Abstract
Hyperglycemia caused by diabetes mellitus, in sensitive tissues such as the kidney, can cause dysfunction by damaging the blood vessels. Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, play a significant role in the degradation of proteins and angiogenesis; while epidermal growth factor receptor (EGFR) is involved in the recovery of damaged tissues. Herein, we investigated the relationship between MMP-2 and MMP-9 / EGFR in the kidney tissues of streptozotocin-induced Wistar male rats. We also examined the effects of resveratrol known as a strong tissue-protective on these changes. Diabetes was induced by streptozotocin (55 mg/kg) and trans-resveratrol (20 mg/kg/day intraperitoneal) was used for treatment. Rats were divided into 4 groups as control, resveratrol (Res), diabetes (Diab) and diabetes plus resveratrol (Diab+Res). Superoxide dismutase (SOD) and catalase (CAT) levels were significantly decreased in the kidneys in the diabetic group, whereas nitrite / nitrate, urea, creatine kinase (CK) and uric acid concentrations increased. MMP-2, MMP-9, calcium-binding protein B (S100B) and platelet-derived growth factor (PDGF) concentrations of kidney were increased although reduced EGFR in the diabetes group. Resveratrol supplementation markedly restored all these structures. Diabetes activates MMP related inflammation and oxidative stress by suppressing antioxidant enzymes in the kidney tissues. Resveratrol has partly modulatory effects on diabetes-induced changes.
Highlights
Matrix metalloproteinases (MMPs) are a family of zincdependent proteinases involved in remodeling the extracellular matrix
Hyperglycemia and free oxygen reagents increase MMP-2 and MMP-9 levels by inducing MEK/extracellular signal-regulated kinase (ERK)/NfκB pathway and often result in diabetic retinopathy (Renu, 2017; Ankita, 2019). It has been shown in many studies that diabetes-induced hyperglycemia increases the levels of end products Cystatin-C, creatine kinase (CK), urea and uric acid (Adlija, 2006; Talib, 2012; Qian, 2017) by enhancing the levels of oxidative markers such as nitrite/nitrate (Naseer, 2014)
The body weights in the diabetes group were significantly lower than those of control rats and unchanged after resveratrol supplementation (Table 1)
Summary
Matrix metalloproteinases (MMPs) are a family of zincdependent proteinases involved in remodeling the extracellular matrix. Hyperglycemia and free oxygen reagents increase MMP-2 and MMP-9 levels by inducing MEK/ERK/NfκB pathway and often result in diabetic retinopathy (Renu, 2017; Ankita, 2019). It has been shown in many studies that diabetes-induced hyperglycemia increases the levels of end products Cystatin-C, creatine kinase (CK), urea and uric acid (Adlija, 2006; Talib, 2012; Qian, 2017) by enhancing the levels of oxidative markers such as nitrite/nitrate (Naseer, 2014). EGFR is a tyrosine kinase receptor expressed in the kidney and activated after renal damage (Yoshioka, 1990). This receptor plays a key role in renal electrolyte homeostasis. Its role in renal pathology is somewhat contradictory since both beneficial and deleterious actions have been found
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