Hassanshahi Amin, Kaeedi Ayat, Rahmani Mohammad Reza, Hassanshahi Jalal
Department of Physiology, School of Medicine, Bam University of Medical Sciences, Bam, Iran.
Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Iran J Pharm Res. 2024 Jul 3;23(1):e140212. doi: 10.5812/ijpr-140212. eCollection 2024 Jan-Dec.
Cisplatin, an anti-cancer chemotherapy drug, has nephrotoxic effects. Jalas (TCJ) has antioxidant effects due to its main components.
In the current research, we assessed the impact of TCJ extract and its main compound on cisplatin-induced nephrotoxicity in mice.
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.
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).
TCJ (150 mg/kg) and its main component, carvacrol, could somewhat reduce cisplatin-induced nephrotoxicity through their anti-inflammatory, antioxidant, and anti-apoptotic effects.
顺铂是一种抗癌化疗药物,具有肾毒性作用。百里香提取物(TCJ)因其主要成分具有抗氧化作用。
在本研究中,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。
本研究使用了42只雄性小鼠。根据分组情况,动物连续10天接受生理盐水、香芹酚(10毫克/千克)或TCJ提取物(50、100和150毫克/千克)。在第5天,小鼠腹腔注射顺铂(7.5毫克/千克)。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)含量,以及超氧化物歧化酶(SOD)、过氧化氢酶和谷胱甘肽过氧化物酶(GPx)的活性水平和总抗氧化能力(TAC)。采用蛋白质免疫印迹法测定肾组织中裂解的半胱天冬酶-3、Bax、Bcl-2、核因子κB(NF-κB)和肿瘤坏死因子-α(TNF-α)的表达。使用苏木精-伊红(H&E)染色法评估肾组织损伤评分(KTDS)。
与对照组相比,顺铂组血清Cr、KTDS、MDA、BUN水平、NF-κB、TNF-α、裂解的半胱天冬酶-3和Bax蛋白表达显著升高(P<0.01)。此外,顺铂显著降低了肾组织的TAC和GSH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和香芹酚在顺铂+TCJ(150毫克/千克)和顺铂+香芹酚(10毫克/千克)组中显著改善了这些指标(P<0.05)。
TCJ(150毫克/千克)及其主要成分香芹酚可通过其抗炎、抗氧化和抗凋亡作用在一定程度上减轻顺铂诱导的肾毒性。