THE RENOPROTECTIVE EFFECTS OF TAURINE AGAINST DIABETIC NEPHROPATHY VIA P38 MAPK AND TGF-Β/SMAD2/3 SIGNALING PATHWAYS

This study aimed to investigate the possible renoprotective effectsof taurine via p38 MAPK and TGF-b/smad2/3 signaling pathways in a diabetic nephropathy model in rats. 29 Wistar albinorats were divided into 4 groups: control, taurine (1% with drinking water), diabetes (45 mg/kg Streptozotosin), diabetes+taurine.After 12 weeks, kidney and serum were collected for biochemicaland histological studies. The histological analysis showed thatthere were significant changes in tubule dilatation and loss oftubule brush border in the kidney of the diabetes group. Thesechanges were significantly decreased with taurine. However, therewere no significant changes in serum creatinine and blood urinenitrogen levels among groups. Further, taurine significantlyreduced the protein expression of NADPH oxidase 4, known asa major enzymatic source for oxidative stress in the kidney. Also,there was a significant decrease in reactive oxygen species andmalondialdehyde levels by taurine whereas the decreased superoxide dismutase activity level in the diabetes group was significantly increased with taurine. On the other hand, taurine resultedin significant decreases in both mRNA and protein expression offibronectin, which is a major extracellular matrix protein relatedto the fibrosis process, These findings were parallel to MassonTrichrome staining. The matrix metalloproteinases (MMP)-2 andMMP-9 mRNA expression levels and their activities increasedsignificantly in diabetes compared to the control, and theseincreases were significantly reached to higher levels with taurine.Also, the decreased mRNA expression of extracellular matrixmetalloproteinase inducer (EMMPRIN) increased with taurine inthe diabetes+taurine group. Moreover, it is found that taurinesuppressed the p38 MAPK and TGF-b/smad2/3 signaling pathways. All these findings indicate that taurine may be an effectivepractical strategy to prevent renal diabetic injury