Department of Addiction, School of Behavioral Sciences and Mental Health (Tehran Institute of Psychiatry), Iran University of Medical Sciences, Tehran, Iran.
Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran; Shiraz Molecular Pathology Research Center, Dr. Daneshbod Pathol Lab, Shiraz, Iran.
Reprod Toxicol. 2023 Sep;120:108453. doi: 10.1016/j.reprotox.2023.108453. Epub 2023 Aug 2.
Methadone (Met) is the most common treatment for opioid addiction. Although Met is effective for treatment of opioid dependence, sexual dysfunctions and infertility have been reported as a major problem in patients under Met treatment. The present study aimed to evaluate the effect of melatonin and N-acetylcysteine (N) on morphine and Met-induced oxidative stress, apoptosis, suppression of blood sexual hormones, impairment in sperm parameters, and sexual dysfunction. Adult male Wistar rats (n = 66) were randomly divided into 11 equal groups (n = 6) as follows: control, sham, morphine, Met, Met+N, Met+ melatonin, Met+melatonin+N, morphine+ Met, morphine+Met+ melatonin, morphine+Met+N, and morphine+Met+ melatonin+N groups. On day 56 post-treatment, the blood was collected from the tail and the serum levels of sex hormones were evaluated, then the rats were sacrificed, and their bilateral testes and epididymis were retrieved for histological, immunohistochemical, molecular, testicular tissue stress oxidative status, and sperm parameters assays. Exposure to morphine, Met, and shift of morphine to Met resulted in testicular degeneration that can be attributed to generating the stress oxidative-induced- apoptotic testicular cell death and impairing spermatogenesis. Melatonin and N alone and particularly, in combination with each other improved testicular degeneration, sex hormone suppression, and testicular function mediated by increasing the testicular antioxidant capacity and inhibition of the apoptosis pathway. It's suggested that oral administration of antioxidants may be an effective treatment for attenuating some opioid-related testicular dysfunction and degeneration.
美沙酮（Met）是治疗阿片类药物成瘾最常用的方法。虽然 Met 对治疗阿片类药物依赖有效，但有报道称，性性功能障碍和不孕是接受 Met 治疗的患者的主要问题。本研究旨在评估褪黑素和 N-乙酰半胱氨酸（N）对吗啡和 Met 诱导的氧化应激、细胞凋亡、抑制血液性激素、精子参数损伤和性功能障碍的影响。成年雄性 Wistar 大鼠（n=66）随机分为 11 组（n=6）：对照组、假手术组、吗啡组、Met 组、Met+N 组、Met+褪黑素组、Met+褪黑素+N 组、吗啡+Met 组、吗啡+Met+褪黑素组、吗啡+Met+N 组和吗啡+Met+褪黑素+N 组。在治疗后第 56 天，从尾部采集血液并评估血清性激素水平，然后处死大鼠，取出其双侧睾丸和附睾进行组织学、免疫组织化学、分子、睾丸组织应激氧化状态和精子参数检测。暴露于吗啡、Met 和将吗啡转移到 Met 会导致睾丸退化，这可归因于产生应激氧化诱导的凋亡性睾丸细胞死亡并损害生精作用。褪黑素和 N 单独使用，特别是联合使用，通过增加睾丸抗氧化能力和抑制凋亡途径，改善了睾丸退化、抑制性激素和睾丸功能。提示口服抗氧化剂可能是减轻一些阿片类药物相关睾丸功能障碍和退化的有效治疗方法。
