The effects of resveratrol on liver damage and ferroptosis in fructose and streptozotocin-induced diabetic model

In this study, a modified Type 2 diabetes model was created by applying low-dose streptozotocin with high fructose, and the effects of resveratrol treatment on possible liver damage and ferroptosis were investigated. 4 Experimental groups were formed. Diabetic group(F), Diabetic group with resveratrol treatment(FR), Control group with resveratrol treatment(KR), Control group(K). At the end of the experiment, all animals were sacrificed and their livers were removed. During the experiment, blood sugar and body weights were measured. For morphological evaluation, Hematoxylin-Eosin, Prussian Blue, Van Gieson and immunohistochemical staining of SIRT1, COX2, HO-1, GPX4, γH2AX, 4HNE, 8-OHdG, Nrf2 antibodies were performed. ALOX5, FASN, GPX4 protein levels and GSH/GSSG ratio were measured. All results were evaluated statistically. While fasting blood sugar levels increased in the YF group, it was decreased in the YF-R group. At the end of the experiment, the body weight of group YF was decreased (p≤0.05). Fibrosis and iron accumulation were observed in the YF group, while fibrosis decreased and iron accumulation was not observed in the YF-R groups. The expressions of SIRT1(p<0.0001), GPX4(p<0.0001) and Nrf2(p≤0.05) were decreased in the YF group. COX2, HO-1, γH2AX, 4HNE and 8-OHdG expressions were increased in the YF group. There was no significant difference in ALOX5 and FASN levels, while GPX4 levels were lower in the YF group(p≤0.05) and GSH/GSSG levels increased in the YF (p<0.01) and YF-R (p<0.001) groups. In the study, it was determined that high fructose and low dose STZ increased blood sugar levels, stimulated oxidative stress and caused liver damage as a result of fibrosis in the liver, iron accumulation, DNA damage and increased expression of proteins involved in the ferroptosis pathway. It is thought that resveratrol reduces blood sugar levels, has a positive effect on oxidative stress, and protects liver tissue from ferroptosis by preventing iron accumulation in hepatocytes.