The effect of Nateglinide and Octreotide on follicular morphology and free radical scavenging system in letrazole-induced rat model of PCOS.

OBJECTIVE: To investigate the effects of octreotide and nateglinide on ovarian follicle count, ovarian tissue damage, biochemical parameters and free radical scavenging system in letrazole-induced rat model of PCOS. MATERIALS AND METHODS: Forty-two female Sprague-Dawley rats were divided into six groups. Group 1 (Control Group): after localizing the ovaries and the uterine horns, the abdominal wall was closed without any surgical procedure. Group 2 (PCOS Group): PCOS was induced by administrating Letrozole orally for 21 successive days. At the end of 21 days, rats underwent ovarian biopsies. The experimental PCOS model was considered successful in the presence of atretic follicles without granulosa cell stratification. Group 3 (PCOS + Nateglinide Group): Nateglinide was administered by oral dropper for 30 days to the rats in which PCOS model was created. Group 4 (Nateglinid only Group): 30 days of NG was applied to the rats without PCOS. Group 5 (PCOS+Octreotide Group): 0.1 mg/kg/day Octreotide was given intraperitoneally for 4 weeks to the rats in which PCOS model was created. Group 6 (Octreotide only Group): animals without PCOS given 0.1 mg/kg/day Octreotide at the end of the treatment, bilateral oophorectomy was performed and blood samples were collected from all groups. Ovarian tissue was stained immunohistochemically with TLR-4 in addition to conventional staining. In addition to follicle classification, ovarian damage was graded. Serum insulin, FSH and LH, TNF-α, IL-6, SHBG, SOD, IGF-1, MDA and GSH levels were also measured. RESULTS: The cystic and degenerated follicle density of PCOS group was high compared with the other groups. Both cystic and degenerated follicles were significantly reduced in PCOS+NG and PCOS+OC groups compared to PCOS group. There was no difference between the groups in terms of serum LH, FSH and insulin levels (p>0.05). Serum testosterone level was significantly higher in the PCOS group compared to the other groups (p<0.01). Adding OC or NG to PCOS groups did not cause significant changes in testosterone levels. TNF-α and IL-6 levels were high in PCOS group (p<0.03). IGF-1 and MDA levels were higher in PCOS than in other groups (p<0.03, p<0.01 respectively). Adding OC or NG to the treatment normalized IGF-1 and MDA levels. Serum GSH levels were significantly lower in the PCOS group (p<0.05). Adding NG to the treatment increased GSH levels. CONCLUSIONS: Both NG and OCT reverses atretic and degenerate follicle damage due to PCOS through TLR-4, antioxidant and anti-inflammatory pathways.

Vascular calcification is not related to serum fetuin-A and osteopontin levels in hemodialysis patients.

INTRODUCTION: Vascular calcification (VC) in hemodialysis (HD) patients is a sign of severe cardiovascular disease and can predict cardiovascular outcomes. Fetuin-A and osteopontin (OPN) inhibit VC. Serum fetuin-A levels are lower in patients with end-stage kidney disease (ESKD) and in those who are on chronic HD therapy. However, there are limited data concerning OPN in patients who are on dialysis. The aim of our study was to determine VC in HD patients, the relationship between VC and 25-OH-vitamin D, fetuin-A, and OPN levels, and independent predictors of VC. MATERIALS AND METHODS: Ninety-three patients with ESKD on HD therapy were recruited. Among these patients, 44 were male and 49 were female. The patient group was compared with a group of 20 healthy controls of similar age and sex. A plain radiograph of the hand was taken using a mammography machine for the evaluation of VC. Serum fetuin-A, OPN, and 25-OH-vitamin D levels of both patients and controls were measured. RESULTS: VC was detected in 45 (48.4%) HD patients. When patients were compared with healthy controls, fetuin-A levels (p < 0.029) were significantly lower in patients, whereas OPN (p < 0.000) and VC (p < 0.002) were significantly higher in the patient group. Age [odds ratio (OR) 1.036], the presence of diabetes mellitus (DM) (OR 17.527), and high parathyroid hormone (PTH) levels (OR 1.002) were independent predictors of VC in a logistic regression model including the following factors: age, the presence of DM, HD duration, and serum albumin, phosphate, PTH, 25-OH-vitamin D, fetuin-A, OPN, and calcium levels. No significant correlation was found between patients with VC and patients without VC in terms of fetuin-A, OPN, and 25-OH-vitamin D levels. CONCLUSIONS: VC is a frequent sign in patients undergoing HD and is not related to serum fetuin-A and osteopontin levels. Age, the presence of DM, and high PTH levels were independent predictors of VC in patients undergoing HD. Further studies are warranted to understand the mechanism underlying and the factors contributing to VC.