Protective effect of N-acetylcysteine, caffeic acid and vitamin E on doxorubicin hepatotoxicity.

The aim of this study was to compare the possible protective effects of N-acetylcysteine (NAC), caffeic acid (CAPE) and vitamin E (Vit-E) on doxorubicin-induced hepatotoxicity. Thirty-two male Wistar albino rats, weighing between 250 and 350 g were supplied and randomly divided into five groups. Animals in study groups were pretreated with a single dose of doxorubicin (Dox), which was administered intraperitoneally (i.p.). Control group (Group I) was treated with intraperitoneal saline injection. Group II did not received any antioxidant agent after the injection. Group III and Group IV were given CAPE and intraperitoneal vitamin E injection for eight days, respectively. Group V received NAC for eight days. The study was finished after 10 days. Tissue samples were collected from all animals and histopathological examination was performed. There was statistically significant difference between the experiment groups and controls by means of mononuclear cell infiltration and diameters of hepatic sinusoid, terminal hepatic venule (central vein) and portal area (portal canal). Changes related with hepatocellular damage were more prominent, whereas there was no significant difference between Dox and NAC given groups histopathologically. It was observed that structural changes were regressed after CAPE administration. However, this recovery was more prominent in vitamin E given group. These findings suggest that Dox induced liver damage could be efficiently reversed by vitamin E administration. It has been found that CAPE, but not NAC has protective effects on Dox-induced hepatocellular damage.

Effect of melatonin against oxidative stress in ultraviolet-B exposed rat lens.

PURPOSE: To investigate the defensive effect of melatonin against oxidative stresses in ultraviolet-B (UVB) radiation induced cataract development. METHODS: Young rats received 8 kJ/m(2) UVB for 15 min. For the intervention of cataract development intraperitoneal injection of melatonin (4 mg/kg daily for 1 week) following UVB exposure was performed. Lenticular glutathione peroxidase (GSHPx), catalase (CAT), superoxide dismutase (SOD) activities and glutathione (GSH), malondialdehyde (MDA) levels were determined in UVB-melatonin, UVB, and control groups. RESULTS: One week after exposure in the UVB group, lens opacities were observed and CAT, SOD, and GSHPx activities, and GSH level were lower than control and MDA level was higher than control (p < 0.05). In the UVB-melatonin group CAT and SOD activities were lower than control (p < 0.05), and the MDA level was lower than the UVB group (p < 0.05). CONCLUSIONS: These results suggest that melatonin may protect against the UVB-induced cataract development by directly quenching lipid peroxides and indirectly by enhancing the production of the endogenous antioxidant GSH.

Pentoxifylline inhibits overflow and reduces intestinal reperfusion injury.

The aim of this study was to determine the effects of pentoxifylline (Ptx) in reperfusion injury of the small bowel as a leukocyte stabilizer, free radical scavenger, and microcirculatory regulator. Ninety-six male Sprague-Dawley rats were used to determine the biochemical, histopathologic and blood flow changes of the reperfused small intestines after 30 minutes of a warm ischemic insult. Animals were divided into six groups: Sham (S), sham plus Ptx (SP), ischemia (I), ischemia plus Ptx (IP), reperfusion (R), and reperfusion plus Ptx (RP). Pentoxifylline was administered intraperitoneally at a dose of 50 mg/kg 15 minutes before ischemia. The superior mesenteric artery (SMA) was occluded distal to the right colic artery and collateral arcades were ligated as described by Megison. Sixty of the 96 rats (n = 10) were used to determine histopathologic changes, malondialdehyde (MDA), and myeloperoxidase (MPO) levels in tissue. Mucosal lesions were graded on a scale from 0 to 5 as described by Chiu. MDA and MPO levels of the intestinal mucosa were assayed to reflect the free radical formation and neutrophil sequestration, respectively. Thirty-six rats (n = 6) were used to measure blood flow changes of the intestine using 133Xe clearance technique. All data were presented as the mean values plus or minus the standard error of the means (means +/- sem). Although in the R group, mucosal injury score, blood flow, MPO, and MDA levels were higher significantly from the other groups (P < .05), in the RP group blood flow, MPO, and MDA levels were significantly decreased to the basal values (P < .05). Mucosal injury score of the RP group were lower than the reperfusion group but higher than the normal (P < .05). The authors conclude that pentoxifylline pretreatment before reperfusion stabilizes blood flow, decreases MPO and MDA levels to the normal, and attenuates but not completely prevents mucosal damage.

Activity of factor VIIa and von Willebrand factor in non-insulin-dependent diabetic subjects with coronary artery disease.

Atherosclerosis is more extensive and occurs earlier in diabetics compared with the general population. The pathophysiology of atherosclerosis is not fully established. We compared the activity of two blood clotting agents, activated factor VII (VIIa) and von Willebrand factor (vWF), in diabetic and non-diabetic subjects with coronary artery disease. According to clinical features, subjects were placed in one of four groups: Group I, non-insulin-dependent diabetes mellitus (NIDDM) with coronary heart disease (CAD) (n = 16); Group II, NIDDM (n = 15); Group III, CAD with no presence of diabetes (n = 17); and Group IV, healthy volunteers (n = 15). The level of factor VIIa was higher in Group I compared with all other groups, and was significantly higher in Group II compared with Group III and Group IV. Activity of vWF was higher in Group I compared with Group II, Group III and Group IV. There was no statistical difference between Group II and Group III. There was no significant correlation between concentration of blood glucose, total cholesterol or triglyceride, duration of diabetes and either factor VIIa or vWF activity. The results of this study suggest that increased activity of plasma vWF and factor VIIa may be useful markers to identify ischaemic heart disease risk in NIDDM subjects.

Lipid peroxidation and glutathione peroxidase activity in chronic obstructive pulmonary disease exacerbation: prognostic value of malondialdehyde.

Results of recent studies have indicated that during exacerbation of chronic obstructive pulmonary disease (COPD), antioxidant capacity is lower and the levels of lipid peroxidation products are higher than those in age-matched healthy subjects. The aim of this study was to assess the time course of changes in oxidant stress during the treatment of exacerbation of COPD. For this purpose, we measured erythrocyte glutathione peroxidase (GPx) activity and serum levels of the lipid peroxidation product malondialdehyde (MDA) in 18 male patients with acute exacerbation of COPD. Fifteen healthy non-smokers having no history of lung disease served as control subjects. Mean erythrocyte GPx values of patients were 45.54 +/- 9.04 u/gHb on admission and had increased to 72.77 +/- 9.68 by the tenth day of treatment, but still remained lower than those of healthy subjects (83.13 +/- 10.91) (p=0.007). Serum MDA values in patients were Vol. 12, No. 1, 2001 significantly higher (2.68 +/- 1.28 nmol/ml) than those in control subjects (1.04 +/- 0.36 nmol/ml) (p=0.000) and returned to normal values by the tenth day of treatment (1.08 +/- 0.36 nmol/ml) (p=0.766). Erythrocyte GPx values in patients who were current smokers (39.87 +/- 3.82 u/gHb) were lower than those in ex-smokers (49.15 +/- 9.67 u/gHb) (p=0.021). Moreover, serum MDA values in patients who were current smokers (3.32 +/- 1.18 nmol/ml) were higher than those in ex-smokers (1.66 +/- 0.60 nmol/ml) (p=0.007). The results show that oxidative stress in patients with acute exacerbation of COPD is related to higher MDA levels that return to normal conditions during the course of treatment. In conclusion, the results suggest that MDA levels can serve as a marker of prognosis and of the success of treatment of the exacerbation of COPD.

Splenectomy reduces remote organ damage after intestinal ischaemia-reperfusion injury.

PURPOSE: In this study, we aimed to reduce mononuclear phagocytic system (MFS) cells with splenectomy and investigate its preventive effects on lung, liver, and kidney ultrastructure and free radical generation after intestinal ischaemia-reperfusion (IIR). METHOD: Forty adult male albino Wistar rats were randomly divided into four groups as sham laparatomy (SL), splenectomy + sham laparatomy (SSL), intestinal ischaemia-reperfusion (IIR), and splenectomy + intestinal ischaemia-reperfusion (SIIR). One hour of mesenteric ischaemia and four hours of reperfusion were applied. Splenectomy was performed just before reperfusing the intestine. Serum levels of malonedialdehyde (MDA) was measured, and tissue samples obtained from the lung, liver, and kidneys were fixed in 2.5% glutaraldehyde for electron microscopy. RESULTS: Lung, liver, and kidney ultrastructures were normal in both groups of SL and SSL. In the IIR group, type 2 pneumocytes showed lamellar body degeneration, dilation of smooth endoplasmic reticulum, and thickening of the basal lamina. Hepatocytes showed dilation of the rough endoplasmic reticulum, mitochondrial degeneration, and cytoplasmic lipid droplets. The glomerular basement membrane was thickened and the endothelial cells showed discontinuity. The foot processes of the podocytes and microvilli of the proximal tubule cells had also disappeared in the kidney. Splenectomy attenuated these ultrastructural changes in the SIIR group. In the IIR group, serum MDA level was significantly increased to 171.7 +/- 6.7 nmol/ml (p < 0.05). Splenectomy significantly reduced serum MDA level to 87.8 +/- 2.5 nmol/ml in the SIIR group (p < 0.05). CONCLUSIONS: Splenectomy attenuated degenerative findings encountered in lung, liver, and kidney ultrastructure after IIR. Splenectomy also significantly decreased serum levels of MDA. The possible role of splenectomy is to reduce the MFS cells, which play an important role in the remote organ injury after intestinal reperfusion damage.

The protective effect of caffeic acid phenethyl ester (CAPE) on oxidative stress in rat liver exposed to the 900 MHz electromagnetic field.

In this study, we aimed to investigate the possible protective effects of caffeic acid phenethyl ester (CAPE) on lipid peroxidation (LPO) and the activities of antioxidant enzymes in the liver of rats exposed to the 900 MHz electromagnetic field (EMF). EMF of cellular phones may affect biological systems by increasing free radical, which appear mainly to enhance LPO, and by changing the antioxidative activities of liver, thus leading to oxidative damage. CAPE, an active component of propolis extract, exhibits antioxidant properties and several studies suggest that supplementation with antioxidant can influence EMF exposure induced hepatotoxicity. Thirty male Sprague-Dawley rats were divided into three groups: control (n = 10), 900 MHz EMF (n = 10) and 900 MHz EMF + CAPE (n = 10). CAPE was injected intraperitoneally for 30 days before exposure to EMF. Liver tissue was removed to study the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), xanthine oxidase (XO) and the levels of LPO. The activities of XO, CAT and level of LPO increased in the 900 MHz electromagnetic field (EMF) group compared with the control group, although XO, CAT activities and LPO levels were decreased by 900 MHz EMF + CAPE administration. The activities of SOD and GSH-Px decreased in the 900 MHz EMF group compared with the control group, although their levels were increased by EMF + CAPE administration. It can be concluded that CAPE may prevent the 900 MHz EMF-induced oxidative changes in liver by strengthening the antioxidant defense system by reducing reactive oxygen species and increasing antioxidant enzyme activities.

Melatonin levels and enzymatic antioxidant defense system decrease in blood of patients with bronchial asthma.

The etiology of bronchial asthma (BA) is not clearly understood. In recent years, a few studies have investigated the possible role of reactive oxygen species (ROS) in the etiology of BA. There are some defense mechanisms in the organism to avoid the harmful effects of ROS. Melatonin (MEL) is synthesized by the pineal gland at night and exhibits antioxidant properties. The aim of this study was to investigate serum MEL levels, erythrocyte antioxidant enzyme activities, namely superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the association of the respiratory function tests, namely dynamic lung volumes; the forced vital capacity (FVC/L, FVC%), the forced expiratory volume in 1 s (FEV(1)/L, FEV(1)%), and peak expiratory flow (PEF/L/s, PEF%) in 30 patients with BA and 30 age-matched healthy controls. The levels of serum MEL, the activities of erythrocyte SOD, and the values of FVC/L, FVC%, FEV(1)/L, and FEV(1)% were significantly lower in the patients with BA than in control group. The positive correlations were observed between FVC% with erythrocyte SOD and GSH-Px, FEV(1)/L as well as FEV(1)% with erythrocyte SOD, whereas negative correlation was observed between PEF/L/s with levels of serum MEL. In conclusion, these results provide some evidence for a potential role of decreased antioxidant enzymes, MEL, and respiratory function test values in BA.

The effect of melatonin application on lipid peroxidation during cyclophosphamide therapy in female rats.

OBJECTIVE: Our purpose was to investigate whether melatonin has any protective effect against lipid peroxidation induced by cyclophosphamide. MATERIAL AND METHODS: We used an animal model to study the effect of melatonin. Fifteen female Wistar rats (180-200 gram in weight) were randomly assigned to three different groups. Group 1 (n = 5) received saline injections as a control. Group 2 (n = 5) received cyclophosphamide. Group 3 (n = 5) received cyclophosphamide + melatonin. The animals were sacrificed two hours after cyclophosphamide administration and blood samples were taken and used for assaying superoxide dismutase (SOD) activity, glutathione peroxidase (GP) activity for the antioxidative enzymes, and malondialdehyde (MDA) level as an index of lipid peroxidation. RESULTS: MDA levels were more increased in the second group compared with the control group (p < 0.01). In the third group, they were significantly lower than in the second group (p < 0.05). SOD and GP activities were found to be decreased significantly in the second group compared with the control group (p < 0.05 and p < 0.01, respectively). They were found to be elevated in the third group compared with the second group (p > 0.05 and p < 0.05, respectively). CONCLUSIONS: The above results suggest that melatonin has a protective role in cyclophosphamide induced lipid peroxidation in rats. Besides scavenging the highly toxic free radicals, melatonin also stimulates the antioxidant enzyme activity of GP.