Department of Chemistry, College of Science, King Faisal University, Al-Ahsa, Saudi Arabia.
Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt.
Redox Rep. 2022 Dec;27(1):158-166. doi: 10.1080/13510002.2022.2101832.
Methotrexate (MTX) is a commonly used chemotherapeutic drug that has adverse toxic effects on germ cells. Naringin (NG) is a natural flavanone glycoside, with different phytotherapeutic applications, and its possible protective effects against MTX-induced testicular tissue damage were investigated in this study.
Low and high doses of NG (40 and 80 mg/kg/day) were given for 10 days by intraperitoneal (i.p.) injection and MTX (20 mg/kg i.p.) was given at the 4th day of the experiment, with or without NG in rats.
The obtained results showed that exposure to MTX increased malondialdehyde (MDA) levels and nitric oxide (NO) production compared with the control. In the meantime, MTX depleted catalse (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), and reduced glutathione (GSH) in the testicular tissue. Further, serum testosterone levels were significantly decreased in the MTX group. NG significantly counteracted the aforementioned effects of MTX; however, NG80 was more effective in restoring SOD, GR, MDA and NO. Interestingly, NG80 achieved a better improvement in the ultrastructural pattern of the testicular cells in MTX-exposed rats.
These results indicated, for the first time, that NG could be a potential candidate therapy against MTX-reprotoxic impacts.
甲氨蝶呤（MTX）是一种常用的化疗药物，对生殖细胞有不良的毒性作用。柚皮苷（NG）是一种天然类黄酮糖苷，具有不同的植物治疗应用，本研究探讨了其对 MTX 诱导的睾丸组织损伤的可能保护作用。
通过腹腔内（i.p.）注射，连续 10 天给予低剂量和高剂量的 NG（40 和 80mg/kg/天），并在实验的第 4 天给予 MTX（20mg/kg，i.p.），同时给予或不给予 NG。
结果表明，与对照组相比，暴露于 MTX 会增加丙二醛（MDA）水平和一氧化氮（NO）的产生。同时，MTX 耗尽了睾丸组织中的过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、谷胱甘肽还原酶（GR）、谷胱甘肽过氧化物酶（GPx）和还原型谷胱甘肽（GSH）。此外，MTX 组血清睾酮水平显著下降。NG 显著拮抗了 MTX 的上述作用；然而，NG80 在恢复 SOD、GR、MDA 和 NO 方面更有效。有趣的是，NG80 对 MTX 暴露大鼠睾丸细胞的超微结构模式有更好的改善作用。
这些结果首次表明，NG 可能是一种对抗 MTX 生殖毒性影响的潜在候选治疗方法。
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