Eser Öz

Prevention of doxorubicin-induced cardiotoxicity by melatonin

Anthracyclines, such as doxorubicin and daunorubicin, are highly effective anticancer agents. Cardiotoxicity made by these agents develops as a complication of the cancer chemotherapy. Melatonin, the chief secretory product of the pineal gland, was recently found to be a free radical scavenger and antioxidant. We decided to evaluate the tissue-protective effect of melatonin against myocardial toxic effects of doxorubicin in six groups of rats. Rats were given doxorubicin (Dx) (45 mg/kg dose) and melatonin (MEL) (10 mg/kg), first doxorubicin and then melatonin (DM), first melatonin and then doxorubicin (MD). The degree of cardiac muscle cell alterations were examined either histologically (mean total score technique) or biochemically. In doxorubicin-treated group, malondialdehyde (MDA) levels of the heart tissue were significantly increased, glutathione (GSH) levels were decreased compared to the control rats. In the group in which first doxorubicin and then melatonin was given, MDA levels were significantly decreased and glutathione (GSH) levels were increased compared to the doxorubicin-treated group. During ultrastructural analysis, in doxorubicin-treated group, cellular edema, mitochondrial deformation, decreased glycogen stores, and disordered myofibrillary structure were observed. In contrast, in first doxorubicin and then melatonin-treated group, normal cellular structure was observed. But, first melatonin and then doxorubicin-treated group was not significantly preserved from the doxorubicin-induced changes. By preventing lipid peroxidation and myocardial lesions, melatonin may be highly effective in protecting against doxorubicin-induced cardiotoxicity.

The effect of taurine on renal ischemia/reperfusion injury

Summary.Ischemia-reperfusion (I/R) injury is one of the most common causes of renal dysfunction. Taurine is an endogenous antioxidant and a membrane-stabilizing, intracellular, free beta-amino acid. It has been demonstrated to have protective effects against I/R injuries to tissues other than kidney. The aim of this study was to determine whether taurine has a beneficial role in renal I/R injury. Forty Wistar-Albino rats were allocated into four groups as follows: sham, taurine, I/R, and I/R + taurine. Taurine 7.5 mg/kg was given intra-peritoneally to rats in the groups taurine and I/R + taurine. Renal I/R was achieved by occluding the renal arteries bilaterally for 40 min, followed by 6 h of reperfusion. Immediately thereafter, blood was drawn and tissue samples were harvested to measure 1) serum levels of BUN and creatinine; 2) serum and/or tissue levels of malondialdehyde (MDA), glutathione (GSH), glucose 6-phosphate dehydrogenase (G-6PD), 6-phosphogluconate dehydrogenase (6-PGD) and glutathione reductase (GSH-red); 3) renal morphology; and 4) immunohistochemical staining for P-selectin. Taurine administration reduced I/R-induced increases in serum BUN and creatinine, and serum and tissue MDA levels (p < 0.05). Additionally, taurine lessened the reductions in serum and tissue glutathione levels secondary to I/R (p < 0.05). Taurine also attenuated histopathologic evidence of renal injury, and reduced I/R-induced P-selectin immunoreactivity (p < 0.05). Overall, then, taurine administration appears to reduce the injurious effects of I/R on kidney.

Taurine and calcium interaction in protection of myocardium exposed to ischemic reperfusion injury

We aimed to investigate the cardio-protective role of taurine with low calcium level against reperfusion damage by adding taurine to extracellular fluid. Guinea-pig hearts were mounted on Langendorf perfusion apparatus and different compositions of perfusion solutions were prepared for each experimental group. After 20 min of normothermic ischemia the hearts were reperfused. Pre-ischemic, post-ischemic and post-reperfusion percentage changes of heart rate and contractile force were compared. Post-reperfusion tissue weight, malondialdehyde (MDA) and prostaglandin E-like activity (PGE-like activity) were assessed. Taurine-added low-calcium perfusion solution significantly decreased the postischemic myocardial injury.

Effects of Ischemic Preconditioning in Human Heart

Abstract  Background: The aim of this study is to investigate the effects of ischemic preconditioning (IP) on myocardium and the level of nitric oxide (NO) in patients undergoing aorta‐coronary bypass surgery. Methods: Twenty consecutive patients with coronary artery disease were subjected into two equal groups; the IP group and the control group. Following the onset of cardiopulmonary bypass in the study group, hearts were preconditioned with two 3‐minute periods of cross‐clamping separated by 2 minutes of reperfusion. In the control group, cardiopulmonary bypass was continued for 10 minutes without using cross‐clamp. Arterial and coronary sinus blood samples were used to determine serum NO, malondialdehyde (MDA), creatine phosphokinase‐MB (CKMB), and lactate dehydrogenase (LDH) levels. Need for defibrillation after cross‐clamp removal, ECG changes, postoperative arrhythmias, ejection fraction, and fractional shortening rates were recorded as hemodynamic data. Results: Serum NO level was higher in the study group 5 minutes after aortic clamp removal (199.3 ± 92.7 vs. 112.2 ± 35.8 μmol; p = 001). Serum MDA (2.55 ± 0.4 vs. 4.06 ± 0.5; ηmol/ml; 5 minutes after the aortic clamp removal; p = 0.0002); CK‐MB (22.8 ± 2.5 vs. 37.4 ± 4.1; U/L 12 hours after the operation, p < 0.0001), and LDH (501.8 ± 46.7 vs. 611.4 ± 128.3; IU/L 48 hours after the operation, p = 0.02) levels were significantly lower in the preconditioned group when compared with the control group. Also, need for electrical defibrillation was significantly lower in the study group; Ejection fraction (64.3 ± 6.3 vs. 57.6 ± 7.6; p = 0.04) and fractional shortening (31.7 ± 3.9 vs. 26.2 ± 4.0; p = 0.04) rates were better in the study group postoperatively. Conclusions: These data may suggest that cardioprotection by ischemic preconditioning offers higher NO production, a lower myocardial ischemia, and better functional recovery of the hearts in coronary artery surgery patients.

The effect of selenium added cardioplegia in guinea pigs

1. The aim of the study was to determine the effect of selenium added cardioplegic solutions on postischemic myocardial recovery. 2. The hearts were mounted on Langendorf perfusion apparatus and perfused with Krebs-Henseleit solution. The hearts were arrested by one of the following cardioplegic solutions; (a) K+ 20 mmol/l (control group); (b) K+ 20 mmol/l+selenium 10(-3) mol/l (experimental group). After 20 min of normothermic ischemia the hearts were reperfused by the same buffer. 3. Postischemic percentage changes of heart rate, contractile force and heart work were compared between the groups. 4. Addition of selenium to the cardioplegic solution significantly decreased the postischemic myocardial injury.

The role of selenium added to pulmonary preservation solutions in isolated guinea pig lungs

An experimental comparative study on isolated guinea pig lungs has been undertaken to determine the probable beneficial effects of adding selenium to pulmonary preservation solutions in lung ischemia. The isolated lungs (n = 10 in each group) previously being perfused by oxygenated Krebs-Henseleit solution were put in normothermic ischemic conditions just after the infusion of 30 ml of pulmonary preservation solution (Euro-Collins in the control group, Euro-Collins plus selenium 10(-3) mol in the experiment group). After 3 hours of normothermic ischemia the lungs were reperfused with the same buffer for 20 minutes. Pulmonary artery pressures, tissue malondialdehyde levels, and adenosine deaminase levels of the perfusate were measured before and after the ischemic period and also at the end of reperfusion. An electron microscopic analysis was performed on the lung tissues at the end of the experimental procedure. According to our data, the addition of selenium to pulmonary preservation solution showed a significant protective effect regarding both ischemic and reperfusion injury.

The role of taurine added to pulmonary reperfusion solutions in isolated guinea pig lungs

Summary. An experimental comparative study on isolated guinea pig-lungs has been undertaken to determine the probable beneficial effects of adding taurine to pulmonary reperfusion solutions in lung ischemia-reperfusion. 20 guinea pigs were used. The isolated lungs (n = 10 in each group) previously being perfused by oxygenated Krebs-Henseleit solution were put in normothermic ischemic conditions. After 3 hours of normothermic ischemia the lungs were reperfused (with Krebs-Henseleit solution in the control group, Krebs-Henseleit solution plus taurine 10−2 M in the experiment group) for 20 minutes. Pulmonary artery pressures, tissue malondialdehyde (MDA) and glutathione (GSH) levels were measured before and after the ischemic period and also at the end of reperfusion. Malondialdehyde and glutathione levels of the pefusate were measured before ischemic period and at the end of reperfusion. An electron microscopic analysis was performed on the lung tissues before and after the ischemic period and also at the end of reperfusion. Decreased pulmonary artery pressure, tissue perfusate MDA levels and increased perfusate GSH levels were observed in taurine added group. Electron microscopic evaluation supported our findings indicating preservation of lamellar bodies of type II pneumocytes. It is concluded that taurine may play an important role in protecting tissue against ischemia-reperfusion injury by functioning as an antioxidant.

Role of free oxygen radicals and prostanoids in the pathogenesis of Henoch-Schönlein Purpura

The pathogenesis of Henoch-Schonlein Purpura (HSP) is still controversial. The aim of our study was to investigate the role of oxidative stress and cyclooxygenase (CO) pathway products in the pathogenesis of HSP. In order to investigate this, malondialdehyde (MDA) levels, indicating lipid peroxidation, prostaglandin E (PGE)-like activity as inflammatory mediator and vitamin E (vit-E) levels indicating anti-oxidant status were studied in a group of 10 children with HSP (five girls and five boys, aged 6-21 years, mean 10.7 years), both in the acute and recovery phase of the disease and in five age and sex-matched healthy children as a control group. The patients were also grouped into low and high clinical score groups. Plasma levels of MDA and PGE-like activity were significantly elevated in the active phase of HSP compared to the recovery phase. Vit-E levels were significantly reduced in the active phase compared to the recovery phase. The plasma levels of PGE-like activity of the patients obtained in the active phase were significantly higher than the levels of the control group, whereas the levels of the recovery phase were significantly lower than in the control group. No such difference between the controls and MDA and vit-E levels in the patient group was shown. No correlation between the clinical scores and the parameters studied could be found. Our findings indicate that oxidant stress and CO pathway products may play a role in the pathogenesis of HSP.

The dose-dependent effects of L-carnitine in myocardial protection in normothermic ischemia

L-Carnitine has been shown to improve the post-ischemic recovery of myocardial function and metabolic measurements that are reduced in the course of ischemia and reperfusion of the heart. In this study we used 40 male guinea-pigs in order to determine if the effect of L-carnitine which is used in the protection of the post-ischemic reperfused heart, is dose-dependent or not. All harvested hearts were perfused for 30 min on modified Langendorf apparatus with oxygenized Krebs-Henseleit solution. After this period, in (n = 10), 5 mmol and 10 mmol (group B, n = 10) of L-carnitine were added into a Krebs-Henseleit solution. After 20 min, perfusion was complete and the hearts were then exposed to normothermic ischemia for 20 minutes. Following the ischemia, hearts were reperfused with the same solutions for 30 min. In group C (n = 10), 10 mmol of L-carnitine was added into the solution at the post-ischemic reperfusion step. In the control group, the same procedures were performed without using L-carnitine. Matching was done according to the contractile force of the heart rate and the levels of malondialdehyde and adenosine deaminase. When 10 mmol L-carnitine was added into the perfusion solutions at the pre-ischemic period, the best results were obtained and myocardial damage was much less than the control group. The protective effects of L-carnitine in normothermic ischemia is dose-dependent and it must be given at the pre-ischemic period.

Biochemical alterations in neonatal hypoxic ischaemic brain damage

Asphyxiated (n = 39) and control (n = 23) were elected for the study. Free radical-mediated lipid peroxidation, prostaglandin E2 and vitamin E levels were studied and the degree of hypoxic ischaemic encephalopathy was determined in each case. In the hypoxic group the concentration of prostaglandin E2 activity (P < 0.05) and malondialdehyde levels (P < 0.01) were significantly higher when compared to that of controls. The high vitamin E concentrations in the asphyxiated infants supports the role of oxygen free radicals in hypoxic ischaemic encephalopathy of newborns.