abstract the current study investigated the effect of 70% acetone extract of punica granatum l.
Mag was orally pretreated at the doses of 45 or 90mgkg 3h before rif and inh. Inh induced hepatitis inh h or elevated liver enzymes including hepatitis inh ele was diagnosed based on the clinical diagnostic scale cds designed for routine clinical practice. It is known to cause hepatotoxicity, but in rare instances, it can lead to prca. Detection of antiisoniazid and anticytochrome p450. Black and hispanic women are at higher risk for isoniazid induced hepatotoxicity. Alcoholic extract, aqueous extract and liv52 prevented the isoniazid induced hepatotoxicity. Abstract isoniazid inh is highly effective for the management of tuberculosis. Tuberculosis remains a health problem in developed countries like the united states. Inh also induces the p450 system and thus, acts as a source of free radicals 11. Inh metabolism has been thought to be associated with inh induced liver injury. This is consistent with covalent binding of the parent drug to liver. Inh metabolism has been thought to be associated with inhinduced liver injury. Objective to determine the rate of isoniazid hepatotoxicity in patients managed according to current guidelines and practice standards. Isoniazid is considered to be a highly effective drug in the prophylaxis and treatment of tuberculosis.
Hepatotoxicity of antitubercular treatments springerlink. This corroborated the high incidence of pyrazinamide induced hepatotoxicity which implied toxicity of pyrazinamide added to isoniazid and rifampicin relative to that of isoniazid induced hepatotoxicity found by a cohort study 15. Cyp2e1 genotype and isoniazidinduced hepatotoxicity in patients treated for latent tuberculosis. Inh metabolism has been thought to be associated with inh induced. Mice with inh rif induced hepatotoxicity showed significantly abnormal serum levels of ast and alt, and gsp value, and these values could be decreased by the administration of kaempferol p isoniazid inh continues to be a highly effective drug in the chemoprophylaxis and treatment of tuberculosis. Ameliorative effect of leucas cephalotes extract on isoniazid.
Antitubercular drugs have been known to be potentially hepatotoxic and may lead to drug induced liver injury. When it happens, isoniazid induced liver toxicity has been shown to occur in 50% of patients within the first 2 months of therapy. Protective effects of metallothionein on isoniazid and rifampicin induced hepatotoxicity in mice yong lian1,2. This article focuses on the acute and chronic isoniazid isonicotinic acid hydrazide inh toxicity. Liver injury was induced by cotreatment with rif 60mgkg and inh 60mgkg by gavage administration. The incidence of isoniazid inh and rifampicin rif induced abnormal liver enzyme activity is 27% but only 19% with inh alone. Feb 25, 2016 reactive metabolites proposed to be responsible for inh. Isoniazid inh remains a mainstay for the treatment of tuberculosis despite the fact that it can cause liver failure. A recent study did identify anti inh antibodies and antip450 autoantibodies in patients diagnosed with inh induced liver failure 22. Aluminumcontaining antacids may decrease absorption. Cyp2e1mediated inh metabolism may result from oxidative stress through the production of toxic metabolites or free radicals and lead to drug induced hepatotoxicity 15,16.
Ecd was administered orally for 21 days 150 and 300mgkg body weight. Isoniazid induced hepatotoxicity is a major concern in patients taking anti tuberculosis treatment and prophylaxis. The induction of deleterious hepatic changes has been seen while studying rats as a model for inh and rif induced hepatotoxicity previously. Isoniazidrelated hepatotoxicity annals of internal. Pdf this paper describes a case of an acute and fatal. Cureus isoniazid induced pure red blood cell aplasia. From 29th day onwards isoniazid was stopped and therapeutic agents normal. A clinical pharmacologists view of drug hepatotoxicity. Cyp2e1 genotype and isoniazidinduced hepatotoxicity in.
However, it can cause liver injury and even liver failure. Alphaglucosidase inhibitors and hepatotoxicity in type 2 diabetes. Since 1952, inh has been used as a frontline antimicrobial for tuberculosis tb. It may also be used for atypical types of mycobacteria, such as m. Three metabolites have been proposed to be responsible for inh. Since its introduction in 1952, several cases of inhinduced hepatotoxicity were reported 2.
This form of liver injury is not believed to be immune. Acute inh toxicity leads to central nervous system cns toxicity, including seizures, whereas chronic inh toxicity results in hepatotoxicity. There is ample evidence that elevation of hepatic cyp2e1 plays an essential role in the inhhepatotoxicity through generation of free radicals. Except for ethambutol, all the other firstline antitubercular drugs have the potential to result in hepatotoxicity and, after acetaminophen, isoniazid remains the second most common cause of drug induced acute liver failure in the united states. Isoniazid, also known as isonicotinylhydrazide inh, is an antibiotic used for the treatment of tuberculosis. However, administration of inh induces severe hepatic toxicity in some. Human pxr modulates hepatotoxicity associated with rifampicin. Inh metabolism is thought to be associated with inhinduced liver injury, 14, 15. Among the 4 standard antitb drugs, isoniazid inh is the most likely to cause drug induced liver toxicity. In this study, a nontargeted metabolic profiling method based on ultraperformance liquid chromatographyhigh resolution mass spectrometry uplchrms was used to characterize the plasma metabolic profile associated with the protective effects of the sagittaria sagittifolia polysaccharide ssp on isoniazid inh and rifampicin rfp induced hepatotoxicity in mice. Pharmacogenetic association between nat2 gene polymorphisms and isoniazid induced hepatotoxicity. In this study, we aimed to investigate the protective effects of ursodeoxycholic acid udca on liver injury caused by coadministration with isoniazid and rifampicin, two famous antitubercular drugs. For active tuberculosis it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol.
Druginduced liver injury dili is a problem of increasing signifi cance, but has. There is evidence that the inh metabolite hydrazine plays an important role in the mechanism of this toxicity. Management of common sign effects of inh final draft. Pure red blood cell aplasia prca is one of the uncommon causes of anemia. Mar 10, 20 rifampicin and isoniazid are often used together as a cotherapy to treat tuberculosis, but their combined use often leads to hepatoxicity in humans. Silymarin 50 mgkg was used as standard drug for this study. An infrequent but preventable cause of liver failure in children treated for latent tuberculosis infection. Pdf isoniazid metabolism and hepatotoxicity researchgate.
More than 900 drugs, toxins, and herbs have been reported to cause liver injury, and drugs account for 20 to 40% of all instances of fulminant hepatic failure. Even though inhinduced liver injury has been known and. Protective effects of kaempferol on isoniazid and rifampicin. Sil and vitamin c exhibited similarities in their capability to mitigate the toxic responses of isoniazid, which suggests that the adverse effects of isoniazid on the. Metabolism of inh leads to the production of hydrazine via both direct and indirect pathways. Hepatotoxicity of antitubercular drugs sciencedirect.
Autooxidation of inh involving free radicals has also been reported 17. Drug induced hepatotoxicity is a frequent cause of liver injury. Male wistar rats were randomly divided into four groups of 15 rats. Routine monitoring for hepatotoxicity in patients receiving isoniazid is. Monoammonium glycyrrhizinate protects rifampicin and. The present study was made to investigate the protective effect of methanolic extract of annona squamosa on isoniazid rifampicin induced hepatotoxicity in rats. In addition, the absence of antidrug antibodies is not conclusive evidence against an immune mechanism 36. The incidence of hepatotoxicity during antitb treatment is reported to vary 228% 97.
Drug induced liver injury complicates antituberculosis drug treatment and is a leading cause of death worldwide. Hence present study was designed to investigate protective potential of whole plant extract of l. Antihepatotoxic effect of punica granatum acetone extract. Inh induced hepatitis inh h or elevated liver enzymes including hepatitis inh ele was diagnosed based on the clinical. A prospective study of antituberculous drug induced hepatotoxicity in an area endemic for liver diseases. Free radicals are a source for oxidative stress and can act like a domino effect, thus leading to further liver damage. Jcprc5 3 chronological assessment of isoniazid and rifampicin induced hepatotoxicity.
It is a small molecule mw7 that is freely soluble in water. A higher level of free inh might be the cause of the high incidence of liver injury. A prospective study of antituberculous druginduced. Feb 07, 2019 this article focuses on acute isoniazid isonicotinic acid hydrazide inh hepatotoxicity.
Aug 03, 2016 isoniazid inh is highly effective for the management of tuberculosis. Hepatotoxicity was induced by oral administration of inh 50mgkg and rif 100mgkg on every 72hrs for a period of 21days. Since 1952, this agent has been used as a frontline antimicrobial for tuberculosis tb. Isoniazid, rifampicin, gsp method, mannitol, tuberculosis, hepatotoxicity. While acetaminophen is the most common etiology, other offending medications include amoxicillinclavulanic acid, amiodarone, isoniazid, and fluoroquinolones to name a few.
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