Abstract
Purpose
Testicular toxicity is one of the most important side effects of cisplatin (CP) therapy. Alpha-pinene (AP) is a naturally occurring monoterpene with antioxidant character in plants. Here, we aimed to evaluate the therapeutic activity of AP against CP-induced testicular toxicity by including the nuclear factor erythroid 2-associated factor 2 (Nrf2) pathway in rats.
Methods
Thirty male rats were divided into 5 groups: control, CP, CP + AP (5 and 10 mg/kg) and only AP (10 mg/kg). CP was administered intraperitoneally at a dose of 5 mg/kg on the first day, followed by three consecutive injections of AP. Serum reproductive hormone levels were evaluated using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers in testicular tissue were also determined colorimetrically. In addition, how CP affects Nrf2 pathway and the effect of AP on this situation were also addressed.
Results
Treatment with CP significantly increased OS, inflammation, ERS and apoptosis in testicular tissue. Administrations of AP resulted in an amelioration of these altered parameters. The mechanism of therapeutic effect of AP appeared to involve induction of Nrf2. Furthermore, these results were also confirmed by histological data.
Conclusion
Results suggest that AP can exhibit therapeutic effects against CP-induced testicular toxicity. It can be concluded that AP may be a potential molecule to abolish reproductive toxicity after chemotherapy.
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Data availability
The data used and analyzed in this article are available from the corresponding author upon reasonable request.
Abbreviations
- 4-HNE:
-
4-hydroxynonenal
- ANOVA:
-
analysis of variance
- AP:
-
alpha-pinene
- ATF6:
-
activating transcription factor 6
- CHOP:
-
CCAAT-enhancer-binding protein homologous protein
- CP:
-
cisplatin
- ELISA:
-
enzyme-linked immunosorbent assay
- ERAD:
-
ER-associated protein degradation
- ERS:
-
endoplasmic reticulum stress
- FSH:
-
follicle-stimulating hormone
- G6PD:
-
glucose-6-phosphate dehydrogenase
- GPx:
-
glutathione peroxidase
- GRP78:
-
glucose-regulated protein 78
- GSH:
-
glutathione
- HMGB1:
-
high mobility group box 1
- HO-1:
-
heme oxygenase-1
- IP:
-
intraperitoneal
- IL-6:
-
interleukin-6
- Keap1:
-
Kelch-ECH-associated protein 1
- LH:
-
luteinizing hormone
- MPO:
-
myeloperoxidase
- NF-κB:
-
nuclear factor kappa B
- Nrf2:
-
nuclear factor erythroid 2-associated factor 2
- NQO-1:
-
NAD(P)H quinone dehydrogenase-1
- OS:
-
oxidative stress
- ROS:
-
reactive oxygen species
- SOD:
-
superoxide dismutase
- TNF-α:
-
tumor necrosis factor-alpha
- UPR:
-
unfolded protein response
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Acknowledgements
The authors wish to thank Sait Al and Ibrahim Aydin from Surgical Practice and Research Center of Karadeniz Technical University (Trabzon, Turkiye) for professional assistance with the experimental studies.
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This study was supported by Office of Scientific Research Projects of Karadeniz Technical University (Project Number: TSA-2023-10656).
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SD, AM and ZTU designed the experiment. SD, AM, ZTU, NTA and EAD performed the experiment. SD, AM and ZTU performed tha data analysis. SD wrote the manuscript. YA revised the manuscript. All authors read and approved the fnal manuscript.
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Demir, S., Mentese, A., Usta, Z.T. et al. Alpha-pinene neutralizes cisplatin-induced reproductive toxicity in male rats through activation of Nrf2 pathway. Int Urol Nephrol 56, 527–537 (2024). https://doi.org/10.1007/s11255-023-03817-5
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DOI: https://doi.org/10.1007/s11255-023-03817-5