In:
Fundamental & Clinical Pharmacology, Wiley, Vol. 29, No. 3 ( 2015-06), p. 286-298
Abstract:
Cyclophosphamide ( CYP ) is a chemotherapeutic agent with a potent ovarian toxic effect. CYP induces granulosa cell apoptosis and oxidative stress. Irbesartan ( IRB ) is a unique ARB with a peroxisome proliferator‐activated receptor‐gamma ( PPAR ‐γ) agonistic activity. As PPAR ‐ɣ activation exerts anti‐inflammatory effects and reduces ROS production, IRB may further reduce inflammatory chemokine expression and suppress apoptotic cell death. Therefore, this study aimed to evaluate the effects of IRB on the development of CYP ‐induced ovarian damage. Rats were divided into four groups: control group, IRB group (100 mg/kg, orally), CYP group (100 mg/kg, i.p . single injection), and IRB + CYP group ( IRB administered 9 days before and 6 days after CYP administration). Rats sacrificed on day 16 of experiment; estradiol ( E 2), FSH , and TNF ‐α levels were estimated in serum. Reduced glutathione ( GSH ), malondialdehyde ( MDA ), superoxide dismutase ( SOD ) and caspase‐3 activities, myeloperoxidase ( MPO ), and IL ‐10 levels were determined in ovarian tissues. Protein expressions of p53, caspase‐3, K i‐67, and R ad‐51 were estimated by immunohistochemical and Western blot techniques. CYP produced ovarian damage as indicated from the decline in serum E 2; elevation in FSH ; unbalance in tissue oxidative stress parameters; increase in MPO , TNF ‐α levels, caspase‐3 activity/expression, p53, and R ad‐51 expression; and decrease in IL ‐10 contents, without effect on K i‐67. On the other hand, IRB , significantly reduced the toxic effects of CYP as indicted from normalization of E 2, FSH , oxidative stress, apoptotic, and inflammatory mediators. These data were further supported by histopathological studies. Thus, co‐administration of IRB may be promising in alleviating the ovarian toxic effects of CYP .
Type of Medium:
Online Resource
ISSN:
0767-3981
,
1472-8206
DOI:
10.1111/fcp.2015.29.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2006242-4
SSG:
15,3
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