Department of Medical Physiology, Faculty of Medicine, Tanta University, Tanta, Egypt.
Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt.
Redox Rep. 2022 Dec;27(1):177-185. doi: 10.1080/13510002.2022.2116551.
This study aimed to evaluate the potential mitigating effect of fisetin on monosodium glutamate (MSG)-induced testicular toxicity and investigate the possible involvement of silent mating type information regulation 2 homolog 1 (SIRT1) in this effect.
Forty male rats were divided into normal control, fisetin-treated, MSG-treated, and fisetin + MSG-treated groups. Testosterone, GnRH, FSH, and LH were measured in plasma, as well as SIRT1 and phosphorylated AMP-activated protein kinase (pAMPK) levels in testicular tissues using ELISA. Hydrogen peroxide (HO), nitric oxide (NO), and reduced glutathione (GSH) were measured colorimetrically, while expression was relatively quantified using RT-PCR in testicular tissues.
After 30 days, fisetin could ameliorate MSG-induced testicular toxicity by acting centrally on the hypothalamic-pituitary-gonadal axis, increasing plasma levels of GnRH, FSH, LH, and testosterone. Peripheral actions of fisetin on the testis were indicated as it increased testicular SIRT1 and pAMPK. Furthermore, it antagonized glutamate-induced oxidative stress by significantly lowering HO, NO, and relative expression while significantly increasing reduced GSH levels. It also improved the architecture of the seminiferous tubules, reduced sperm abnormality, and increased sperm count.
Fisetin ameliorates MSG-induced testicular toxicity via central and peripheral mechanisms making it a promising therapeutic target for male infertility.
本研究旨在评估非瑟酮对谷氨酸单钠（MSG）诱导的睾丸毒性的潜在缓解作用，并探讨沉默交配型信息调节 2 同源物 1（SIRT1）在此作用中的可能参与。
将 40 只雄性大鼠分为正常对照组、非瑟酮处理组、MSG 处理组和非瑟酮+MSG 处理组。使用 ELISA 法测量血浆中的睾酮、促性腺激素释放激素（GnRH）、卵泡刺激素（FSH）和黄体生成素（LH），以及睾丸组织中的 SIRT1 和磷酸化 AMP 激活蛋白激酶（pAMPK）水平。使用比色法测量睾丸组织中的过氧化氢（HO）、一氧化氮（NO）和还原型谷胱甘肽（GSH），并使用 RT-PCR 相对定量 表达。
30 天后，非瑟酮通过对下丘脑-垂体-性腺轴的中枢作用，增加 GnRH、FSH、LH 和睾酮的血浆水平，从而改善 MSG 诱导的睾丸毒性。非瑟酮对睾丸的外周作用表现为增加睾丸 SIRT1 和 pAMPK。此外，它通过显著降低 HO、NO 和相对 表达，同时显著增加还原型 GSH 水平来拮抗谷氨酸诱导的氧化应激。它还改善了曲细精管的结构，减少了精子异常，增加了精子计数。
非瑟酮通过中枢和外周机制改善 MSG 诱导的睾丸毒性，使其成为男性不育症有希望的治疗靶点。
