Selçuk İlhan

Irisin: a potentially candidate marker for myocardial infarction.

Myocardial infarction (MI) causes energy depletion through imbalance between coronary blood supply and myocardial demand. Irisin produced by the heart reduces ATP production by increasing heat generation. Energy depletion affects irisin concentration in circulation and cardiac tissues, suggesting an association with MI. We examined: (1) irisin expression immunohistochemically in rat heart, skeletal muscle, kidney and liver in isoproterenol (ISO)-induced MI, and (2) serum irisin concentration by ELISA. Rats were randomly allocated into 6 groups (n=6), (i) control, (ii) ISO (1h), (iii) ISO (2h), (iv) ISO (4h), (v) ISO (6h), and (vi) ISO (24h), 200mg ISO in each case. Rats were decapitated and the blood and tissues collected for irisin analysis. Blood was centrifuged at 1792 g for 5 min. Tissues were washed with saline and fixed in 10% formalin for histology. Serum irisin levels gradually decreased from 1h to 24h in MI rats compared with controls, the minimum being at 2h, increasing again after 6h. Cardiac muscle cells, glomerular, peritubular renal cortical interstitial cells, hepatocytes and liver sinusoidal cells and perimysium, endomysium and nucleoi of skeletal muscle were irisin positive, but its synthesis decreased 1-4h after MI. At all time-points, irisin increased near myocardial connective tissue, with production in skeletal muscle, liver and kidney recovering after 6h, although slower than controls. Unique insight into the pathogenesis of MI is shown, and the gradually decrease of serum irisin might be a diagnostic marker for MI.

Protective effect of caffeic acid phenethyl ester on cyclosporine A-induced nephrotoxicity in rats.

Introduction. Cyclosporine A, an immunosuppressive agent, is widely used after organ transplantation such as the liver and kidney. However, its widespread use is restricted because it has serious toxic effects on the kidney. Caffeic acid phenethyl ester (CAPE) is a natural product with potent anti-inflammatory, antitumor, and antioxidant activities, and it attenuates inflammation and lipid peroxidation induced by ischemia-reperfusion injury. The purpose of the present study was to investigate the effects of CAPE on cyclosporine A (CsA)-induced nephrotoxicity. Material and Methods. Rats were divided into four groups and treated with saline, CAPE, CsA, and CsA + CAPE. Control rats were given saline; the CAPE group was given CAPE (10 μmol/kg/day) for 11 days intraperitoneally; the CsA group was given CsA (15 mg/kg/day) for 10 days subcutaneously; and the CsA+CAPE group was given CAPE for 11 days, and rats were s.c. injected with CsA in 0.5 ml of saline once a day for 10 days at the same time. Results. The administration of CsA alone resulted in higher myeloperoxidase (MPO) activity, lipid peroxidation, superoxide dismutase (SOD), and catalase (CAT) than in the control. The enzyme activities except CAT in rats treated with CAPE alone were not changed. CAPE treatment prevented the increase in malondialdehyde (MDA) and increased CAT activity more, but did not affect the activities of MPO and SOD enzymes. Discussion. CsA causes renal injury and CAPE prevents CAT- and lipid peroxidation-mediated nephrotoxicity via inhibition of oxidative process.

The Investigation of Serum Vaspin Level in Atherosclerotic Coronary Artery Disease

Background It was speculated that fatty tissue originated adipocytokines may play role in pathogenesis of atherosclerosis. These adipocytokines may alter vascular homeostasis by effecting endothelial cells, arterial smooth muscle cells and macrophages. Vaspin is a newly described member of adipocytokines family. We aimed to investigate whether plasma vaspin level has any predictive value in coronary artery disease (CAD). Methods Forty patients who have at least single vessel ≥ 70 % stenosis demostrated angiographically and 40 subjects with normal coronary anatomy were included to the study. The vaspin levels were measured from serum that is obtained by centrifigation of blood and stored at -20 oC by ELISA method. The length, weight and body mass index of patients were measured. Biochemical parameters including total cholesterol, low density lipoprotein, high density lipoprotein, creatinine, sodium, potassium, hemoglobine, uric acid and fasting glucose were also measured. Results Biochemical markers levels were similar in both groups. Serum vaspin levels were significantly lower in CAD patients than control group (respectively; 256 ± 219 pg/ml vs. 472 ( 564 pg/ml, P < 0.02). Beside this serum vaspin level was lower in control group with high systolic blood pressure. Conclusion Serum vaspin levels were found significantly lower in patients with CAD than age-matched subjects with normal coronary anatomy. Vaspin may be used as a predictor of CAD. Keywords Coronary artery disease; Vaspin; Adipokine

Ceftriaxone ameliorates cyclosporine A-induced oxidative nephrotoxicity in rat.

A growing body of evidence now suggested that cyclosporine A (CycA)‐induced nephrotoxicity is a crucial clinical problem and oxidative stress is importantly responsible for its toxicity. Ceftriaxone induced antioxidant effect in brain and neuronal tissues against oxidative damage although its antioxidant potential effect on kidney has not been clarified. The aim of this study was to evaluate whether ceftriaxone protects CycA‐induced oxidative stress kidney injury in rats. Twenty‐four rats were equally divided into four groups. First group was used as control. Ceftriaxone (200 mg/kg) and CycA (15 mg/kg) were administrated to second and third groups for 10 days, respectively. The ceftriaxone and CycA combination was given to rats constituting the fourth group for 10 days. Lipid peroxidation (LP), urea nitrogen and lactate dehydrogenase (LDH) levels were higher in CycA group than in control and ceftriaxone groups although LP, urea nitrogen and LDH levels were lower in ceftriaxone + CycA group than in control and ceftriaxone groups. Glutathione peroxidase and catalase activities were lower in CycA group than in control whereas their activities were increased in control and ceftriaxone groups. Superoxide dismutase activity did not change by the treatments. Ceftriaxone administration recovered also CycA‐induced atrophy, vacuolization and exfoliations of tubular epithelium and glomerular collapse in histopathological evaluation of kidney. In conclusion, we observed that ceftriaxone is beneficial on CycA‐induced oxidative stress in kidney of rats by modulating oxidative and antioxidant system. Copyright

2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced hypertension The beneficial effects of melatonin

Objective: The purpose of the present study was to evaluate the effects of melatonin on biochemical and cardiovascular changes resulting from exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a polychlorinated dibenzo-para-dioxin. Methods: A total of 24 Sprague-Dawley rats were divided equally into the following four groups: (1) control group was administered with 0.5 mL corn oil by gavage and 0.5 cc vehicle of melatonin (proportionally nine parts physiological serum + one part ethyl alcohol) intraperitoneally for 4 weeks, (2) the melatonin group was given 5 mg/kg/day melatonin intraperitoneally for 4 weeks, (3) the TCDD group was given 500 ng/kg/day TCDD by gavage for 4 weeks and (4) the TCDD + melatonin group was given TCDD (500 ng/kg/day) by gavage and melatonin (5 mg/kg/day) intraperitoneally simultaneously for 4 weeks. Systolic blood pressure was evaluated by the tail-cuff method. Vascular responses to phenylephrine and acetylcholine were evaluated in the isolated thoracic aortas. Results: TCDD not only augmented the systolic blood pressure but also increased the contractile responses to phenylephrine in aorta. Melatonin reversed the blood pressure augmented by TCDD and decreased the contractile responses to phenylephrine in aorta. TCDD induced an increase in the malondialdehyde levels in kidney tissue and melatonin did not change it. Therefore, TCDD caused a decrease in glutathione levels in kidney tissues and melatonin reversed it. Conclusion: Present data demonstrated that TCDD may lead to an increase in blood pressure via increased renal oxidative stress and vascular reactivity. However, melatonin might ameliorate the blood pressure disturbed by TCDD in part by decreasing the oxidant activity induced by TCDD.

Protective effects of caffeic acid phenethyl ester on iron-induced liver damage in rats

Caffeic acid phenethyl ester (CAPE) is a natural product with potent anti-inflammatory, antitumor, and antioxidant activities, and attenuates inflammation and lipid peroxidation. The purpose of the present study was to investigate the effects of CAPE on iron-induced liver damage. Rats were divided into four groups and treated for 7 days with saline (control group), 10 µmol kg CAPE/day s.c. (CAPE group), 50 mg iron-dextran/kg i.p. (IRON group) and CAPE and iron at the same time (IRON+CAPE group). Seven days later, rats were killed and the livers were excised for biochemical analysis. The administration of IRON alone resulted in higher myeloperoxidase (MPO) activity and lipid peroxidation than in the control and CAPE treatment prevented the increase in MPO activity and malondialdeyde (MDA) level. No differences were observed in all four groups with regards to superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities. Our results collectively suggest that CAPE may be an available agent to protect the liver from injury via inhibition of MPO activity.

Salt and Nitric Oxide Inhibition Induced Hypertension: The Role of Prostacycline and 8-Isoprostane

Renal prostacycline (PGI2) and oxidative stress are known to be important factors that effect the natriurezis and diuresis. 8-iso prostaglandin F2α± (8-isoprostane), a member of F2-isoprostanes, is formed from the nonenzymatic reaction of arachidonic acid and oxygen radicals in vivo and in vitro, and also it is a marker of oxidative stress in vivo. The aim of this study is to determine the role of renal PGI2 and 8-isoprostane in a salt and nitric oxide (NO) inhibition-induced hypertension model. Rats were distributed equally among four groups (n = 6 per group). Control rats were given normal salt diet (0.32%); high-salt (HS) rats were given high salt diet (3.2%); NG-nitro-L-arginine (L-NNA) rats were given normal salt diet and 25 mg/kg L-NNA; HS+L-NNA rats were given high salt diet and 25 mg/kg L-NNA. Rats were placed in individual metabolic cages for 17 days. Systolic blood pressure (SBP) was measured at days initial, 7th and 14th .Urinary 8-isoprostane and PGI2 levels were analyzed. Salt- loading alone did not change SBP values. The average SBP in L-NNA and HS+L-NNA groups were shown to significantly enhance compared to initial and day 7th in the same groups, respectively. The levels of 8-isoprostane in the HS+L-NNA group was significantly enhanced compared to the other groups. L-NNA or HS diet alone did not change the levels of 8-isoprostane compared to the control group. L-NNA alone did not change PGI2 levels in urine compared to the control. PGI2 levels in the HS, and the HS+L-NNA group was significantly higher compared to the control group. This study concluded that NOS inhibition plus salt-loading induced oxidative stress and increased renal PGI2. Also, it is suggested that augmented oxidative stress may aggravate the hypertension. But the renal synthesis of PGI2 is increased in order to augment the diuresis and natriuresis without the effect of blood pressure (BP).

Effects of caffeic acid phenethyl ester on isoproterenol-induced myocardial infarction in rats

OBJECTIVE Caffeic acid phenethyl ester (CAPE) is a natural product with potent anti-inflammatory, antitumor and antioxidant activities and attenuates inflammation and lipid peroxidation induced by ischemia-reperfusion injury. The purpose of the present study was to investigate the effects of CAPE on isoproterenol (ISO) -induced myocardial infarction. METHODS A randomized controlled experimental design was used in this study. Rats were divided into four groups and treated with saline, CAPE, ISO and ISO+CAPE. Rats were treated with CAPE (10 micromol kg/day i.p.) or saline starting 3 days before injecting ISO (150 mg /kg s.c., 24 hours). Seven days later, rats were sacrificed and the hearts were excised for biochemical analyses and microscopic examination. One-way ANOVA test with post hoc multiple comparisons using LSD method were used for statistical analysis of the data. RESULTS The administration of ISO alone resulted in higher myeloperoxidase (MPO) activity, lipid peroxidation, superoxide dismutase (SOD) and catalase (CAT) than in the control. The enzyme activities did not change in rat given CAPE alone. CAPE treatment prevented the increase in MPO activity and malondialdehyde, but did not affect the activities SOD and CAT enzymes. CONCLUSION In light of these results, we conclude that CAPE prevents MPO-and lipid peroxidation-mediated myocardial injury via inhibition of neutrophils MPO activity.

The effect of caffeic acid phenethyl ester on isoproterenol-induced myocardial injury in hypertensive rats.

OBJECTIVE The aim of this study is to investigate the effects of caffeic acid phenethyl ester (CAPE) on isoproterenol (ISO)-induced myocardial injury in hypertensive rats. METHODS Rats were divided into 4 groups (n=29): Control group (n=8), L-NNA (NG-Nitro-L-arginine) group (n=8), L-NNA+ISO (L-NNA+isoproterenol) group (n=7) and L-NNA+ISO+CAPE (L-NNA+ISO + caffeic acid phenethyl ester) group (n=6). ISO (150 mg/kg/day) was given intraperitoneally (i.p.) once a day for 2 consecutive days (at the 12th and 13th days of L-NNA treatment). NG-Nitro-L-arginine (L-NNA) was given orally (25 mg/kg/day) in drinking water for 14 days. CAPE (10 μmol/kg/day) was given (i.p.) for 7 days after the first week. Systolic blood pressure (SBP) was evaluated by the tail-cuff method and biochemical analysis were performed using an autoanalyzer and a spectrophotometer. RESULTS SBP in all L-NNA-treated groups was found to be increased at seventh day. AST and LDH levels in LNNA+ISO group were significantly increased compared to control (AST: 125±5 vs. 105±2; LDH: 861±154 vs. 571±46 U/L respectively) (p<0.05). Also, ISO caused to extensive necrosis and mononuclear cell infiltration in hypertensive rat myocardium. CAPE application reversed the enhanced AST and LDH levels as well as the extensive necrosis and the mononuclear cell infiltration in LNNA+ISO+CAPE group compared LNNA+ISO. CONCLUSION According to our findings, it might be suggested that CAPE may be a favorable agent to protect the hypertensive myocardium from the injury induced by isoproterenol via mechanisms such as the induction of the antioxidant enzymes and the inhibition of lipid peroxidation.

Salt and nitric oxide synthase inhibition-induced hypertension: kidney dysfunction and brain anti-oxidant capacity.

The specific aim of this study was to examine the effects of salt-loading on kidney function and brain antioxidant capacity. Wistar rats were divided into four groups: Control rats were given normal drinking water and no drug treatment for 2 weeks. LNNA group: rats were given normal drinking water and the nitric oxide (NO) inhibitor NG-nitro-L-arginine (L-NNA), 3 mg/kg/day. LNNA + Salt group: rats were given drinking water containing salt 2% and 3 mg/kg L-NNA. Salt group: rats were given drinking water containing salt 2% and no drug treatment. Basal blood pressure and the levels of serum BUN, creatinine, uric acid, cortisol, electrolyte, serum antioxidant capacity, and oxidative stress were measured. NO, superoxide dismutase (SOD), and catalase (CAT) levels were measured in the hypothalamus, brainstem, and cerebellum. Salt overload increased the blood pressure of the LNNA + Salt group. Salt-loading enhanced BUN, creatinine, sodium retention. High salt produced an increase in uric acid levels and a decrease in cortisol levels in serum. Additionally, the oxidative stress index in serum increased in the LNNA + Salt group. Salt-loading enhanced brain NO levels, but not SOD and CAT activity. L-NNA increased brain SOD activity, but not CAT and NO levels. In conclusion, salt-loading causes hypertension, kidney dysfunction, and enhances oxidative stress in salt-sensitive rats.