Do Avanafil and Zaprinast Change Some Selected Cytokine Levels In Ovariectomized Rat’s Liver?

Studies reported that phosphodiesterase-5 inhibitors (PDE-5Is) positively contributed to bone-mineral-density and thickness in rats with ovariectomy, which have the same condition with postmenapozal period. To explain the positive contribution mechanism on bone mineral density of PDE-5Is, we investigated the effect of zaprinast and avanafil on levels of some pro -or anti-resorptive cytokines in ovariectomized-rats. Albino female rats (8 months and 250-350 g) were used and four groups of equal-number were randomly assigned (n=6). Groups; was the sahm operated, positive control (OVX), Zaprinast and OVX, Avanafil and OVX groups, respectively. The levels of Estrogen, IL-1β, IL-6, IL-8, IL-10 and TNF-α were measured by ELISA kits, in liver of rats. IL-1β, IL-6, IL-8 and TNF-α levels were high in groups with OVX compared to sham group, while IL-10 levels were low. Also, IL-1β, IL-6, IL-8 and TNF-α levels were low in zaprinast and especially avanafil-treated groups with OVX and were similar to the sahm group values (p=0.001 for IL-1β, p=0.045 for IL-6, p=0.008 for IL-8, p=0.006 for IL-10, p=0.026 for TNF-α). Zaprinast and especially avanafil inhibited IL-1β, 8 and TNF-α and increased the IL-10 levels compared to the OVX group. This may support opinion that PDE-5Is enhance bone mineralization by inhibiting proresorptive cytokines.

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Eastern Journal of Medicine-Cover
  • ISSN: 1301-0883
  • Başlangıç: 1996
  • Yayıncı: ERBİL KARAMAN
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