Ijaz Muhammad Umar, Ishtiaq Ayesha, Tahir Arfa, Alvi Mughees Aizaz, Rafique Azhar, Wang Peng, Zhu Guo-Ping
Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad, Pakistan.
Anhui Provincial Key Laboratory of Molecular Enzymology and Mechanism of Major Diseases, Auhui Provincial Engineering Research Centre for Molecular Detection and Diagnostics, College of Life Sciences, Anhui Normal University, Wuhu, Anhui, China.
Toxicol Appl Pharmacol. 2023 Dec 15;481:116750. doi: 10.1016/j.taap.2023.116750. Epub 2023 Nov 18.
Aflatoxin B (AFB) is the most hazardous aflatoxin that causes significant damage to the male reproductive system. Genkwanin (GNK) is a bioactive flavonoid that shows antioxidant and anti-inflammatory potential. Therefore, the current study was planned to evaluate the effects of GNK against AFB-induced testicular toxicity. Forty-eight male rats were distributed into four groups (n = 12 rats). AFB (50 μg/kg) and GNK (20 mg/kg) were administered to the rats for eight weeks. Results of the current study revealed that AFB exposure induced adverse effects on the Nrf2/Keap1 pathway and reduced the expressions and activities of antioxidant enzymes. Additionally, it increased the levels of oxidative stress markers. Furthermore, expressions of steroidogenic enzymes were down-regulated by AFB intoxication. Besides, AFB exposure reduced the levels of gonadotropins and plasma testosterone, which subsequently reduced the epididymal sperm count, motility, and hypo-osmotic swelled (HOS) sperms, while increasing the number of dead sperms and causing morphological anomalies of the head, midpiece, and tail of the sperms. In addition, AFB decreased the activities of testicular function marker enzymes and the levels of inflammatory markers. Moreover, it severely affected the apoptotic profile by up-regulating the expressions of Bax and Casp3, while down-regulating the Bcl2 expression. Besides, AFB significantly damaged the histoarchitecture of testicular tissues. However, GNK treatment reversed all the AFB-induced damages in the rats. Taken together, the current study reports the potential use of GNK as a therapeutic agent to prevent AFB-induced testicular toxicity due to its antioxidant, anti-inflammatory, and anti-apoptotic properties.
黄曲霉毒素B(AFB)是最具危害性的黄曲霉毒素,会对雄性生殖系统造成严重损害。芫花素(GNK)是一种具有生物活性的黄酮类化合物,具有抗氧化和抗炎潜力。因此,本研究旨在评估GNK对AFB诱导的睾丸毒性的影响。将48只雄性大鼠分为四组(每组n = 12只大鼠)。给大鼠分别施用AFB(50μg/kg)和GNK(20mg/kg),持续八周。本研究结果显示,暴露于AFB会对Nrf2/Keap1信号通路产生不利影响,并降低抗氧化酶的表达和活性。此外,它还会增加氧化应激标志物的水平。此外,AFB中毒会下调类固醇生成酶的表达。此外,暴露于AFB会降低促性腺激素和血浆睾酮的水平,进而减少附睾精子数量、活力和低渗肿胀(HOS)精子数量,同时增加死精数量,并导致精子头部、中段和尾部出现形态异常。此外,AFB会降低睾丸功能标记酶的活性和炎症标志物的水平。此外,它通过上调Bax和Casp3的表达,同时下调Bcl2的表达,严重影响细胞凋亡情况。此外,AFB会显著破坏睾丸组织的组织结构。然而,GNK治疗逆转了大鼠中所有由AFB诱导的损伤。综上所述,本研究报告了GNK因其抗氧化、抗炎和抗凋亡特性,具有作为治疗剂预防AFB诱导的睾丸毒性的潜在用途。