Protective effects of crocin against gentamicin-induced damage in rat testicular tissue: Modulating the levels of NF-κB/TLR-4 and Bax/Bcl-2/caspase-3 signaling pathways

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology Pub Date : 2025-03-22 DOI:10.1016/j.fct.2025.115407

Tuba Dogan , Betul Apaydın Yıldırım , Kubra Asena Terim Kapakin , Metin Kiliçliogli , Esra Aktas Senocak

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Abstract

This study investigated the protective effects of crocin (CRO) on gentamicin (GM)-induced testicular toxicity in adult rats, focusing on oxidative stress, apoptosis, and inflammatory pathways such as Nuclear Factor Kappa B (NF-κB)/Toll-Like Receptor 4 (TLR-4) and Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2)/Caspase-3. Thirty-six male Sprague Dawley rats were divided into six groups: saline only, 25 mg/kg CRO, 50 mg/kg CRO, 80 mg/kg GM, 80 mg/kg GM + 25 mg/kg CRO, 80 mg/kg GM + 50 mg/kg CRO. Treatments were administered intraperitoneally for 8 days. GM increased malondialdehyde (MDA) levels, ischemia-modified albumin (IMA) levels and reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in testicular tissue, indicating oxidative stress. Histopathology showed testicular degeneration. It also elevated Bax, Caspase-3, NF-κB, and TLR-4 expression while decreasing Bcl-2 levels, promoting apoptosis and inflammation. CRO treatment counteracted these effects by enhancing antioxidant enzyme activity, restoring GSH levels, and reducing MDA. Furthermore, CRO exhibited antiapoptotic and anti-inflammatory properties by modulating Bax/Bcl-2 and Caspase-3, and downregulating NF-κB/TLR-4 pathways. This study underscores crocin's protective effects against gentamicin-induced testicular toxicity through the modulation of key signaling pathways, suggesting its potential as a therapeutic strategy for aminoglycoside-induced reproductive damage.

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藏红花素对庆大霉素诱导的大鼠睾丸组织损伤的保护作用：调节NF-κB/TLR-4和Bax/Bcl-2/Caspase-3信号通路的水平

本研究探讨了西红花素（CRO）对庆大霉素（GM）诱导的成年大鼠睾丸毒性的保护作用，重点关注氧化应激、细胞凋亡和炎症途径，如核因子κB (NF-κB)/ toll样受体4 （TLR-4）和Bcl-2相关X蛋白(Bax)/ B细胞淋巴瘤2 (Bcl-2)/Caspase-3。将36只雄性Sprague Dawley大鼠分为单纯生理盐水、25 mg/kg CRO、50 mg/kg CRO、80 mg/kg GM、80 mg/kg GM + 25 mg/kg CRO、80 mg/kg GM + 50 mg/kg CRO 6组。腹腔注射治疗8天。转基因提高睾丸组织丙二醛（MDA）、缺血修饰白蛋白（IMA）水平，降低谷胱甘肽（GSH）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）活性，提示氧化应激。组织病理学显示睾丸变性。上调Bax、Caspase-3、NF-κB、TLR-4表达，降低Bcl-2水平，促进细胞凋亡和炎症反应。CRO处理通过增强抗氧化酶活性、恢复GSH水平和降低MDA来抵消这些影响。此外，CRO通过调节Bax/Bcl-2和Caspase-3，下调NF-κB/TLR-4通路，具有抗凋亡和抗炎作用。本研究强调了藏红花素通过调节关键信号通路对庆大霉素诱导的睾丸毒性的保护作用，提示其作为氨基糖苷诱导的生殖损伤的治疗策略的潜力。

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来源期刊

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.