p38 MAPK Inhibitor (SB203580) and Metformin Reduces Aortic Protein Carbonyl and Inflammation in Non-obese Type 2 Diabetic Rats

Nuttikarn Nokkaew; Podsawee Mongkolpathumrat; Ruttanapong Junsiri; Supawit Jindaluang; Nichagron Tualamun; Niya Manphatthanakan; Nareumon Saleesee; Marisa Intasang; Jantira Sanit; Punyanuch Adulyaritthikul; Kantapich Kongpol; Sarawut Kumphune; Nitirut Nernpermpisooth

doi:10.1007/s12291-019-0815-9

p38 MAPK Inhibitor (SB203580) and Metformin Reduces Aortic Protein Carbonyl and Inflammation in Non-obese Type 2 Diabetic Rats

Indian J Clin Biochem. 2021 Apr;36(2):228-234. doi: 10.1007/s12291-019-0815-9. Epub 2019 Jan 31.

Authors

Nuttikarn Nokkaew^{1

2}, Podsawee Mongkolpathumrat^{1

2}, Ruttanapong Junsiri², Supawit Jindaluang², Nichagron Tualamun², Niya Manphatthanakan², Nareumon Saleesee², Marisa Intasang², Jantira Sanit^{1

2}, Punyanuch Adulyaritthikul^{1

2}, Kantapich Kongpol^{1

2}, Sarawut Kumphune^{1

2

3}, Nitirut Nernpermpisooth^{1

2

4}

Affiliations

¹ Biomedical Research Unit in Cardiovascular Sciences (BRUCS), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok, 65000 Thailand.
² Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok, 65000 Thailand.
³ Department of Medical Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok, 65000 Thailand.
⁴ Department of Cardio-Thoracic Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok, 65000 Thailand.

Abstract

Microvascular and macrovascular diseases are the main causes of morbidity in type 2 diabetes patients through chronic hyperglycaemic condition via oxidative stress and inflammation. Reactive oxygen species (ROS) activate p38 MAPK phosphorylation and inflammation which enhances protein modification by carbonylation. The use of metformin and a p38 MAPK inhibitor is hypothesised to reduce ROS production and inflammation but effects of metformin and p38 MAPK inhibitor (SB203580) on ROS production and inflammation in vascular type 2 diabetes mellitus non-obese (T2DM) have not been investigated. The Goto-Kakizaki rat T2DM model was divided into three groups as T2DM, T2DM treated with 15 mg/kg bw metformin and T2DM treated with 2 mg/kg bw SB203580 for 4 weeks. Rat aortas were isolated and protein carbonyl (PC) contents were measured by spectrophotometric DNPH assay. Aortic IL-1ß level was determined by ELISA. Results showed that aortic PC contents in the T2DM group were significantly higher than in non-diabetic rats. Treatment with metformin or SB203580 significantly reduced PC contents while only metformin significantly reduced IL-1ß levels. Findings indicated that metformin reduced ROS production and inflammation in diabetic vessels and possibly reduce vascular complications in non-obese T2DM.

Keywords: Inflammation; Metformin; Protein carbonyl; SB203580; Type 2 diabetes mellitus; Vascular complications.