Functional Genomics Laboratory, Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, 45550,Pakistan.
Translational Genomics Laboratory, Department of Biosciences, COMSATS University, Islamabad (CUI), Islamabad, 45550,Pakistan.
Curr Pharm Biotechnol. 2022;23(1):158-170. doi: 10.2174/1389201022666210203142138.
Carbon tetrachloride (CCl4) is a dynamic environmental toxin released from chemical factories and its concentration in the atmosphere is accelerating at an alarming proportion. The potential presence of CCl4 in the human body causes liver injury via free radical stimulated inflammatory responses.
In this study, protective effects of hydromethanolic seeds extract of Prunus persica (PPHM) were evaluated for free radical scavenging potential in CCl4 mediated acute liver toxicity in the murine model.
Followed by acute oral toxicity analysis, liver cells of Sprague-Dawley (SD) rats were treated with CCl4 and subsequently, the chemoprophylactic effect of extract (400 mg/Kg dose) was evaluated using in vivo studies including, silymarin as the positive control. Biochemical parameters, staining (hematoxylin and eosin (H & E) and Masson's Trichome) and quantitative gene expression analysis via real-time PCR were used to evaluate hepatic damage control.
The results illustrated that PPHM extract exhibit strong anti-oxidant activity, comparable to the positive control, gallic acid. Research study results also demonstrated that the extract treatment at 400 mg/Kg concentration is highly effective in protecting liver damage due to CCl4 exposure. Mechanistic investigations indicated that the therapeutic action of PPHM was correlated with the increase in Nrf2, NQO-1 and decrease in collagen III mRNA genes expression compared to CCl4 treated group.
Accordingly, our research study indicated that PPHM alleviated CCl4-mediated oxidative stress through Nrf2/NQO-1 pathway, thereby protecting liver damage against environmental toxins. Our findings provide supportive evidence to suggest PPHM as a novel nontoxic hepatoprotective agent.
四氯化碳(CCl4)是一种从化工厂释放的动态环境毒素,其在大气中的浓度正以惊人的比例加速上升。CCl4 存在于人体内会通过自由基刺激炎症反应导致肝损伤。
本研究评估了桃 Prunus persica 的水甲醇种子提取物(PPHM)在 CCl4 介导的急性肝毒性的小鼠模型中清除自由基的潜力,以评估其保护作用。
在进行急性口服毒性分析后,用 CCl4 处理 Sprague-Dawley(SD)大鼠的肝细胞,随后通过体内研究评估提取物(400mg/kg 剂量)的化学预防作用,其中以水飞蓟素作为阳性对照。使用生化参数、染色(苏木精和伊红(H&E)和 Masson 三色)和实时 PCR 进行定量基因表达分析,以评估肝损伤控制。
结果表明,PPHM 提取物表现出很强的抗氧化活性,可与阳性对照物没食子酸相媲美。研究结果还表明,以 400mg/kg 浓度进行的提取物处理在保护 CCl4 暴露引起的肝损伤方面非常有效。机制研究表明,与 CCl4 处理组相比,PPHM 的治疗作用与 Nrf2、NQO-1 的增加和胶原 III mRNA 基因表达的减少相关。
因此,我们的研究表明,PPHM 通过 Nrf2/NQO-1 途径减轻了 CCl4 介导的氧化应激,从而保护肝脏免受环境毒素的损伤。我们的研究结果提供了支持性证据,表明 PPHM 作为一种新型无毒肝保护剂。