الفهرس 
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Abstract
The present study was conducted to investigate the role of hydrogen sulfide (H2S) on the diabetes-associated cardiovascular dysfunction and nephropathy. This study was aimed to elucidate the role of nitric oxide on the protective effects of H2S. The protective effects of H2S were tested by administration of L-cysteine as an endogenous precursor for H2S production and NaHS as an exogenous source of H2S. To test the dependency of H2S on NO availability, L-NAME was combined with NaHS. In order to emphasize the role of H2S in the protection against adverse diabetes outcomes, an inhibitor of H2S synthesis was utilized in this study.
The results of this study showed that:
Diabetes model showed an increase in insulin resistance, oxidative stress, and serum lipids and caused a state of inflammation.
Diabetes induction resulted in elevated serum levels of urea and creatinine. In addition to a reduction of NO bioavailability and protein expression of eNOS in the aortic tissue of diabetic rats, diabetes led to impaired relaxation response of aortic rings to Ach (i.e. endothelial dysfunction).
On the other hand, treatments with L-CYS or NaHS improved insulin resistance, lipid profile and diminished level of H2O2 production. Nitrite/nitrates levels and eNOS protein expression returned to their normal values in L-CYS and NaHS treated groups. H2S donors possessed anti-inflammatory effects evident in their effects on TNF-α and NF-κB level. All these actions contributed to significant improvement in vascular activity function in NaHS and L-cysteine treated groups. L-CYS and NaHS treatment resulted in an improvement of cardiomyopathy and nephropathy induced by diabetes.
Administration of L-NAME with NaHS attenuated the protective effects of NaHS on inflammatory and oxidative status. In addition, inhibition of H2S synthesis resulted in deterioration of endothelial function, cardiac and kidney function markers along with amelioration of insulin resistance, hyperlipidemia and inflammatory status.
In conclusion, our study demonstrates that H2S plays a crucial role in protection aganist diabetes and its cardiovascular and renal complications. The protective mechanisms of H2S are probably attributed to its anti-inflammatory and antioxidant properties, alongside regulation of NO signaling pathway. Therefore, H2S may represent a promising therapeutic target for management of diabetic complications.