p38 MAPK Inhibitor (SB203580) and Metformin Reduces Aortic Protein Carbonyl and Inflammation in Non-obese Type 2 Diabetic Rats
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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.
KeywordsType 2 diabetes mellitus Vascular complications Protein carbonyl Inflammation Metformin SB203580
This thesis is sponsored and supported by National Research Council of Thailand. We would like to thank Naresuan University Research endowment fund Grant I.D. Numbers R2559A017, R2560C138. We would like to thank PhD scholarship from Naresuan University for Nuttikarn Nokkaew, Royal Golden Jubilee Ph.D. Program-Thailand Research Fund (TRF) (No. PHD/0087/2556) for Jantira Sanit and (No. PHD/0125/2558) for Kantapitch Kongpol. We are grateful to the Center for Animal Research, Naresuan University for their excellent technical assistance. We would like to thanks ProofRead4Sure service to English proof reading and editing.
NN, PM and SK conceived and designed the experiments; NN, RJ, SJ, NT, NM, NS, MI, JS, PA, and KK performed the experiments; NN, PM and SK analyzed the data; SK contributed reagents/materials/analysis tools; NN, NN and SK wrote and prepared the manuscript.
Compliance with Ethical Standards
Conflict of interest
The authors declare no conflict of interest.
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