Faculty of Medicine, Department of Medical Pharmacology, Bilecik Şeyh Edebali University, Bilecik 11230, Turkey.
Faculty of Medicine, Department of Physiology, Erzincan Binali Yildirim University, Erzincan 24100, Turkey.
Reprod Toxicol. 2024 Aug;127:108611. doi: 10.1016/j.reprotox.2024.108611. Epub 2024 May 21.
The current study aimed to investigate the sensitivity of male testis parenchyma cells to chemotherapy agents and the protective effects and mechanisms of Morinda citrifolia (Noni) administration against structural and functional changes before and after chemotherapy (Paclitaxel (PTX)). For this purpose, rats were randomly assigned into four groups (Control = G1, PTX 5 mg/kg = G2; PTX + Noni 10 mg/kg = G3, PTX + Noni 20 mg/kg = G4). PTX was injected intraperitoneally for 4 consecutive weeks, at a dose of 5 mg/kg to all groups except the control group. Then noni was administrated in 10 (G3) and 20 (G4) mg/kg groups orally (gavage) for 14 days. Biochemical analyses, Real-Time Polymerase Chain Reaction (PCR), and immunohistochemical analyses were performed. According to our results, Total Oxidative Stress (TOS) and Malondialdehyde (MDA) were significantly increased in the PTX group (P < 0.01). Superoxide Dismutase (SOD) enzyme activity and Total Antioxidant Capacity (TAC) levels were decreased (P < 0.01). The changes in the rats treated with PTX + Noni 20 mg/kg were noteworthy. The increased levels of IL1-β (Interleukin 1 beta) and TNFα (tumor necrosis factor-alpha) with PTX were down-regulated after treatment with PTX + Noni 20 mg/kg (P < 0.01) (9 % and 5 % respectively). In addition, Noni restored the testicular histopathological structure by reducing caspase-3 expression and significantly (61 %) suppressed oxidative DNA damage and apoptosis (by regulating the Bax (bcl-2-like protein 4)/Bcl-2 (B-cell lymphoma gene-2) ratio). In conclusion, Noni reduced cellular apoptosis and drastically changed Caspase 8 and Bax/Bcl-2 levels. Furthermore, it considerably decreases oxidative damage and can be used in testicular degeneration.
本研究旨在探讨化疗药物对雄性睾丸实质细胞的敏感性,以及在化疗(紫杉醇(PTX))前后,诺丽(Morinda citrifolia)对结构和功能变化的保护作用及其机制。为此,将大鼠随机分为四组(对照组=G1、PTX 5mg/kg=G2;PTX+诺丽 10mg/kg=G3、PTX+诺丽 20mg/kg=G4)。除对照组外,所有组均连续 4 周每周腹腔注射 PTX 5mg/kg,然后在 G3 和 G4 组分别以 10(G3)和 20(G4)mg/kg 的剂量经口(灌胃)给予诺丽 14 天。进行了生化分析、实时聚合酶链反应(PCR)和免疫组织化学分析。根据我们的结果,PTX 组总氧化应激(TOS)和丙二醛(MDA)显著增加(P<0.01)。超氧化物歧化酶(SOD)酶活性和总抗氧化能力(TAC)水平降低(P<0.01)。PTX+诺丽 20mg/kg 治疗的大鼠变化值得注意。PTX 引起的 IL1-β(白细胞介素 1 beta)和 TNFα(肿瘤坏死因子-α)水平升高在用 PTX+诺丽 20mg/kg 治疗后下调(P<0.01)(分别为 9%和 5%)。此外,诺丽通过降低 caspase-3 表达,通过调节 Bax(bcl-2 样蛋白 4)/Bcl-2(B 细胞淋巴瘤基因-2)比值,减轻了睾丸组织病理学结构的损伤,并显著抑制了氧化 DNA 损伤和细胞凋亡(61%)。总之,诺丽减少了细胞凋亡,并大大改变了 Caspase 8 和 Bax/Bcl-2 水平。此外,它可显著减少氧化损伤,并可用于睾丸退化。