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

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Ermiş M., Karakaş E., Erol H., Akçakavak G., Aci R., Ümit F., ...Daha Fazla

JOURNAL OF MOLECULAR HISTOLOGY, cilt.59, ss.1-19, 2025 (SCI-Expanded, Scopus)

Özet

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.