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哈尔明通过抗氧化、抗炎和抗凋亡作用减轻顺铂诱导的雄性小鼠肾损伤。

Harmine mitigates cisplatin-induced renal injury in male mice through antioxidant, anti-inflammatory, and anti-apoptosis effects.

作者信息

Ghanbari Ali, Jalili Cyrus, Salahshoor Mohammad Reza, Javanmardy Setareh, Ravankhah Saeed, Akhshi Nasim

机构信息

Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.

Department of Anatomical Sciences, Medical School, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.

出版信息

Res Pharm Sci. 2022 Jul 14;17(4):417-427. doi: 10.4103/1735-5362.350242. eCollection 2022 Aug.

Abstract

BACKGROUND AND PURPOSE

Cisplatin is a chemotherapeutic drug used to treat cancer, however, causes kidney toxicity. Harmine is a plant-derived alkaloid with a wide range of therapeutic applications. The effects of harmine on the renal side effects of cisplatin in mice were studied in this study.

EXPERIMENTAL APPROACH

Forty-eight male BALB/c mice were randomly divided into eight groups (n = 6). They were treated with saline, cisplatin (5.5 mg/kg), harmine (5, 10, and 15 mg/kg/day), cisplatin + harmine (5, 10, and 15 mg/kg/day), respectively. All administrations were done daily and intraperitoneally for 4 days. The criteria related to histology, oxidation, anti-oxidation, inflammation, and apoptosis of renal tissue were evaluated.

FINDINGS / RESULTS: There was a significant decrease in total antioxidant capacity of renal tissue, renal corpuscles diameter, and expression level in the cisplatin group than in the control group, while the values of these parameters were significantly similar to the control group in the moderate or high doses of harmine + cisplatin groups. There were significant increases in serum urea and creatinine levels, bowman space, the amounts of malondialdehyde, apoptosis rate, and TNF-α, NF-κB, IL-1β, and caspase-3 gene expressions in kidney tissue of the cisplatin group compared to the control group, while these criteria did not differ in the moderate or high doses of harmine + cisplatin groups.

CONCLUSION AND IMPLICATIONS

Harmine protected the kidneys against cisplatin-induced damage. Antioxidant, anti-inflammatory, and anti-apoptotic harmine properties were involved in this healing effect.

摘要

背景与目的

顺铂是一种用于治疗癌症的化疗药物,但会导致肾脏毒性。哈尔明是一种植物来源的生物碱,具有广泛的治疗应用。本研究探讨了哈尔明对顺铂所致小鼠肾脏副作用的影响。

实验方法

将48只雄性BALB/c小鼠随机分为8组(n = 6)。分别给予生理盐水、顺铂(5.5 mg/kg)、哈尔明(5、10和15 mg/kg/天)、顺铂+哈尔明(5、10和15 mg/kg/天)处理。所有给药均每日腹腔注射,持续4天。评估与肾组织组织学、氧化、抗氧化、炎症和凋亡相关的指标。

研究结果

与对照组相比,顺铂组肾组织总抗氧化能力、肾小体直径和表达水平显著降低,而在中高剂量哈尔明+顺铂组中,这些参数的值与对照组显著相似。与对照组相比,顺铂组小鼠血清尿素和肌酐水平、鲍曼间隙、丙二醛含量、凋亡率以及肾组织中TNF-α、NF-κB、IL-1β和caspase-3基因表达显著升高,而在中高剂量哈尔明+顺铂组中这些指标无差异。

结论与意义

哈尔明可保护肾脏免受顺铂诱导的损伤。抗氧化、抗炎和抗凋亡特性参与了这种保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e02/9400464/6748330a3726/RPS-17-417-g001.jpg

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