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抗结核药物性肝损伤过程中循环 microRNAs 122 和 192 的表达变化表明其作为潜在生物标志物的作用。

Altered expressions of circulating microRNAs 122 and 192 during antitubercular drug induced liver injury indicating their role as potential biomarkers.

机构信息

Department of Biochemistry, 29751Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Department of Biochemistry, All India Institute of Medical Sciences, Raebareli, Uttar Pradesh, India.

出版信息

Hum Exp Toxicol. 2021 Sep;40(9):1474-1484. doi: 10.1177/0960327121997975. Epub 2021 Mar 17.

DOI:10.1177/0960327121997975
PMID:33729026
Abstract

Drug induced liver toxicity is a serious health complication leading to high mortality rates and post marketing withdrawal of drugs. Although considered to be the gold standard biomarkers; aspartate aminotransferase, alanine aminotransferase, total bilirubin and alkaline phosphatase have been found to have specificities beyond liver, therefore more specific and predictive markers for the detection of antitubercular drug mediated liver damage are required. Unfortunately, the effectiveness of currently used first line antitubercular drugs namely isoniazid, rifampicin, pyrazinamide is often accompanied with liver injury, impeding the cure of patients. Keeping in view, the prognostic and diagnostic applications of microRNAs in various diseases, we tried to assess the importance of microRNAs 122 and 192 in antitubercular drug associated liver injuries. The study included subjects having tuberculosis of any type with antitubercular drug induced liver injury; naïve or newly diagnosed tuberculosis patients, tuberculosis patients on drugs not having toxicity and healthy controls. Observations from this study revealed that expression levels of miR-122 and miR-192 were significantly decreased in the serum of antitubercular drug induced liver injury patients only. Therefore, these microRNAs or the pathways associated with them can be used as a tool to predict or cure antitubercular drug associated liver injury in future.

摘要

药物性肝毒性是一种严重的健康并发症,可导致高死亡率和药物上市后撤市。虽然天门冬氨酸氨基转移酶、丙氨酸氨基转移酶、总胆红素和碱性磷酸酶被认为是金标准生物标志物;但已发现它们具有超出肝脏的特异性,因此需要更特异和可预测的生物标志物来检测抗结核药物介导的肝损伤。不幸的是,目前使用的一线抗结核药物(异烟肼、利福平、吡嗪酰胺)的有效性常常伴随着肝损伤,阻碍了患者的治愈。鉴于 microRNAs 在各种疾病中的预后和诊断应用,我们试图评估 microRNAs 122 和 192 在抗结核药物相关肝损伤中的重要性。该研究包括患有任何类型结核病和抗结核药物性肝损伤的患者;初治或新诊断的结核病患者、无毒性药物治疗的结核病患者和健康对照者。这项研究的观察结果表明,miR-122 和 miR-192 的表达水平仅在抗结核药物性肝损伤患者的血清中显著降低。因此,这些 microRNAs 或与之相关的途径可以用作预测或治疗抗结核药物相关肝损伤的工具。

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