Department of Comparative and Experimental Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Pathology, Medical Division, National Research Center, Cairo, Egypt.
Biomed Res Int. 2020 Mar 9;2020:2732958. doi: 10.1155/2020/2732958. eCollection 2020.
Tramadol is a centrally acting opioid analgesic that is extensively used. The chronic exposure to tramadol induces oxidative stress and toxicity especially for patients consuming it several times a day. Previously, we and others reported that tramadol induces testicular damage in rats. This study was conducted to investigate the possible protective effect of pomegranate seed extract (PgSE) against tramadol-induced testicular damage in adult and adolescent rats. Male rats were orally treated with tramadol or in a combination with PgSE for three weeks. Testes were then dissected and analyzed. Histological and ultrastructural examinations indicated that tramadol induced many structural changes in the testes of adult and adolescent rats including hemorrhage of blood vessels, intercellular spaces, interstitial vacuoles, exfoliation of germ cells in lumen, cell apoptosis, chromatin degeneration of elongated spermatids, and malformation of sperm axonemes. Interestingly, these abnormalities were not observed in tramadol/PgSE cotreated rats. The morphometric analysis revealed that tramadol disrupted collagen metabolism by elevating testicular levels of collagen fibers but that was protected in tramadol/PgSE cotreatment at both ages. In addition, DNA ploidy revealed that S phase of the cell cycle was diminished when adult and adolescent rats were treated with tramadol. However, the S phase had a normal cell population in the cotreated adult rats, but adolescent rats had a lower population than controls. Furthermore, the phytochemistry of PgSE revealed a high content of total polyphenols and total flavonoids within this extract; besides, the DPPH free radical scavenging activity was high. In conclusion, this study indicated that PgSE has a prophylactic effect against tramadol-induced testicular damage in both adult and adolescent ages, although the tramadol toxicity was higher in adolescent age to be completely protected. This prophylactic effect might be due to the high antioxidant compounds within the pomegranate seeds.
曲马多是一种广泛应用的中枢作用阿片类镇痛药。慢性暴露于曲马多会引起氧化应激和毒性，尤其是对于每天服用多次曲马多的患者。先前，我们和其他人报道曲马多会导致大鼠睾丸损伤。本研究旨在探讨石榴籽提取物（PgSE）对成年和青春期大鼠曲马多诱导的睾丸损伤的可能保护作用。雄性大鼠经口给予曲马多或曲马多联合 PgSE 治疗 3 周。然后将睾丸取出并进行分析。组织学和超微结构检查表明，曲马多诱导成年和青春期大鼠睾丸发生许多结构变化，包括血管、细胞间隙、间质空泡出血，腔中生殖细胞脱落，细胞凋亡，伸长精子细胞染色质变性和精子轴丝畸形。有趣的是，这些异常在曲马多/PgSE 联合治疗的大鼠中未观察到。形态计量学分析表明，曲马多通过升高睾丸胶原纤维水平破坏胶原代谢，但在成年和青春期大鼠的曲马多/PgSE 联合治疗中得到保护。此外，DNA 倍体分析显示，成年和青春期大鼠用曲马多处理时细胞周期 S 期减少。然而，成年大鼠的 S 期有一个正常的细胞群体，而青春期大鼠的细胞群体比对照组少。此外，PgSE 的植物化学分析显示该提取物中总多酚和总类黄酮含量高；此外，DPPH 自由基清除活性高。总之，本研究表明 PgSE 对成年和青春期大鼠的曲马多诱导的睾丸损伤具有预防作用，尽管青春期大鼠的曲马多毒性更高，无法完全保护。这种预防作用可能归因于石榴籽中的高抗氧化化合物。
