Herbo-vitamin medicine Livogrit Vital ameliorates isoniazid induced liver injury (IILI) in human liver (HepG2) cells by decreasing isoniazid accumulation and oxidative stress driven hepatotoxicity.

IF 3.3 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE BMC Complementary Medicine and Therapies Pub Date : 2024-11-08 DOI:10.1186/s12906-024-04685-x
Acharya Balkrishna, Vivek Gohel, Meenu Tomer, Rishabh Dev, Anurag Varshney
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Abstract

Background: Tuberculosis (TB) is a leading cause of infection related mortality. Isoniazid is one of the frontline drugs for anti-TB therapy. Hepatotoxicity induced by isoniazid is a major cause of drug-discontinuation which may lead to development of resistant TB or increased mortality.

Purpose: To characterize pharmacological properties of plant-based prescription medicine, Livogrit Vital (LVV) against isoniazid-induced liver injury (IILI) using HepG2 cells.

Method: Phytometabolite characterization of LVV was performed by High-performance liquid chromatography (HPLC). The effects of LVV on cytosafety, IC50 shift, oxidative stress, ER stress, apoptosis, liver injury markers, and accumulation of isoniazid and hydrazine was performed on HepG2 cells induced with isoniazid. Silymarin was used as the positive control.

Results: HPLC based phytometabolite characterization of LVV revealed the presence of several anti-oxidant, anti-apoptotic, and hepatoprotective compounds. In isoniazid-induced HepG2 cells, LVV reduced cytotoxicity of isoniazid and shifted its IC50 value. Treatment with LVV reduced ROS generation and lipid peroxidation; enhanced GSH enzyme levels in isoniazid-induced HepG2 cells. As per the mechanistic evaluation, LVV modulated gene expression level of Caspase-3, FGF21, and IRE-1α. LVV treatment also normalized isoniazid-induced elevated Caspase-3 activity and cPARP1 protein levels, indicating its potentials to regulate liver cell apoptosis. Concomitantly, biomarkers of hepatotoxicity, ALT and GGT, also decreased by LVV treatment. Interestingly, LVV treatment reduced intracellular accumulation of isoniazid and its toxic metabolite hydrazine, in isoniazid-stimulated HepG2 cells.

Conclusion: Treatment of hepatic cells with the herbo-vitamin medicine, Livogrit Vital, regulates IILI by modulation of oxidative and ER stress, apoptosis, and bioaccumulation of isoniazid and hydrazine. Collectively, Livogrit Vital could well be explored as an adjuvant hepatoprotective agent alongwith anti-TB medicines.

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草本维生素药物 Livogrit Vital 可通过减少异烟肼积累和氧化应激驱动的肝毒性,改善人类肝脏(HepG2)细胞中异烟肼诱导的肝损伤(IILI)。
背景:结核病(TB)是与感染有关的主要死亡原因。异烟肼是抗结核治疗的一线药物之一。目的:使用 HepG2 细胞研究植物处方药 Livogrit Vital(LVV)抗异烟肼诱导的肝损伤(IILI)的药理特性:方法:采用高效液相色谱法(HPLC)对 LVV 的植物代谢物进行表征。方法:采用高效液相色谱法(HPLC)对 LVV 植物代谢物进行了表征,并对异烟肼诱导的 HepG2 细胞进行了细胞安全性、IC50 值变化、氧化应激、ER 应激、细胞凋亡、肝损伤标志物以及异烟肼和肼积累的影响研究。水飞蓟素作为阳性对照:结果:基于高效液相色谱法的植物代谢物表征显示,LVV 中含有多种抗氧化、抗凋亡和保肝化合物。在异烟肼诱导的 HepG2 细胞中,LVV 可降低异烟肼的细胞毒性并改变其 IC50 值。在异烟肼诱导的 HepG2 细胞中,LVV 可减少 ROS 的产生和脂质过氧化反应;提高 GSH 酶的水平。根据机理评估,LVV 可调节 Caspase-3、FGF21 和 IRE-1α 的基因表达水平。LVV还能使异烟肼诱导的Caspase-3活性升高和cPARP1蛋白水平正常化,这表明LVV具有调节肝细胞凋亡的潜力。与此同时,肝毒性的生物标志物谷丙转氨酶和谷草转氨酶也因 LVV 治疗而下降。有趣的是,在异烟肼刺激的 HepG2 细胞中,LVV 处理可减少异烟肼及其毒性代谢产物肼的细胞内积累:结论:用草本维生素药物 Livogrit Vital 处理肝细胞,可通过调节氧化和 ER 应激、细胞凋亡以及异烟肼和肼的生物蓄积来调节 IILI。总之,Livogrit Vital 完全可以作为一种辅助性保肝药物与抗结核药物一起使用。
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来源期刊
BMC Complementary Medicine and Therapies
BMC Complementary Medicine and Therapies INTEGRATIVE & COMPLEMENTARY MEDICINE-
CiteScore
6.10
自引率
2.60%
发文量
300
审稿时长
19 weeks
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