article · Pharmaceutics
Chemotherapy using cisplatin frequently leads to ovarian damage and compromised fertility in pre-menopausal cancer patients. This study assessed whether melatonin could act as a protective adjuvant against cisplatin-induced ovarian dysfunction in thirty-two female Wistar rats. Cisplatin administration reduced body and ovarian weights, impaired essential reproductive hormones, depleted antioxidant defences, and caused severe ovarian tissue damage, including damaged follicles and haemorrhage. Molecular analysis revealed increased inflammation, apoptosis, and altered signalling pathways governing cell survival and steroid production. Co-administering melatonin significantly reversed these pathological and hormonal disruptions. Through its antioxidant, anti-inflammatory, and anti-apoptotic actions, melatonin protected ovarian tissue architecture and function, suggesting potential utility in mitigating chemotherapy-associated ovarian toxicity.
Chemotherapy can lead to ovarian failure and infertility in pre-menopausal cancer patients, presenting a serious long-term side effect of cancer treatment. Demonstrating that an accessible compound such as melatonin can mitigate cisplatin toxicity in animal models highlights potential biological pathways for shielding reproductive health during oncological therapies.
This research could inform the development of protective adjuvant therapies for oncology patients receiving cisplatin chemotherapy. Prospective users include clinical oncologists and pharmaceutical companies developing supportive care drugs. Because the evidence is derived entirely from an early-stage study in female rats, the application remains far from clinical use and requires extensive validation through human trials.
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Ovarian damage and fertility impairment are major side effects of chemotherapy in pre-menopausal cancer patients. Cisplatin is a widely used chemotherapeutic drug. The present study was designed to assess the ameliorative effects of melatonin as an adjuvant for fertility preservation. Thirty-two adult female Wistar rats were divided randomly into four equal groups: Control, Melatonin, Cisplatin (CP) treated, and CP + Melatonin treated. The cisplatin-treated group showed decreased body and ovarian weights, decreased serum E2 and AMH, increased serum LH and FSH, reduced ovarian levels of SOD, CAT, GSH, and TAC, and increased ovarian MDA. The histopathological examination of the cisplatin-treated group showed deleterious changes within ovarian tissue in the form of damaged follicles and corpus luteum, hemorrhage, and inflammatory infiltrates with faint PAS reaction in zona pellucida, increased ovarian collagen deposition, and marked expression of caspase-3 immune reaction in granulosa and theca cells, stroma, and oocytes. Alongside, there was a significant downregulation in the mRNA expression of steroidogenic enzymes, IL10, AMPK, PI3K, AKT, mTOR, and PTEN, while TGF-β1, IL1β, IL6, TNF-α, NF-Kβ, P53, p38-MAPK, JNK, and FOXO3 mRNA expressions were upregulated in cisplatin-treated rats' ovarian tissue. Coadministration of cisplatin-treated rats with melatonin reversed these changes significantly. In conclusion, melatonin's antioxidant, anti-inflammatory, and anti-apoptotic activities could modulate ovarian disturbances induced by cisplatin and preserve fertility.
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DOI: 10.3390/pharmaceutics14122769
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