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Atorvastatin attenuates testosterone‐induced benign prostatic hyperplasia in rats: role of peroxisome proliferator‐activated receptor‐γ and cyclo‐oxygenase‐2
Author(s) -
Ishola Ismail O.,
Tijani Habeeb K.,
Dosumu Olufunke O.,
Anunobi Charles C.,
Oshodi Tolulope O.
Publication year - 2017
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12301
Subject(s) - pioglitazone , testosterone propionate , testosterone (patch) , endocrinology , atorvastatin , medicine , celecoxib , chemistry , superoxide dismutase , prostate , androgen , oxidative stress , diabetes mellitus , hormone , type 2 diabetes , cancer
Diabetes and obesity have been reported to alter sex steroid hormone metabolism. In this study, an attempt was made to investigate the protective effect of atorvastatin ( ATR ) in combination with celecoxib ( CEL ) or pioglitazone ( PIO ) on testosterone‐induced BPH in rats. Male Wistar rats (200–250 g) were randomly divided into nine groups ( n = 8) and orally treated as follows for 28 consecutive days: group 1: vehicle control (10 mL/kg); group 2: vehicle testosterone (10 mL/kg); groups 3 ‐ 5: ATR (0.5, 2.5, and 5 mg/kg, respectively); group 6: CEL (20 mg/kg); group 7: PIO (20 mg/kg); and groups 8–9: ATR 0.5 mg/kg, and 15 min later, animals were given CEL (20 mg/kg) or PIO (20 mg/kg), respectively. One hour post‐treatment, animals in groups 2–9 were given testosterone propionate (3 mg/kg, s.c.). Twenty‐four hours after last treatment on day 28, blood was collected for serum testosterone and prostate‐specific antigen ( PSA ) analysis. Prostate was harvested for biochemical and histological assays. Subcutaneous injection of testosterone increased serum levels of testosterone and PSA which was ameliorated by pretreatments of rat with ATR , celecoxib, or pioglitazone. Similarly, testosterone‐induced increase in MDA and reduction in the activity of GSH , superoxide dismutase ( SOD ), and catalase were attenuated by ATR . Conversely, celecoxib or pioglitazone treatment failed to affect the activity of antioxidant enzymes. The histology of the prostate showed significant improvement in prostatic cells of ATR , celecoxib, or pioglitazone treated. Findings from the study showed that atorvastatin attenuated testosterone‐induced BPH . Moreover, synergistic effect was observed when atorvastatin was combined with celecoxib.