用熊果苷靶向 JAK2/STAT3、NLRP3/Caspase-1 和 PK2/PKR2 通路可改善醋酸铅诱导的大鼠睾丸损伤

Pharmaceuticals Pub Date : 2024-07-08 DOI:10.3390/ph17070909
H. Arab, Shuruq E. Alsufyani, Ahmed M. Ashour, Amany M Gad, A. Elhemiely, Mohamed H. A. Gadelmawla, Marwa Ahmed Mahmoud, Ali Khames
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引用次数: 0

摘要

铅(Pb)是一种有毒重金属,会对雄性动物的生殖系统产生不利影响。本研究考察了熊果苷(一种前景看好的对苯二酚苷)对铅诱导的大鼠睾丸损伤的潜在改善作用。连续 10 天腹腔注射醋酸铅(20 毫克/千克/天)诱导大鼠睾丸损伤。36 只大鼠被分为 6 个实验组(每组 6 只):对照组、口服熊果苷(250 毫克/千克)治疗的对照组、腹腔注射熊果苷(75 毫克/千克)治疗的对照组、未经处理的 Pb 组、口服熊果苷治疗的 Pb 组和腹腔注射熊果苷治疗的 Pb 组。每天给药,连续 10 天。熊果苷通过口服和腹腔注射两种途径给药,以比较这两种途径在缓解醋酸铅引起的睾丸功能障碍方面的效果。目前的数据显示,口服和腹腔注射熊果苷都能显著提高血清睾酮和精子数量/活力,表明睾丸功能障碍得到了改善。同时,这两种途径都能降低睾丸组织病理学畸变和约翰森损伤评分。降低脂质过氧化反应、增加谷胱甘肽和过氧化氢酶抗氧化剂证明,睾丸氧化应激受到抑制,从而产生了这些有利的结果。此外,熊果苷还降低了睾丸的p-JAK2和p-STAT3水平,证实了对JAK2/STAT3促炎途径的抑制作用。与此同时,熊果苷还抑制了睾丸NLRP3/caspase-1/NF-B轴,并增强了细胞保护PK2/PKR2途径。值得注意的是,与口服相比,低剂量腹腔注射熊果苷能更明显地缓解铅诱导的睾丸功能障碍。总之,熊果苷可通过刺激睾丸抗氧化剂和PK2/PKR2途径,抑制JAK2/STAT3和NLRP3/caspase-1促炎途径,从而改善铅诱发的睾丸损伤。因此,熊果苷可用作减轻铅诱导的睾丸损伤的辅助药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeting JAK2/STAT3, NLRP3/Caspase-1, and PK2/PKR2 Pathways with Arbutin Ameliorates Lead Acetate-Induced Testicular Injury in Rats
The reproductive system of males is adversely impacted by lead (Pb), a toxic heavy metal. The present study examined arbutin, a promising hydroquinone glycoside, for its potential ameliorative impact against Pb-induced testicular impairment in rats. The testicular injury was induced by the intraperitoneal administration of Pb acetate (20 mg/kg/day) for 10 consecutive days. Thirty-six rats were divided into six experimental groups (n = 6 per group): control, control treated with oral arbutin (250 mg/kg), control treated with intraperitoneal arbutin (75 mg/kg), untreated Pb, Pb treated with oral arbutin, and Pb treated with intraperitoneal arbutin. The treatments were administered daily for 10 days. Arbutin was administered by the oral and intraperitoneal routes to compare the efficacy of both routes in mitigating Pb acetate-induced testicular dysfunction. The current data revealed that both oral and intraperitoneal administration of arbutin significantly enhanced serum testosterone and sperm count/motility, indicating the amelioration of testicular dysfunction. In tandem, both routes lowered testicular histopathological aberrations and Johnsen’s damage scores. These favorable outcomes were driven by dampening testicular oxidative stress, evidenced by lowered lipid peroxidation and increased glutathione and catalase antioxidants. Moreover, arbutin lowered testicular p-JAK2 and p-STAT3 levels, confirming the inhibition of the JAK2/STAT3 pro-inflammatory pathway. In tandem, arbutin suppressed the testicular NLRP3/caspase-1/NF-B axis and augmented the cytoprotective PK2/PKR2 pathway. Notably, intraperitoneal arbutin at a lower dose prompted a more pronounced mitigation of Pb-induced testicular dysfunction compared to oral administration. In conclusion, arbutin ameliorates Pb-evoked testicular damage by stimulating testicular antioxidants and the PK2/PKR2 pathway and inhibiting the JAK2/STAT3 and NLRP3/caspase-1 pro-inflammatory pathways. Hence, arbutin may be used as an adjunct agent for mitigating Pb-induced testicular impairment.
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