Ermiş Mustafa, Karakaş Erol, Erol Hanifi, Akcakavak Gökhan, Aci Recai, Ümit Furkan, Karatas Özhan, Çiftci Gülay
Erciyes University Experimental Research Application and Research Center, Kayseri, Turkey.
Op. Dr. Erol Karakaş Clinic, Kayseri, Turkey.
J Mol Histol. 2025 May 19;56(3):159. doi: 10.1007/s10735-025-10448-w.
Cyclophosphamide (CP) is one of the most commonly used chemotherapy agents and carries a high risk of ovarian damage. This study aimed to evaluate the effects of autologous cytokine-rich serum (ACRS) and platelet-rich plasma (PRP) on brain oxidative status, mineral levels, and proinflammatory cytokines in rats with CP-induced ovarian failure. A total of 42 female Wistar rats (12-weeks-old) were used in the study. Six of these rats were allocated as donors, and the remaining 36 rats were randomly distributed into six groups (n = 6 per group). Group 1 received no treatment. On the 1st and 7th days, 75 mg/kg of CP was administered intraperitoneally to Groups 4, 5, and 6. On day 1, PRP was administered intraovarianly to Groups 2 and 5, while ACRS was administered intraovarianly to Groups 3 and 6. Additionally, PRP and ACRS were administered intraperitoneally to the respective groups on 7th and 14th days.The study was terminated at the end of the 31st day. Brain tissue and blood samples were collected for biochemical analyses and ovarian tissue samples were collected for histomorphological examinations. Morphological analysis using Hematoxylin-Eosin (HE) staining and immunohistochemical evaluation for AMH, α-SMA, and IL-1β were conducted on the ovaries. Proinflammatory cytokines and insulin levels were measured using ELISA test kits. TAS/TOS levels were assessed using Relassay Diagnostic kits. Biochemical parameters and mineral levels were measured using autoanalyzer. Histopathological evaluation revealed that follicular degeneration, congestion, hemorrhage, edema, and inflammatory cell infiltration, as well as the number of atretic follicles and IL-1β immunoreactivity, were observed at the highest levels in the CP group (Group 4). In contrast, the numbers of primordial, primary, secondary, and tertiary follicles, along with AMH and α-SMA immunoreactivity levels, were found to be the lowest in this group. However, positive therapeutic effects were observed in the CP-treated groups (Groups 5 and 6). In the serum, increased levels of AST, ALT, creatinine, glucose, LDL, TOS, Ca, Fe, Mg, IL-1β, IL-1α, TNF-α, and NF-kB were detected in the CP groups (G4, G5, G6) compared to the control groups (G1, G2, and G3). In brain tissue, a decrease of total protein and total cholesterol levels were observed in the CP groups (G4, G5, G6) compared to the control groups, while increases in Na, Cl, Fe, IL-1β, IL-1α, TNF-α, and NF-kB levels were detected. In conclusion, PRP and ACRS therapies from the patient's own blood have a potential as supportive or chemopreventive strategies with reduced side effects and treatment costs.
环磷酰胺（CP）是最常用的化疗药物之一，具有较高的卵巢损伤风险。本研究旨在评估自体富细胞因子血清（ACRS）和富血小板血浆（PRP）对CP诱导的卵巢功能衰竭大鼠脑氧化状态、矿物质水平和促炎细胞因子的影响。本研究共使用了42只12周龄的雌性Wistar大鼠。其中6只大鼠被分配为供体，其余36只大鼠随机分为6组（每组n = 6）。第1组不接受任何治疗。在第1天和第7天，向第4、5和6组腹腔注射75 mg/kg的CP。在第1天，向第2组和第5组卵巢内注射PRP，向第3组和第6组卵巢内注射ACRS。此外，在第7天和第14天分别向相应组腹腔注射PRP和ACRS。研究在第31天结束时终止。采集脑组织和血液样本进行生化分析，采集卵巢组织样本进行组织形态学检查。对卵巢进行苏木精-伊红（HE）染色的形态学分析以及对抗苗勒管激素（AMH）、α-平滑肌肌动蛋白（α-SMA）和白细胞介素-1β（IL-1β）进行免疫组化评估。使用酶联免疫吸附测定（ELISA）试剂盒测量促炎细胞因子和胰岛素水平。使用Relassay诊断试剂盒评估总抗氧化状态（TAS）/总氧化状态（TOS）水平。使用自动分析仪测量生化参数和矿物质水平。组织病理学评估显示，在CP组（第4组）中观察到卵泡变性、充血、出血、水肿和炎症细胞浸润，以及闭锁卵泡数量和IL-1β免疫反应性处于最高水平。相比之下，该组中原始卵泡、初级卵泡、次级卵泡和三级卵泡的数量以及AMH和α-SMA免疫反应性水平最低。然而，在CP治疗组（第5组和第6组）中观察到了积极的治疗效果。与对照组（第1、2和3组）相比，CP组（第4、5、6组）血清中天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、肌酐、葡萄糖、低密度脂蛋白（LDL）、TOS、钙（Ca）、铁（Fe）、镁（Mg）、IL-1β、IL-1α、肿瘤坏死因子-α（TNF-α）和核因子-κB（NF-κB）水平升高。在脑组织中，与对照组相比，CP组（第4、5、6组）总蛋白和总胆固醇水平降低，同时钠（Na）、氯（Cl）、铁、IL-1β、IL-1α、TNF-α和NF-κB水平升高。总之，来自患者自身血液的PRP和ACRS疗法有可能作为支持性或化学预防策略，具有减少副作用和治疗成本的潜力。
