Ameliorating diabetes-induced testicular dysfunction by modulating PKC/Nrf2/Bcl-2 signaling: Protective role of sulbutiamine

IF 5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
BioFactors Pub Date : 2024-02-12 DOI:10.1002/biof.2046
Maha Abdelmonem, Shimaa O. Ali, Asmaa K. Al-Mokaddem, Heba R. Ghaiad
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引用次数: 0

Abstract

The prevalence of testicular dysfunction is increasing as it is a common diabetes mellites (DM) complication. The objective of this study is to explore the potential protective effect of sulbutiamine against testicular hypofunction associated with streptozotocin (STZ)-induced DM in rats. Sulbutiamine was administered orally (60 mg/kg) to male Wistar rats for 8 weeks starting 72 h after a single injection of STZ (45 mg/kg, i.p.). Blood glucose level (BGL), serum testosterone level, sperm number, and motility were determined. Testicular tissue was examined histopathologically, and the Johnson score was evaluated. Levels of malondialdehyde (MDA), protein kinase C (PKC), nuclear factor erythroid-derived 2-like 2 (Nrf2), and proliferating cell nuclear antigen (PCNA) were measured. Apoptosis was evaluated by immunohistochemical determination of B-cell lymphoma protein 2 (Bcl-2), Bcl-2 associated X-protein (Bax), and caspase-3. Sulbutiamine administration managed to reduce BGL and boost testicular function as manifested by increased testicular weight, testosterone level, sperm number, and motility compared to the STZ group. Additionally, histopathological examination revealed an improved histological picture and Johnson score of testicular tissue after sulbutiamine treatment. Sulbutiamine administration reduced testicular PKC, MDA, and PCNA levels and increased Nrf2 compared to the untreated group. Moreover, sulbutiamine treatment suppressed apoptosis triggered by STZ as evidenced by elevated Bcl-2, decreased Bax and reduced caspase-3. The present work revealed for the first time a promising protective role of sulbutiamine against STZ-induced testicular dysfunction which may add to the clinical utility of sulbutiamine. The underlying mechanisms involve reducing BGL and PKC, activating Nrf2 and inhibiting apoptosis.

Abstract Image

通过调节 PKC/Nrf2/Bcl-2 信号来改善糖尿病引起的睾丸功能障碍:舒喘宁的保护作用
睾丸功能障碍是一种常见的糖尿病(DM)并发症,其发病率正在不断上升。本研究旨在探讨舒喘宁对链脲佐菌素(STZ)诱导的糖尿病大鼠睾丸功能减退的潜在保护作用。雄性 Wistar 大鼠在单次注射 STZ(45 毫克/千克,静脉注射)72 小时后开始连续 8 周口服舒喘宁(60 毫克/千克)。测定血糖水平(BGL)、血清睾酮水平、精子数量和活力。对睾丸组织进行组织病理学检查,并评估约翰逊评分。测量了丙二醛(MDA)、蛋白激酶 C(PKC)、红细胞衍生核因子 2-like 2(Nrf2)和增殖细胞核抗原(PCNA)的水平。通过免疫组化测定 B 细胞淋巴瘤蛋白 2(Bcl-2)、Bcl-2 相关 X 蛋白(Bax)和 Caspase-3 来评估细胞凋亡。与 STZ 组相比,舒喘宁能降低 BGL 并增强睾丸功能,表现为睾丸重量、睾酮水平、精子数量和活力均有所增加。此外,组织病理学检查显示,舒喘宁治疗后睾丸组织的组织学图像和约翰逊评分均有所改善。与未治疗组相比,舒喘宁能降低睾丸PKC、MDA和PCNA水平,提高Nrf2水平。此外,舒喘宁还抑制了STZ引发的细胞凋亡,表现为Bcl-2升高、Bax降低和caspase-3减少。本研究首次揭示了舒喘宁对STZ诱导的睾丸功能障碍的保护作用,这可能会增加舒喘宁的临床实用性。其基本机制包括降低BGL和PKC、激活Nrf2和抑制细胞凋亡。
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来源期刊
BioFactors
BioFactors 生物-内分泌学与代谢
CiteScore
11.50
自引率
3.30%
发文量
96
审稿时长
6-12 weeks
期刊介绍: BioFactors, a journal of the International Union of Biochemistry and Molecular Biology, is devoted to the rapid publication of highly significant original research articles and reviews in experimental biology in health and disease. The word “biofactors” refers to the many compounds that regulate biological functions. Biological factors comprise many molecules produced or modified by living organisms, and present in many essential systems like the blood, the nervous or immunological systems. A non-exhaustive list of biological factors includes neurotransmitters, cytokines, chemokines, hormones, coagulation factors, transcription factors, signaling molecules, receptor ligands and many more. In the group of biofactors we can accommodate several classical molecules not synthetized in the body such as vitamins, micronutrients or essential trace elements. In keeping with this unified view of biochemistry, BioFactors publishes research dealing with the identification of new substances and the elucidation of their functions at the biophysical, biochemical, cellular and human level as well as studies revealing novel functions of already known biofactors. The journal encourages the submission of studies that use biochemistry, biophysics, cell and molecular biology and/or cell signaling approaches.
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