Investigating the effects of nicotinamide mononucleotide administration on testicular apoptosis, and mitochondrial function in doxorubicin-treated rats.

چکیده اصلی

BACKGROUND: Male infertility is one of the most important side effects of chemotherapy that can seriously compromise the quality of life of cancer patients. Doxorubicin, a widely used chemotherapy drug in the treatment of cancer patients, is known to cause testicular toxicity. Nicotinamide mononucleotide (NMN) has recently received attention due to its potential role in improving mitochondrial function and cellular resistance to oxidative stress. The aim of the present study was to investigate the protective effects of NMN on testicular apoptosis, inflammatory changes, oxidative stress, and mitochondrial function in rats treated with doxorubicin. MATERIAL AND METHOD: Thirty-two male Wistar rats were randomly assigned into four groups: control, NMN, doxorubicin, and NMN + doxorubicin. NMN (100 mg/kg) was administered intraperitoneally for 28 days, whereas doxorubicin was injected intraperitoneally at a dose of 2 mg/kg every 48 h for 12 days (six injections; cumulative dose 12 mg/kg). Histopathological evaluation was performed using Johnson's scoring system and morphometric analysis of seminiferous tubules. Oxidative stress markers (MDA, SOD, and GPx), intracellular ROS levels, and mitochondrial membrane potential were assessed. In addition, Bax and Bcl-2 gene and protein expression were examined using RT-qPCR and Immunohistochemistry staining. RESULTS: Doxorubicin administration significantly decreased Johnson's score, seminiferous tubule diameter, epithelial thickness, antioxidant enzyme activity, and mitochondrial membrane potential, while markedly increasing ROS levels, lipid peroxidation, and Bax expression (p < 0.05). NMN treatment significantly attenuated these alterations by reducing oxidative stress and apoptosis while improving mitochondrial function and histological architecture of the testes. CONCLUSION: NMN exerts significant protective impact against testicular damages related to doxorubicin via antioxidant, anti-apoptotic, and mitochondrial-protective mechanisms. These findings indicate that NMN attenuates structural and molecular indices of testicular injury induced by doxorubicin, although preservation of endocrine function and fertility potential remains to be established.

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