Anti-diabetic drug, metformin, and the p38 inhibitor (SB203580) reduces internal organs oxidative stress in non-obese type 2 diabetic rats

Abstract

Diabetic complications caused by hyperglycemia and oxidative stress, which can activate p38 mitogen-activated protein kinase (p38 MAPK), and aggravate complications via the enhancement of reactive oxygen species (ROS) generation. Recently, metformin or p38 MAPK inhibitors could reduce ROS production in particularly protein carbonylation, in diabetic vessel. However, the combinatorial effect of metformin and SB203580 on internal organ oxidative stress in non-obese (lean) type 2 diabetes mellitus (T2DM) is still uncleared. In this study, Goto-Kakizaki rats were divided into four groups, including control diabetic group, metformin-treated group, p38 MAPK inhibitor (SB203580)-treated group, and combination between metformin and p38 MAPK inhibitor (SB203580). Internal organ protein from kidney, pancreas, liver, and brain was determined for protein carbonyl (PC) content by spectrophotometric 2, 4-Dinitrophenylhydrazine assay. There was an increase in PC content levels in the serum and internal organs of T2DM. Metformin ameliorated PC content in serum and internal organs. However, SB203580 could only reduce the PC content in the liver. The combination of metformin and SB203580 could synergistically reduce the PC content levels in serum but not the internal organs. In summary, metformin provided the greatest potential for reducing oxidative stress, while SB203580 or combined metformin with SB203580 could not reduce oxidative stress in the internal organs of non-obese type 2 diabetic rats.