title: Protective effect of mirtazapine and hesperidin on cyclophosphamide-induced oxidative damage and infertility in rat ovaries.
abstract: Cyclophosphamide (CP) causes infertility due to ovarian toxicity. The toxicity mechanism suggests oxidative stress. We assessed whether mirtazapine (MTZ) and hesperidin (HSP) could promote ovarian protection against damage due to CP chemotherapy. Female Wistar rats aged 14 weeks were used. Animals were divided into four groups: control vehicle group (n = 8); CP group (n = 8, rats received 150 mg/kg of CP, single intraperitoneal [i.p.] injection); CP + MTZ group (n = 8, rats received same dose of CP + 30 mg/kg of MTZ, orally, daily); and HSP + CP group (n = 8, rats received same dose of CP + 100 mg/kg of HSP, orally, daily). After eight days of medication, ovaries were removed and ovarian toxicity was assessed by counting follicles and corpora lutea. Nitric oxide (NO) and malondialdehyde (MDA) levels, myeloperoxidase (MPO), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities were estimated in ovarian tissue. NO level, MDA level, and MPO activity were increased (P < 0.001), while, GPx and SOD activities were lowered significantly (P < 0.001) in CP-treated group compared with control vehicle. In addition, ovulation, number of follicles, and ovarian weight were reduced by CP treatment. On the contrary, rats pretreated with MTZ and HSP showed significant decrease in NO, MDA levels, and MPO activity, while, activities of SOD and GPx were increased (P < 0.001). Oxidative stress induced by CP in the rat ovary causes infertility in the female rats. HSP and MTZ could reverse this effect and provide protection of fertility against CP-induced toxicity.
authors: Department of Biochemistry, Faculty of Pharmacy, Tanta University, 31527 Tanta, Egypt naglaa_khedr2000@yahoo.com.
authors: Naglaa Fathi
authors: NF
authors: Khedr
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000633:toxicity*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006569:Hesperidin / Q000494:pharmacology* / Q000627:therapeutic use; D007247:Infertility, Female / Q000139:chemically induced* / Q000517:prevention & control; D008315:Malondialdehyde / Q000032:analysis; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000078785:Mirtazapine; D009569:Nitric Oxide / Q000032:analysis; D010053:Ovary / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000975:Antioxidants; D008803:Mianserin; D009569:Nitric Oxide; D008315:Malondialdehyde; D003520:Cyclophosphamide; D000078785:Mirtazapine; D006569:Hesperidin; D009195:Peroxidase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: Cyclophoshamide; fertility; hesperidin; mirtazapine; oxidative stress