The Effects of ThymusCaramanicus Jalas Extract and Its Main Constituent Carvacrol Against Cisplatin-Induced Nephrotoxicity in Mice

IF 1.8 4区医学 Q3 PHARMACOLOGY & PHARMACY

Iranian Journal of Pharmaceutical Research Pub Date : 2024-07-03 DOI:10.5812/ijpr-140212

Amin Hassanshahi, Ayat Kaeedi, Mohammad Reza Rahmani, J. Hassanshahi

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引用次数: 0

Abstract

Background: Cisplatin, an anti-cancer chemotherapy drug, has nephrotoxic effects. Thymus caramanicus Jalas (TCJ) has antioxidant effects due to its main components. Objectives: In the current research, we assessed the impact of TCJ extract and its main compound on cisplatin-induced nephrotoxicity in mice. Methods: Forty-two male mice were used in the study. Depending on their group, the animals received saline, carvacrol (10 mg/kg), or TCJ extract (50, 100, and 150 mg/kg) for 10 days. On the fifth day, mice received cisplatin (7.5 mg/kg, i.p.). After 10 days, serum creatinine (Cr) and blood urea nitrogen (BUN) levels were measured. Additionally, malondialdehyde (MDA) and glutathione (GSH) contents, as well as the activity levels of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), and total antioxidant capacity (TAC) were measured in the kidney tissues. The western blotting method was used to determine the kidney's expression of cleaved caspase-3, Bax, Bcl-2, nuclear factor kappa-B (NF-κB), and tumor necrosis factor-alpha (TNF-α). Kidney tissue damage score (KTDS) was assessed using the hematoxylin-eosin (H&E) staining method. Results: Cisplatin significantly increased serum Cr, KTDS, MDA, BUN levels, NF-κB, TNF-α, cleaved caspase-3, and Bax protein expression in the cisplatin group compared to the control group (P < 0.01). Additionally, cisplatin significantly decreased the kidney tissue's TAC and GSH content, activity levels of SOD, catalase, and GPx indicators, and expression of Bcl-2 protein (P < 0.05). TCJ and carvacrol significantly ameliorated these indicators in the cisplatin + TCJ (150 mg/kg) and cisplatin + carvacrol (10 mg/kg) groups compared to the cisplatin group (P < 0.05). Conclusions: TCJ (150 mg/kg) and its main component, carvacrol, could somewhat reduce cisplatin-induced nephrotoxicity through their anti-inflammatory, antioxidant, and anti-apoptotic effects.

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百里香提取物及其主要成分香芹酚对顺铂诱导的小鼠肾毒性的影响

背景：顺铂是一种抗癌化疗药物，具有肾毒性：顺铂是一种抗癌化疗药物，具有肾毒性作用。百里香（Thymus caramanicus Jalas，TCJ）的主要成分具有抗氧化作用。研究目的在当前的研究中，我们评估了TCJ提取物及其主要化合物对顺铂诱导的小鼠肾毒性的影响。研究方法研究使用了 42 只雄性小鼠。根据组别不同，小鼠分别接受生理盐水、香芹酚（10 毫克/千克）或 TCJ 提取物（50、100 和 150 毫克/千克）治疗 10 天。第五天，小鼠接受顺铂（7.5 毫克/千克，静脉注射）治疗。10 天后，测量血清肌酐（Cr）和血尿素氮（BUN）水平。此外，还测量了肾组织中丙二醛（MDA）和谷胱甘肽（GSH）的含量，以及超氧化物歧化酶（SOD）、过氧化氢酶、谷胱甘肽过氧化物酶（GPx）和总抗氧化能力（TAC）的活性水平。用 Western 印迹法测定肾脏中裂解的 caspase-3、Bax、Bcl-2、核因子卡巴-B（NF-κB）和肿瘤坏死因子-α（TNF-α）的表达。肾组织损伤评分（KTDS）采用苏木精-伊红（H&E）染色法进行评估。结果与对照组相比，顺铂组的血清Cr、KTDS、MDA、BUN水平、NF-κB、TNF-α、裂解的caspase-3和Bax蛋白表达均明显升高（P < 0.01）。此外，顺铂还能明显降低肾组织中 TAC 和 GSH 的含量、SOD、过氧化氢酶和 GPx 指标的活性水平以及 Bcl-2 蛋白的表达（P < 0.05）。与顺铂组相比，TCJ 和香芹酚能明显改善顺铂 + TCJ 组（150 毫克/千克）和顺铂 + 香芹酚组（10 毫克/千克）的上述指标（P < 0.05）。结论TCJ（150 毫克/千克）及其主要成分香芹酚可通过抗炎、抗氧化和抗细胞凋亡作用在一定程度上减轻顺铂诱导的肾毒性。

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来源期刊

Iranian Journal of Pharmaceutical Research 医学-药学

CiteScore

3.40

自引率

6.20%

发文量

审稿时长

2 months

期刊介绍： The Iranian Journal of Pharmaceutical Research (IJPR) is a peer-reviewed multi-disciplinary pharmaceutical publication, scheduled to appear quarterly and serve as a means for scientific information exchange in the international pharmaceutical forum. Specific scientific topics of interest to the journal include, but are not limited to: pharmaceutics, industrial pharmacy, pharmacognosy, toxicology, medicinal chemistry, novel analytical methods for drug characterization, computational and modeling approaches to drug design, bio-medical experience, clinical investigation, rational drug prescribing, pharmacoeconomics, biotechnology, nanotechnology, biopharmaceutics and physical pharmacy.