PCOS is a reproductive hormonal abnormality and a metabolic disorder. It is frequently associated with insulin resistance, hyperandrogenism, chronic inflammation, and oxidative stress. We aim to investigate the potential therapeutic effects of combined therapy of resveratrol and metformin on polycystic ovaries via SIRT1 and AMPK activation. Wistar albino rats were divided into control and experimental (PCOS) groups. DHEA-induced PCOS rats were given resveratrol (20 mg/kg/day), metformin (300 mg/kg/day) and combined therapy. At the end of the experiment, the body and ovarian weight of rats were measured and blood samples were analyzed for FSH, LH, testosterone, AMH, TNF-α and MDA levels. Histopathological evaluation of ovaries were carried out by light and electron microscopy. SIRT1 and AMPK immunreactivity and TUNEL assay were scored. Data were statistically analyzed by SPSS programme. Metformin and combined treatment groups reduced the body and ovary weights compared to the PCOS group. Serum testosterone levels were significantly higher in the PCOS group than in the control group and this was reduced when PCOS was treated with all but especially resveratrol. All the treatment groups decreased LH, LH/FSH, TNF-α and tissue AMH levels which were induced in the PCOS group, whereas metformin was unable to improve the increased MDA and plasma AMH levels. Treatment with resveratrol and/or metformin ameliorated the elevated number of secondary and atretic follicles and the decreased number of Graafian follicles in the PCOS group, which indicates the effect of the treatments on the maintenance of folliculogenesis. Light and electron microscopic findings supported the analysis of follicular count. Increased number of TUNEL (+) granulosa cells in the PCOS group were reduced significantly in the treatment groups. Resveratrol and metformin increased SIRT1 and AMPK immunreactivity, respectively, compared to the PCOS group. The results suggest that combined therapy of metformin and resveratrol may improve the weight gain, hormone profile and ovarian follicular cell architecture by inducing antioxidant and antiinflammatory systems via SIRT1 and AMPK activation in PCOS.

Background/Aims: Cytokine secretion is known to play an important role in the pathophysiology of depression, and levels of proinflammatory cytokines are increased in chronic renal failure (CRF) patients. The objective of this study was to examine the correlation between levels of proinflammatory cytokines in CRF patients and degree of depression. Methods: 31 patients on hemodialysis, 31 patients on continuous ambulatory peritoneal dialysis, and 31 conservatively managed chronic kidney disease (CKD) patients were enrolled in this study. Depressive symptoms were measured with the Beck Depression Inventory (BDI), and ‘elevated symptoms of depression’ were defined as a BDI score ≧17. IL-6 and TNFα cytokine levels were measured by ELISA. Results: ‘Elevated symptoms of depression’ occurred in 37 of 93 patients (40%). IL-6 and TNFα levels were not significantly different among CRF patients with and without elevated depressive symptoms (p = 0.937 and p = 0.414, respectively). When analyzed by treatment subgroup, proinflammatory cytokine levels were not significantly different in patients with and without elevated symptoms of depression. Conclusion: In patients with CRF, elevated symptoms of depression were not associated with increased cytokine levels.