Effect of Autologous Cytokine-Rich Serum and Platelet-Rich Plasma Administration on Oxidative Status, Minerals and Proinflammatory Cytokines in Brain and Serum in Cyclophosphamide-Induced Ovarian Failure

Abstract

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, alpha-SMA, and IL-1 beta 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-1 beta 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 alpha-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-1 beta, IL-1 alpha, TNF-alpha, 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-1 beta, IL-1 alpha, TNF-alpha, 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.