Relationship of anti-tuberculosis drug-induced liver injury and genetic polymorphisms in CYP2E1 and GST

Santos, Eliana Abreu; Gonçalves, José Carlos Saraiva; Fleury, Marcos K.; Kritski, Afrânio Lineu; Oliveira, Martha Maria de; Velasque, Luciane; Silva, José Roberto Lapa e; Estrela, Rita de Cássia Elias

doi:10.1016/j.bjid.2019.09.003

Cited by 13 publications

(9 citation statements)

References 21 publications

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“…The proportion of GSTT1 null-type in our research was 34.3%. This was consistent with the proportion of GSTT1 null-type in India (11.8%) and Brazil (22%) [11], [12].…”

Section: Discussionsupporting

confidence: 88%

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Hepatic Injury and Glutathione s-transferase Deletion Related to Antituberculosis Use: An Observational Study in Balinese Population, Indonesia

Artana¹,

Artini²,

Ngurah³

et al. 2020

Open Access Maced J Med Sci

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BACKGROUND: Glutathione S-transferase (GST), together with other drug-metabolizing enzymes (N-acetyltransferase and cytochrome P450), plays a crucial role in the metabolism of isoniazid (isonicotinic acid hydrazide). Among five isoforms of GST, GSTM1, and GSTT1 had been proved to involve in isoniazid metabolism. AIM: We aimed to investigate association between GST deletion and hepatic injury in the Indonesian population. METHODS: This is a cross-sectional study. The total participants’ number was 70. Our whole blood samples were collected from adult pulmonary tuberculosis patients who received antituberculosis treatment category one in Bali. Detection for GSTM1 and GSTT1 deletion performed with the polymerase chain reaction technique using internal standard β-globin. Data analysis performed with the Chi-square test. RESULTS: The proportion of GSTM1 null was 71.4% whereas the GSTT1 null was 34.3%. The proportion of combined GSTM1 null and GSTT1 null was 22.9%. There was no significant difference in liver damage incidence between GSTM1 null and wild-type (p > 0.005). There was also no significant difference in liver damage incidence between GSTT1 null and wild-type (p > 0.005). CONCLUSIONS: Neither GSTM1 nor GSTT1 deletion proved to be associated with liver injury regarding antituberculosis use.

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“…The proportion of GSTT1 null-type in our research was 34.3%. This was consistent with the proportion of GSTT1 null-type in India (11.8%) and Brazil (22%) [11], [12].…”

Section: Discussionsupporting

confidence: 88%

“…However, some studies revealed different results. The proportion of null-type GSTM1 on research done by Teixeira et al [10] and Santos et al [11] in Brazil, and also by Gupta et al [12] in India, was lower than wild-type GSTM1. The difference is highly related to the race variation among populations.…”

Section: Discussionmentioning

confidence: 79%

Hepatic Injury and Glutathione s-transferase Deletion Related to Antituberculosis Use: An Observational Study in Balinese Population, Indonesia

Artana¹,

Artini²,

Ngurah³

et al. 2020

Open Access Maced J Med Sci

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“…: 1.13-5.39, P = 0.02) (Huang et al, 2007). In addition, GSTT1 null carriers showed higher risk of anti-TB DILI in small Brazilian population (n = 43) (Santos et al, 2019).…”

Section: Two Independent Studies On Dose Optimization Of Inh Based On...mentioning

confidence: 88%

Novel Clinical Biomarkers for Drug-Induced Liver Injury

Chen

Guan

et al. 2021

Drug Metab Dispos

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Drug-induced liver injury (DILI) remains a critical clinical issue and has been a treatment challenge nowadays as it was in the past. However, the traditional biomarkers or indicators are insufficient to predict the risks and outcome of patients with DILI due to its poor specificity and sensitivity. Recently, the development of high-throughput technologies, especially omics and multi-omics has sparked growing interests in identification of novel clinical DILI biomarkers, many of which also provide a mechanistic insight. Accordingly, in this mini-review, we summarize recent advances in novel clinical biomarkers for DILI prediction, diagnosis and prognosis and highlight the limitations or challenges involved in biomarker discovery or their clinical translation. Although huge work has been done, most reported biomarkers lack comprehensive information and more specific DILI biomarkers are still needed to complement the traditional biomarkers such as ALT or AST in clinical decision making.

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“…CYP2E1 is highly polymorphic, in which the CYP2E1 c1/c1 genotype had a higher CYP2E1 activity. A study showed that the patients with CYP2E1 c1/c1 had a 4.57-fold higher risk of hepatotoxicity than other patients ( Santos et al, 2019 ). Therefore, CYP2E1 c1/c1 might be a risk factor for the increased incidence of hepatotoxicity in INH.…”

Section: The Molecular Mechanism Involved In Isoniazid-induced Liver ...mentioning

confidence: 99%

Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: A review

Zhuang

Liu

et al. 2022

Front. Pharmacol.

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Isoniazid (INH) and rifampicin (RFP) are the first-line medications for tuberculosis treatment, and liver injury is the major adverse effect. Natural medicinal ingredients provide distinct benefits in alleviating patients’ symptoms, lowering the liver injury risk, delaying disease progression, and strengthening the body’s ability to heal. This paper summarises the recent research on the mechanisms of INH and RFP-induced liver injury and the effects of natural medicinal ingredients. It is believed that INH-induced liver injury may be attributed to oxidative stress, mitochondrial dysfunction, drug metabolic enzymes, protoporphyrin IX accumulation, endoplasmic reticulum stress, bile transport imbalance, and immune response. RFP-induced liver injury is mainly related to cholestasis, endoplasmic reticulum stress, and liver lipid accumulation. However, the combined effect of INH and RFP on liver injury risk is still uncertain. RFP can increase INH-induced hepatotoxicity by regulating the expression of drug-metabolizing enzymes and transporters. In contrast, INH can antagonize RFP-induced liver injury by reducing the total bilirubin level in the blood. Sagittaria sagittifolia polysaccharide, quercetin, gallic acid, and other natural medicinal ingredients play protective roles on INH and RFP-induced liver injury by enhancing the body’s antioxidant capacity, regulating metabolism, inhibiting cell apoptosis, and reducing the inflammatory response. There are still many gaps in the literature on INH and RFP-induced liver injury mechanisms and the effects of natural medicinal ingredients. Thus, further research should be carried out from the perspectives of liver injury phenotype, injury markers, in vitro and in vivo liver injury model construction, and liver-gut axis. This paper comprehensively reviewed the literature on mechanisms involved in INH and RFP-induced liver injury and the status of developing new drugs against INH and RFP-induced liver injury. In addition, this review also highlighted the uses and advantages of natural medicinal ingredients in treating drug-induced liver injury.

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Relationship of anti-tuberculosis drug-induced liver injury and genetic polymorphisms in CYP2E1 and GST

Cited by 13 publications

References 21 publications

Hepatic Injury and Glutathione s-transferase Deletion Related to Antituberculosis Use: An Observational Study in Balinese Population, Indonesia

Hepatic Injury and Glutathione s-transferase Deletion Related to Antituberculosis Use: An Observational Study in Balinese Population, Indonesia

Novel Clinical Biomarkers for Drug-Induced Liver Injury

Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: A review

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