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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.

Background: Acrylamide is toxic both in experimental animals and in humans. It is proved to be carcinogenic in rodents and considered by The International Agency for Research on Cancer as a probable human carcinogen. Medicinal plants have significant antioxidant properties. Ginger had the highest antioxidant activity among these plants. Aim of the work:To detect the histopathological effects of acrylamide on the kidneys in postnatal rats and to determine the possible protective effect of Ginger (Zingiber officinale Roscoe) as an antioxidant. Methods: The experimental pregnant rats were randomly divided into 3 groups: Group 1 (control group): these rats were preserved under normal condition of diet and water. Group 2 (acrylamide-treated group): acrylamide was orally administered to non-anesthetized rats by gastric intubation at a dose of 10 mg/kg/day. Group 3 (ginger-protected group): animals of this group were given the same dose of acrylamide as in group 2 followed by 1 ml of final aqueous extract of ginger (24 mg/ml) three times weekly. All the doses were administered from the 7th day of gestation and continued up to 21 days after delivery. Postnatal rats at the 2nd and 21st days were selected from each group and were scarified. Their kidneys were carefully dissected, removed and fixed in 10% formalin for histopathological and immunohistochemical examinations. Results: Maternal acrylamide administration disturbed the development of the renal cortex of the offsprings. Histological examination of acrylamide-treated, 2-day-old rats revealed degenerated glomeruli with lack of capillary tufts, disarrangement of podocytes and thickening of the parietal layers of Bowman's capsules. Moreover, the damage was evident in the primitive tubules. Examination of acrylamide-treated, 21-day-old rats showed congested glomerular capillaries, mesangial hypercellularity, vacuolations and darkly stained nuclei of the renal tubular epithelium, and extensive interstitial cellular infiltration and hemorrhage. Statistically, acrylamide-treated groups at both ages showed a highly significant decrease in the mean glomerular count, and the mean thickness of the cortex and the medulla as compared to their control groups. Moreover, the area percentage of renal NF-kβ protein expression showed a significant increase with acrylamide treatment. Ginger administration effectively restored most of the acrylamide-induced renal cortical damage. Conclusion: ginger administration effectively restored most of the acrylamide-induced renal cortical damage, suggesting that ginger supplement can play a protective role against acrylamide deleterious effects.

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