Arunachalam Seenipandi, Nagoor Meeran Mohamed Fizur, Azimullah Sheikh, Kumar Jha Niraj, Saraswathiamma Dhanya, Albawardi Alia, Beiram Rami, Ojha Shreesh
Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates.
Department of Biotechnology, School of Engineering and Technology (SET), Sharda University, Greater Noida 201310, Uttar Pradesh, India.
Nutrients. 2022 Nov 3;14(21):4648. doi: 10.3390/nu14214648.
The present study investigated the effects of α-bisabolol on DOX-induced testicular damage in rats. Testicular damage was induced in rats by injecting DOX (12.5 mg/kg, i.p., single dose) into rats. α-Bisabolol (25 mg/kg, i.p.) was administered to the rats along with DOX pre- and co-treatment daily for a period of 5 days. DOX-injected rats showed a decrease in absolute testicular weight and relative testicular weight ratio along with concomitant changes in the levels/expression levels of oxidative stress markers and Nrf2 expression levels in the testis. DOX injection also triggered the activation of NF-κB/MAPK signaling and increased levels/expression levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and inflammatory mediators (iNOS and COX-2) in the testis. DOX triggered apoptosis, manifested by an increment in the expression levels of pro-apoptotic markers (Bax, Bcl2, cleaved caspase-3 and -9, and cytochrome-C) and a decline in the expression levels of anti-apoptotic markers (Bcl-xL and Bcl2) in the testis. Additionally, light microscopy revealed the changes in testicular architecture. α-Bisabolol rescued alterations in the testicular weight; restored all biochemical markers; modulated the expression levels of Nrf2-mediated antioxidant responses, NF-κB/MAPK signaling, endoplasmic reticulum (ER) stress, and apoptosis markers in DOX-injected testicular toxicity in rats. Based on our findings, it can be concluded that α-bisabolol has the potential to attenuate DOX-induced testicular injury by modifying NF-κB/MAPK signaling and the ER-stress-mediated mitochondrial pathway of apoptosis by invoking Nrf2-dependent antioxidant defense systems in rats. Based on the findings of the present study, α-bisabolol could be suggested for use as an agent or adjuvant with chemotherapeutic drugs to attenuate their deleterious effects of DOX on many organs including the testis. However, further regulatory toxicology and preclinical studies are necessary before making recommendations in clinical tests.
本研究调查了α-红没药醇对阿霉素诱导的大鼠睾丸损伤的影响。通过向大鼠腹腔注射阿霉素（12.5mg/kg，单次剂量）诱导大鼠睾丸损伤。α-红没药醇（25mg/kg，腹腔注射）在阿霉素预处理和联合治疗期间每天给予大鼠，持续5天。注射阿霉素的大鼠睾丸绝对重量和相对睾丸重量比降低，同时睾丸中氧化应激标志物水平/表达水平和Nrf2表达水平发生相应变化。阿霉素注射还触发了NF-κB/MAPK信号通路的激活，并增加了睾丸中促炎细胞因子（TNF-α、IL-6和IL-1β）和炎症介质（iNOS和COX-2）的水平/表达水平。阿霉素引发了细胞凋亡，表现为睾丸中促凋亡标志物（Bax、Bcl2、裂解的caspase-3和-9以及细胞色素-C）表达水平的增加和抗凋亡标志物（Bcl-xL和Bcl2）表达水平的下降。此外，光学显微镜检查揭示了睾丸结构的变化。α-红没药醇挽救了睾丸重量的改变；恢复了所有生化标志物；调节了Nrf2介导的抗氧化反应、NF-κB/MAPK信号通路、内质网（ER）应激和凋亡标志物在注射阿霉素的大鼠睾丸毒性中的表达水平。基于我们的研究结果，可以得出结论，α-红没药醇有可能通过调节NF-κB/MAPK信号通路和内质网应激介导的线粒体凋亡途径，在大鼠中激活Nrf2依赖性抗氧化防御系统，从而减轻阿霉素诱导的睾丸损伤。基于本研究的结果，α-红没药醇可被建议用作一种药物或与化疗药物联合使用，以减轻阿霉素对包括睾丸在内的许多器官的有害影响。然而，在临床测试中提出建议之前，还需要进一步的监管毒理学和临床前研究。
