In this study, the potential effects of hesperidin (HES) on chronic toxicity caused by abamectin (ABM) in the testicular tissue were investigated through oxidative stress, inflammation, endoplasmic reticulum stress (ERS), apoptosis, and autophagy pathways. Male Sprague Dawley rats were used in the study. Animals in the ABM group were orally administered 1 mg/kg ABM every other day for 28 days, while HES used against ABM was given at 100 or 200 mg/kg 30 min after ABM administration for 28 days. Markers of oxidative stress, inflammation, ERS, apoptosis, and autophagy in the testicular tissues removed after the animals are sacrificed were analyzed using biochemical, real-time polymerase chain reaction (RT-PCR), or western blot techniques. The results obtained showed that ABM caused oxidative stress, and triggered ERS, inflammation, apoptosis, and autophagy. On the other hand, HES showed antioxidant effect by increasing superoxide dismutase, catalase, glutathione peroxidase enzyme activities, and glutathione levels in testis tissue and attenuated lipid peroxidation. Accordingly, MAPK14 reduced the NF-κB, IL-1β, TNF-α, and IL-6 expression levels, presenting an anti-inflammatory effect. In addition, Bax protected against apoptosis and autophagy by reducing the caspase-3, beclin-1, LC3A, and LC3B expressions, and increasing Bcl-2 expression. It was observed that HES also interrupted the JAK2/STAT3 signaling pathway by suppressing IL-6 expression. Taken into consideration together, HES provided significant protection against the destruction caused by ABM in testicular tissue with antioxidant, anti-inflammatory, antiapoptotic, and anti-autophagic effects. Thus, it was revealed that HES has the potential to serve as an alternative treatment option in ABM toxicity.

中文翻译：

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研究橙皮苷通过氧化应激、内质网应激、炎症、细胞凋亡、自噬和 JAK2/STAT3 通路对阿维菌素诱导的大鼠睾丸毒性的影响

本研究通过氧化应激、炎症、内质网应激（ERS）、细胞凋亡和自噬途径研究橙皮苷（HES）对睾丸组织中阿维菌素（ABM）引起的慢性毒性的潜在影响。研究中使用雄性 Sprague Dawley 大鼠。ABM 组动物每隔一天口服 1 mg/kg ABM，持续 28 天，而用于对抗 ABM 的 HES 在 ABM 给药后 30 分钟以 100 或 200 mg/kg 给药，持续 28 天。使用生化、实时聚合酶链反应 (RT-PCR) 或蛋白质印迹技术分析在动物被处死后取出的睾丸组织中的氧化应激、炎症、ERS、细胞凋亡和自噬的标志物。结果表明，ABM 引起氧化应激，并引发 ERS、炎症、细胞凋亡、和自噬。另一方面，HES 通过增加睾丸组织中的超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶活性和谷胱甘肽水平以及减弱脂质过氧化来显示抗氧化作用。因此，MAPK14 降低了 NF-κB、IL-1β、TNF-α 和 IL-6 的表达水平，呈现出抗炎作用。此外，Bax 通过降低 caspase-3、beclin-1、LC3A 和 LC3B 的表达并增加 Bcl-2 的表达来防止细胞凋亡和自噬。据观察，HES 还通过抑制 IL-6 表达来中断 JAK2/STAT3 信号通路。综合考虑，HES 对睾丸组织中 ABM 造成的破坏具有显着的保护作用，具有抗氧化、抗炎、抗凋亡和抗自噬作用。因此，