Oxidative stress and inflammatory marker: possible pathogenic role in acute coronary syndrome

Acute coronary syndrome [ACS], which comprise unstable angina [UA] and acute myocardial infarction [AMI] are multifactor diseases involving both thrombotic and inflammatory processes. C-reactive protein [CRP] has emerged as independent risk indicator of active atherosclerosis. Reactive oxygen species [ROS] are key mediators of signaling pathways that underlie vascular inflammation in atherogenesis starting from the initiation of fatty streak development through lesion progression to ultimate plaque rupture. CRP directly up-regulate AND[P]H oxidase p22 [phox] and enhance ROS generation. Recently it has been shown that 8-iso-prostaglandin F2 alpha [8-iso-PGF2_] is a specific, chemically stable and quantitative marker of oxidative stress in vivo. It is formed in situ in cell membranes following free radical attack on the arachidonic acid. To counteract the effect of ROS, cells are endowed with a complex antioxidant network that operates to prevent or limit oxidant damage. The present study was designed to investigate the changes of 8-iso-PGF2_, total antioxidant capacity [TAC] and CRP levels in patients with acute coronary syndrome in order to evaluate the role of oxidative stress as well as inflammation in pathogenesis and consequence of the disease. The present study included 30 patients with ACS and 15 healthy, age and sex-matched controls. The patients were divided into two groups; 15 patients with UA and 15 patients with AMI. Serum leuel of 8-iso-PGF2-_ was measured using an ELISA kit Serum CRP and TAC levels was measured by turbidimetric immunoassay and colorimetric methods respectively. Serum levels of both 8-iso-PGF2- _, and CRP were significantly increased in patients compared with control [p<0.05]. TAG showed significant decrease in patients with AMI when compared to controls [p<0.05]. It could be concluded that elevated levels of 8-iso-PGF2-_ and CRP together with decreased TAC level contribute directly and actively to the pathogenesis of ACS. The oxidative stress is likely to either induce or intensify the inflammatory action, and may co-affect with inflammatory factors to accelerate plaque rupture. The evaluation of oxidative stress would enable formulation of specific antioxidant therapy as promising strategy against atherogenesis for an early intervention and better management of the disease

Renoprotective effect of leflunomide against ischemia-reperfusion injury in rats

Renal ischemia is of great clinical interest because of its role in renal failure and renal graft rejection. The purpose of this study was to investigate the possible protective effect of leflunomide against ischemia/ reperfusion [l/R] injury in the rat. Three groups of Sprague-Dawley rats [10 rats each], the control group, I/R group and the leflunomide- treated I/R group. A renal I/R injury were induced by a left renal pedicle occlusion to induce ischemia for 45 min, followed by 60 mins of reperfusion with contralateral nephrectomy in rats. The rats in Leflunomide treated I/R group were pretreated intra- gastrically with a leflunomide suspension [10 mg/kg] 60 min before the- ischemia induction. Thiobarbituric acid reactive substances [TBARS], nitric oxide [NO], tumor necrosis factor alpha [TNF-alpha], catalase [CAT] superoxide dismutase [SOD] activities were determined in renal tissue, while, creatinine, blood urea nitrogen [BUN] were measured in blood. Our results indicate that TBARS, NO, TNF-[alpha], BUN and creatinine levels were significantly higher in the I/R group than those in the control group. Leflunomide administration significantly decreased these parameters. SOD and CAT activities significantly decreased after I/R injury when compared to the control group. Leflunomide treatment significantly increased activities of these enzymes when compared to the I/R group. These results demonstrated that reactive oxygen species [ROS] and TNF-alpha play causal role in I/R induced renal injury and leflnomide exerted renoprotective effects by anti-inflammatory effect with radical scavenging and antioxidant activities

Assessment of propertide of type III procollagen in chronic liver diseases

Sixty-three hepatic patients [38 males and 25 females] with ages ranging between 25-75 years [mean 48.49 +/- 1.72] were included in this study. For comparison, 20 healthy age and sex matched volunteers were taken as controls. Patients with chronic liver diseases including hepatic cirrhosis [23 patients], bilharzial hepatic fibrosis [10 patients], hepatic malignancy [15 patients] and chronic viral hepatitis C [15 patients] were included in this study. All patients and healthy subjects were thoroughly clinically examined. Fasting blood sample was taken from each individual, divided into aliquots and analyzed for aminoterminal propeptide of type IIII procollagen and liver function tests [including prothrombin time, serum albumin, bilirubin, ALT and AST]. The severity of liver disease was graded by Pugh-Child scoring including the assessment of ascites, encephalopathy, bilirubin, albumin and prothrombin time. It was concluded that propeptide of type III procollagen [PIIINP] measurement is a good noninvasive marker of manifest fibrosis. Cirrhotic patients had the highest serum PIIINP levels of all studied patients