Induction of Heme oxygenase 1 protects hepatocytes from Isoniazid – Rifampicin induced cell death: an in vitro study

Bishnu, Debasree

doi:10.7869/tg.316

Cited by 3 publications

(4 citation statements)

References 18 publications

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“…NQO1 reduced RIF‐Q to RIF and mediated the redox cycle of RIF‐Q‐induced ROS formation and caused cytotoxicity in HepG2 cells . These findings indicated that HO‐1 and NQO1 may play major roles in responding to oxidative stress and alleviating injury caused by ROS, which may at least partly contribute to the underlying pathogenesis of ATLI …”

Section: What Is Known and Objectivementioning

confidence: 93%

“…Heme oxygenase 1 (HO‐1, encoded by the HMOX1 gene) is a phase II antioxidant enzyme that is primarily involved in detoxification, and NRF2 knockdown reduces the basal level of HO‐1 expression . Coadministration of INH and RIF in HepG2 cells could induce expression of the cytoplasmic HO‐1 protein during early hours of drug treatment with minimum loss of cell viability and cell death, and induction of HO‐1 by hemin chloride could ameliorate INH‐RIF‐induced hepatocyte cell death . Sagittaria sagittifolia L. polysaccharide (SSP) significantly alleviated the hepatotoxicity induced by coadministration of INH and RIF in mice, which was mainly attributed to an increase in the gene and protein expression of NRF2 and its downstream enzymes HO‐1 induced by SSP .…”

Section: What Is Known and Objectivementioning

confidence: 99%

“…17 These findings indicated that HO-1 and NQO1 may play major roles in responding to oxidative stress and alleviating injury caused by ROS, which may at least partly contribute to the underlying pathogenesis of ATLI. 9,14 Polymorphisms in genes of the oxidative stress pathway could affect their antioxidant functions. Association studies have shown that genetic variants in the antioxidant signalling pathway may be involved in ATLI in Japanese patients.…”

Section: What Is K Nown and Objec Tivementioning

confidence: 99%

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Possible association of HMOX1 and NQO1 polymorphisms with anti-tuberculosis drug-induced liver injury: A matched case-control study

et al. 2019

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Summary What is known and objective Reactive metabolites from anti‐tuberculosis (anti‐TB) drugs can result in abnormal accumulation of reactive oxygen species (ROS), which plays an important role in anti‐TB drug‐induced liver injury (ATLI). Liver cells could keep the production of ROS in balance by antioxidant activities. The heme oxygenase 1, encoded by the HMOX1 gene and NADH:quinone oxidoreductase 1, encoded by the NQO1 gene are crucial mediators of cellular defense against ROS. The present study aimed to investigate the associations between HMOX1 and NQO1 polymorphisms and ATLI in Chinese anti‐TB treatment population. Methods A matched case‐control study was conducted using 314 ATLI cases and 628 controls. Multivariate conditional logistic regression analysis was used to estimate the association between genotypes and risk of ATLI by the odds ratios (ORs) with 95% confidence intervals (CIs), with weight and use of hepatoprotectant as covariates. Results and discussion Patients carrying the GG genotype at rs2071748 in HMOX1 were at a higher risk of ATLI than those with the AA genotype (adjusted OR = 1.503, 95% CI: 1.005‐2.249, P = 0.047), and significant differences were also found under the recessive (P = 0.015) and additive (P = 0.045) models. Subgroup analysis confirmed the relationship in mild hepatotoxicity cases under the recessive and additive models (adjusted OR = 1.714, 95% CI: 1.169‐2.513, P = 0.006; adjusted OR = 1.287, 95% CI: 1.015‐1.631, P = 0.037, respectively). What is new and conclusion This is the first study to explore the relationship between HMOX1, NQO1 polymorphisms and ATLI in Chinese anti‐TB treatment population. Based on a matched case‐control study, genetic polymorphisms of HMOX1 may be associated with susceptibility to ATLI in the Chinese population.

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Section: What Is Known and Objectivementioning

confidence: 93%

Section: What Is Known and Objectivementioning

confidence: 99%

Section: What Is K Nown and Objec Tivementioning

confidence: 99%

See 1 more Smart Citation

Possible association of HMOX1 and NQO1 polymorphisms with anti-tuberculosis drug-induced liver injury: A matched case-control study

et al. 2019

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“…These reactive metabolites could induce the production of excessive reactive oxygen species (ROS), leading to lipid peroxidation and cell death (115). Otterbein et al, have demonstrated that co-administration of Isoniazid (INH) and rifampin (RIF) to HepG2 cells could induce expression of the cytoplasmic HO-1 protein during the early hours of drug treatment, with minimum loss of cell viability and cell death, and induction of HO-1 by hemin chloride could reverse the drug induced liver injury (116). This could be a potential target for a future therapeutic option to counteract INH-RIF drug-induced liver injury.…”

Section: The Modulators and Inducers Of Ho-1mentioning

confidence: 99%

A Dual Role of Heme Oxygenase-1 in Tuberculosis

Yang

Ouyang

et al. 2022

Front. Immunol.

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Iron metabolism is vital for the survival of both humans and microorganisms. Heme oxygenase-1 (HO-1) is an essential stress-response enzyme highly expressed in the lungs, and catabolizes heme into ferrous iron, carbon monoxide (CO), and biliverdin (BV)/bilirubin (BR), especially in pathological conditions which cause oxidative stress and inflammation. Ferrous iron (Fe2+) is an important raw material for the synthesis of hemoglobin in red blood cells, and patients with iron deficiency are often associated with decreased cellular immunity. CO and BR can inhibit oxidative stress and inflammation. Thus, HO-1 is regarded as a cytoprotective molecule during the infection process. However, recent study has unveiled new information regarding HO-1. Being a highly infectious pathogenic bacterium, Mycobacterium tuberculosis (MTB) infection causes acute oxidative stress, and increases the expression of HO-1, which may in turn facilitate MTB survival and growth due to increased iron availability. Moreover, in severe cases of MTB infection, excessive reactive oxygen species (ROS) and free iron (Fe2+) due to high levels of HO-1 can lead to lipid peroxidation and ferroptosis, which may promote further MTB dissemination from cells undergoing ferroptosis. Therefore, it is important to understand and illustrate the dual role of HO-1 in tuberculosis. Herein, we critically review the interplay among HO-1, tuberculosis, and the host, thus paving the way for development of potential strategies for modulating HO-1 and iron metabolism.

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Heme Oxygenase-1 and Hemopexin Gene Polymorphisms and the Risk of Anti-Tuberculosis Drug-Induced Hepatotoxicity in China

Liu

Pan

et al. 2022

Pharmacogenomics

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Objective: To assess whether the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH) might be influenced by haem oxygenase-1 ( HMOX1) and haemopexin ( HPX) gene polymorphisms. Methods: A dynamic anti-tuberculosis treatment cohort was constructed, and the 1:4 matched nested case–control study was analysed. Eight single nucleotide polymorphisms (SNPs) of the two genes were selected for genotyping and Bonferroni correction was performed to correct for multiple comparison. Results: Overall, 7.8% of patients developed ATDH. SNP rs1807714 in the HMOX1 gene had decreased effects on the risk of moderate and severe hepatotoxicity under the dominant and additive models, and hepatocellular injury under the additive model. SNP rs2682099 in the HPX gene had increased effects on the risk of moderate and severe hepatotoxicity under the recessive model. However, these associations disappeared after Bonferroni correction. Conclusion: HMOX1 and HPX gene polymorphisms might not be associated with susceptibility to ATDH in the Chinese population.

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Induction of Heme oxygenase 1 protects hepatocytes from Isoniazid – Rifampicin induced cell death: an in vitro study

Cited by 3 publications

References 18 publications

Possible association of HMOX1 and NQO1 polymorphisms with anti-tuberculosis drug-induced liver injury: A matched case-control study

Possible association of HMOX1 and NQO1 polymorphisms with anti-tuberculosis drug-induced liver injury: A matched case-control study

A Dual Role of Heme Oxygenase-1 in Tuberculosis

Heme Oxygenase-1 and Hemopexin Gene Polymorphisms and the Risk of Anti-Tuberculosis Drug-Induced Hepatotoxicity in China

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