COMBINATION OF RESVERATROL WITH VITAMIN D AMELIORATES HEPATIC TISSUE DAMAGES, OXIDATIVE/ER STRESSES AND INFLAMMATION IN HIGHFRUCTOSE/LOW-STREPTOZOTOCIN INDUCED DIABETIC RATS


Dağıstanlı F., Aykaç M., Uysal Ö., Tanrıverdi G., Ulusu N., Ulutin A. N. T., ...Daha Fazla

ICSD2022"Future of Cell Death in Basic Science and Translational Medicine", İstanbul, Türkiye, 2 - 04 Temmuz 2022, ss.75, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: İstanbul
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.75
  • İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet

Özet

A high-fructose diet is considered as one of the major causes of diabetes and liver disorders.In this study, we investigated the effects of combined resveratrol (RES) and vitamin D (VitD) treatment on the oxidative and endoplasmic reticulum (ER) stresses, inflammation, apoptosis, and liver regeneration in a Type 2 diabetes mellitus (T2DM) animal model. The T2DM model was created by a combination of 10% fructose-diet and streptozotocin (STZ, 40mg/kg) in rats. RES (1mg/kg/day) and VitD (170/IU/week) were administered alone or combined to the diabetic and control groups. Blood glucose (BG), serum insulin (INS) and GLP-1 levels, the cellular oxidative stress status (G6PD, 6-PGD, GR and GST activities) were measured. GRP78, NF-κB, TNF-α, IL-6, IL-1β, caspase-3 and PCNA antibodies were used for immunohistochemical staining. TUNEL method, semithin section-toluidin blue and Sirius red staining were used to determine the apoptosis, fatty degeneration and fibrosis, respectively. We observed that BG levels and serum INS levels were increased, while GLP-1 were decreased in the diabetic group compared with the control groups. The expression of cytokines (IL-1β, IL-6 and TNF-α) in parallel with NF-κB activation significantly increased in the diabetic group (p<0.001). Increased GRP78 expression indicating ER stress, enhanced caspase-3 activation and increased number of apoptotic cells, increased lipid storage in hepatocytes and collagen accumulation surrounding the central vein were observed in the diabetic group. The combination of RES and VitD treatment improved the antioxidant defense via increasing G6PD, 6-PGD, GR and GST activtiy, also the INS levels were similar to the control group. We found that the combined treatment of RES with VitD prevents the adverse effects of T2DM by regulating BG, GLP-1 and insulin levels, increasing anti-oxidant defense, triggering tissue regeneration, improving inflammation and ER stress, reducing apoptosis in the liver cells. This study indicates that combined treatment of RES with VitD might be a beneficial option for the prevention of liver damages in high fructose-induced diabetes.