Alogliptin attenuates testicular damage induced by monosodium glutamate in both juvenile and adult male rats by activating autophagy: ROS dependent AMPK/mTOR

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology Pub Date : 2024-12-24 DOI:10.1016/j.reprotox.2024.108826

Manal Mohammad Morsy , Heba A. Hassan , Reham M. Morsi , Ola Elsayed Nafea , Azza I. Farag , Rania Saad Ramadan

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引用次数: 0

Abstract

Monosodium glutamate (MSG) is one of the most commonly used food additives, known for its adverse health effects. Alogliptin (ALO) is a highly selective dipeptidyl peptidase-4 inhibitor, but its role in male reproductive function remains debated. The study was designed to evaluate and compare the potential of ALO in mitigating MSG-induced testicular toxicity in juvenile and adult male rats. Juvenile and adult male rats were treated with either MSG or pretreated with ALO before MSG administration. The rats then received ALO and MSG concurrently for 28 days. Testicular tissues were isolated and subjected to histo-biochemical and molecular assessments. Our results demonstrated that ALO reversed MSG-induced testicular injury, as evidenced by the restoration of reproductive hormone balance (increased serum luteinizing hormone and testosterone concentrations), suppression of oxidative stress injury (decreased testicular malondialdehyde, increased superoxide dismutase activity, and minimal 8-hydroxy-2′-deoxyguanosine immunoreactivity), inflammation (reduced testicular tumor necrosis factor-alpha levels), and fibrosis (decreased testicular collagen fiber deposition). Additionally, ALO impeded apoptosis and activated autophagy by decreasing caspase-3 activity, stimulating the AMPK/mTOR pathway, downregulating Bax and SQSTM-1/p62 expression, upregulating Bcl2 and Beclin 1, promoting testicular proliferation (increased number of proliferating cell nuclear antigen-positive cells in the testis), restoring glycogen content in the testis (mild to moderate periodic acid-Schiff reaction), and preserving testicular architecture. MSG induced more severe adverse testicular effects in juvenile rats, while ALO pretreatment was more protective in adult rats. ALO's anti-inflammatory, antioxidant, antiapoptotic, pro-autophagic, antifibrotic, and proliferative actions in the testis suggest its promising potential for combating male reproductive dysfunction.

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阿格列汀通过激活自噬：ROS依赖性AMPK/mTOR，减轻幼年和成年雄性大鼠味精诱导的睾丸损伤。

味精（MSG）是最常用的食品添加剂之一，因其对健康的不良影响而闻名。阿格列汀（ALO）是一种高选择性二肽基肽酶-4抑制剂，但其在男性生殖功能中的作用仍存在争议。本研究旨在评估和比较ALO在减轻味精诱导的幼年和成年雄性大鼠睾丸毒性方面的潜力。幼年和成年雄性大鼠在给药前分别给予味精或ALO预处理。随后，大鼠同时接受ALO和味精同时治疗28天。分离睾丸组织，进行组织生化和分子评价。我们的研究结果表明，ALO逆转了msg诱导的睾丸损伤，证明了恢复生殖激素平衡（增加血清黄体生成素和睾酮浓度），抑制氧化应激损伤（降低睾丸丙二醛，增加超氧化物歧化酶活性，降低8-羟基-2'-脱氧鸟苷免疫反应性），炎症（降低睾丸肿瘤坏死因子- α水平）。纤维化（睾丸胶原纤维沉积减少）。此外，ALO通过降低caspase-3活性，刺激AMPK/mTOR通路，下调Bax和SQSTM-1/p62表达，上调Bcl2和Beclin 1，促进睾丸增殖（睾丸中增殖细胞核抗原阳性细胞数量增加），恢复睾丸中糖原含量（轻度至中度周期性酸-席夫反应），并保持睾丸结构，从而抑制细胞凋亡和激活自噬。味精对幼年大鼠的睾丸不良反应更为严重，而ALO预处理对成年大鼠的保护作用更强。它在睾丸中的抗炎、抗氧化、抗凋亡、促自噬、抗纤维化和增殖作用表明它在对抗男性生殖功能障碍方面有很大的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.