الفهرس 
Introduction and Aim of the workOnly 14 pages are availabe for public view
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Abstract
In this setting, the present study aimed to recognize the exact role of hemoxgenase-1 (HO-1) enzyme in DN through employing HO-1 inducer; hemin (HM) and HO-1 inhibitor; zinc protoporphyrin-IX (ZnPP). Also, this study aimed to investigate the protective role of rosuvastatin (RSV) as one member of statin group of drugs in DN through HO-1 pathway.
The results of the present study revealed that:
- Administration of a single dose of STZ showed marked elevation in blood glucose, marked body weight loss, and developed DN as one of diabetic complication evidenced by renal kidney dysfunction with histopathological kidney structure as compared to control group.
- Dyslipidemia in STZ-induced diabetic rats was observed and characterized by significant increase in serum levels of TC, TG and LDL-C, while HDL-C level was decreased compared to control group.
- Functional impaired kidney evidenced by elevated levels of serum creatinine, urea and urine albumin to creatinine ratio (ACR) compared to control group with significant reduced serum albumin in addition to hyperkalemia and sodium retention.
- Oxidative stress was markedly increased which manifested by increased renal contents of MDA and NO with increased MPO activity along-side with reduced antioxidant CAT and SOD activities, as well as, decreased levels of reduced GSH.
- DN is characterized by inflammation, as well as, apoptosis evidenced by elevated renal protein expression of both TNF-α and caspse-3.
- Treatment with either HM or RSV to STZ-induced diabetic rats significantly ameliorated renal dysfunction and also improved lipid profile as illustrated by reduction in serum TC, TG and LDL-C and increase in HDL-C.
- Furthermor, treatment with either HM or RSV to STZ-induced diabetic rats inhibited the state of oxidative stress in renal tissue compared to non-treated STZ-induced DN rats.
- In addition, treatment with either HM or RSV to STZ-induced diabetic rat improved renal inflammation and apoptotic status that is proposed to be the main cause of renal tissue damage.
- Also, treatment with either HM or RSV to STZ-induced diabetic rat increased HO-1 protein expression and activity, while ZnPP showed up-regulation with no increased activity.
- ZnPP treatment alone or combined with either HM, RSV, or HM + RSV, abolished the beneficial effects encountered by HM or RSV or both together.
In conclusion, our results suggested that hyperglycemia-induced ROS developed DN through stimulation of gene expression of inflammatory cytokines that resulted in apoptotic tissue degeneration. HO-1 possess a triad actions including antioxidant, anti-inflammatory, as well as, antiapoptotic effect and showed efficiency in ameliorating hyperglycemic insults to kidney tissue with improved kidney function .
RSV treatment showed similar effects along-side with increased HO-1 protein expression and activity, suggesting that the protective pleiotropic effects of RSV, apart from lipid lowering effects, may be exhibited through modulating HO-1 expression and activity as one main arm for its action.