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