Nilüfer Erkasap

The antioxidative and antihistaminic properties of quercetin in ethanol-induced gastric lesions

The role of reactive oxygen species in the pathogenesis of acute ethanol-induced gastric mucosal lesions and the effects of quercetin were evaluated in an experimental model. In addition, the effects of quercetin on gastric damage were evaluated histopathologically. Rats were divided into three groups as control rats, ethanol treated rats and ethanol+quercetin treated rats. Ethanol group was given a gastric gavage containing 1 ml of 80% ethanol (v/v) prepared in distilled water. Quercetin (200 mg/kg body wt.) was given by intragastric gavage 120 min before the administration of ethanol. Gastric tissue thiobarbituric acid reactive substance levels, carbonyl compounds, histamine levels and myeloperoxidase activities were found to be increased in ethanol treated rats and quercetin treatment reversed these increases. No statistically significant changes were found between all groups in catalase activity. The superoxide dismutase activity dropped significantly after ethanol treatment and quercetin treatment increased this enzyme activity. Gastric damage was confirmed histomorphometrically by significant increases in the number of mast cells and gastric erosions in ethanol treated rats. It was also confirmed that quercetin treatment significantly decreased the number of mast cells and reduced the area of gastric erosions. The results suggest that the gastroprotective effect of quercetin in this experimental model could be due to its antiperoxidative, antioxidant and antihistaminic effects.

Effects of carvacrol on defects of ischemia-reperfusion in the rat liver.

Many plants found in nature have been used to treat various illnesses. One such plant is oregano (Kekik in Turkish). Health beneficial effects of carvacrol obtained from oregano oil have been shown scientifically. We have investigated the comparative effects of carvacrol in the liver of rats subjected to ischemia-reperfusion defect, with silymarin. To test the effects we formed four groups using male Wistar albino rats. Group I was control. The other three groups of animals were administered 60min prior to surgical operation single doses of physiological serum, carvacrol and silymarin, respectively. Group II, III and IV animal were subjected to 45min long liver ischemia and 60min reperfusion. Blood and tissue samples were collected for biochemical and histological analysis following the test. AST and ALT values obtained after biochemical analysis of the serums showed statistically significant difference in group II than the other three groups. A statistical evaluation of the serum AST levels among the groups II, III and IV showed that both groups III and IV which had no difference in between were significantly different in a positive way from group II (p<0.001). As to the serum ALT levels, difference between group II and group III (p<0.001) and group II and group IV (p<0.01) was found significant. No statistical difference was observed in groups I, III and IV for GSH, MDA and CAT levels of the liver. A statistical evaluation of the GSH level in group III and group IV was found to be significantly different from group II (p<0.001) without any difference between them. A similar evaluation for MDA and CAT levels among the revealed no difference between group III and group IV, however, group II showed difference with group II and group IV (p<0.05). Histological findings were in harmony with the biochemical results. We conclude that carvacrol protects the liver against defects caused by ischemia and reperfusion, and carvacrol is not hepatotoxic at the applied dosage.

Cardioprotection with resveratrol pretreatment: improved beneficial effects over standard treatment in rat hearts after global ischemia

Objective—The major objective of the present study is to evaluate the potential role of resveratrol (RVT), a natural antioxidant found in grapes and red wine, in protecting the myocardium from the deleterious effects of ischemia‐reperfusion (I/R) injury using isolated rat hearts. Methods—Langendorff perfused isolated rat hearts were subjected to 60 min of global ischemia following 60 min of reperfusion. RVT was given according to chronic pretreatment and/or acute treatment protocols. Animals received RVT at the dose of 20 mg/kg via an intragastric tube for 14 days before the experiment and/or at the infusion concentration of 10 μM for 30 min before the onset of ischemia. The myocardial postischemic recovery was compared using hemodynamic data (peak systolic pressure, end diastolic pressure, and +dP/dt max ), coronary flow, biochemical parameters (LDH, CK‐MB, cTnI, myoglobin) from coronary effluent, and oxidative stress markers (MDA, GSH, carbonyl) from heart tissue homogenates in each group. Results—RVT pretreatment and treatment protocols have provided increased preservation in myocardial recovery following global ischemia compared to a non‐treated group. Furthermore, the ischemic damage of myocardium was significantly lower in chronic pretreated rats than in the acutely treated group. In contrast, no significant difference was observed in cardioprotective effects of RVT between the only pretreated group, and both the pretreated and treated group throughout reperfusion. Conclusion—The findings from this study indicate that RVT has potent cardioprotective properties against I/R injury in rat hearts. The study also highlighted that the administration of RVT, as pretreatment, has amplified the beneficial effects over the standard treatment.

Gastroprotective effect of leptin on gastric mucosal injury induced by ischemia-reperfusion is related to gastric histamine content in rats.

Leptin has cytoprotective effect to gastric mucosal injury in rats. We aimed to test the hypothesis that leptin induced histamine is involved in the prevention of ischemia-reperfusion (I/R) induced gastric mucosal injury in rats. At the end of the 30 min celiac artery occlusion and 12h reperfusion process, serum and gastric tissue samples were taken from three group of rats to measure oxidative status, histamine levels and for histological examinations. Leptin decreased ulcer and polymorphonuclear leukocyte (PMNL) index, and serum malondialdehyde (MDA) and protein carbonyl content but increased gastric tissue histamine levels. We concluded that leptin exerts a protective effect on gastric mucosa to I/R induced gastric injury probably through increasing tissue histamine content which, in turn, maintain the gastric mucosal blood flow.

Effects of tramadol on myocardial ischemia-reperfusion injury

Objectives. The aim of the present study was to evaluate the effect of tramadol on isolated rat hearts subjected to global ischemia-reperfusion injury. Design. Langerdorff perfused isolated rat hearts were subjected to 60 min of global ischemia following 60 min of reperfusion. In group I and III hearts were received tramadol before the onset of ischemia. Following the ischemic period, group II and III hearts were received tramadol infusion. Group I and IV hearts were subjected to saline at the same time point. The myocardial postischemic recovery was compared using hemodynamic, coronary flow, biochemical parameters from coronary effluent, and oxidative stress markers from heart tissue homogenates. Results. There were significant differences between tramadol and saline used groups in hemodynamic parameters. GPx values of groups I and III were significantly lower than group IV (p<0.05). SOD values of groups I, II and III were higher than group IV (p<0.05). LDH values of groups I and II were significantly lower than groups III and IV (p<0.05). Conclusion. Tramadol provides a cardioprotective effect against myocardial ischemia-reperfusion in isolated rat heart.

Effect of leptin on renal ischemia-reperfusion damage in rats

Tumor necrosis factor-alfa (TNF-α) has been established as an important mediator in renal ischemia-reperfusion (I/R) injury. Leptin, a product of the ob gene, has been known to exhibit cytoprotective effects on renal tissue, but its effect on renal tissue TNF-α level after renal I/R injury in rats remains unknown. The purpose of the study was to evaluate the effects of leptin on renal tissue TNF-α, malondialdehyde (MDA), protein carbonyls (PCs) and total sulfydryl group (SH) levels, and plasma nitrite levels after renal I/R injury in rats. The animals were divided into three groups: control, I/R and I/R+leptin. Rats were subjected to renal ischemia by clamping the left pedicle for 45 min, and then reperfused for 1 h. The I/R+leptin group was pretreated intraperitoneally with leptin (10 μg/kg) 30 min before the induction of ischemia. Our results indicate that MDA, TNF-α levels, and PCs were significantly higher in the I/R group than those in the control group (p<0.05). The administration of leptin decreased these parameters (p<0.05) significantly. The SH level was observed to significantly decrease after I/R injury when compared to the control group (p<0.05). Leptin treatment significantly increased tissue SH and plasma nitrite levels when compared to the I/R group (p<0.05). Plasma nitrite levels did not change significantly in I/R when compared to the control. These results suggest that leptin could exert a protective effect on I/R induced renal damage by decreasing TNF-α levels and increasing nitrite level.ResumenEl factor de necrosis tumoral alfa (TNF-α) está implicado en la lesión renal tras isquemia y reperfusión (I/R). Dado que se ha observado que la leptina presenta un efecto citoprotector sobre el tejido renal, se estudia en este trabajo el efecto de la hormona sobre el contenido en el tejido renal de TNF-α, malondialdehido (MDA), niveles de grupos carbonilo protéicos (PC) y de los grupos sulfhidrilo total (SH), y el nivel plasmático de nitrito tras lesión renal por isquemia/reperfusión en rata. Los animales se repartían en tres grupos de 8 ejemplares: control, I/R, e I/R+leptina. Las ratas se sometían a una isquemia renal durante 45 minutos con ulterior reperfusión de una hora. A los del grupo I/R+leptina se les había administrado por vía intraperitoneal leptina (10 μg/kg) 30 minutos antes de la inducción de la isquemia. Los resultados indican que el contenido en MDA, TNF-α y PC está significativamente elevado en el grupo I/R respecto del grupo de control (p<0.05), mientras que el de SH se reduce tras la lesión I/R y el nivel de nitrito en el plasma no varía. El tratamiento con leptina anula los incrementos de los niveles renales de TNF-α, MDA y PC y de la disminución de grupos SH en tejido renal e incrementa el nivel de nitritos plasmáticos por isquemia/reperfusión renal. Estos resultados sugieren que la leptina ejerce un efecto protector sobre la lesión renal inducida por isquemia y reperfusión por la disminución de TNF-α y el aumento plasmático de nitrito.

Effects of Doxycycline on Renal Ischemia Reperfusion Injury Induced by Abdominal Compartment Syndrome

BACKGROUND The aim of this study was to determine the effects of doxycycline on renal ischemia reperfusion (I/R) injury in a rat model of abdominal compartment syndrome (ACS). MATERIALS AND METHODS Forty-two Sprague-Dawley rats were divided into six groups. In the control group (group 1), kidney samples were collected with no manipulation; in the sham group (group 2) induction of ACS was followed by decompression. In groups 3 and 4, 1 cc of saline was administered intraperitoneally (i.p.) during the induction of ACS, and the kidneys were removed 1 and 24h after decompression, respectively. In groups 5 and 6, doxycycline (10mg/kg i.p.) was injected during the induction of ACS, and similarly all tissue samples were removed 1 and 24h after decompression, respectively. MDA, IL-1β, IL-6, TNF-α, MMP-2, and TIMP-1 were studied, and the apoptotic cells were enumerated histopathologically, and apoptosis and bcl-2 expression were assessed immunohistochemically. RESULTS Creatinine, MDA, IL-1β, and IL-6 levels were significantly higher in group 3, 1h after the reperfusion period compared with the control group, and the same parameters were significantly lower in the groups in which doxycycline was administered, 1 hour after decompression. However, there remained no difference between groups at 24h, except IL-1β, which was decreased to even lower values. TNF-α and TIMP-1 levels were not statistically different in all groups. The MMP-2 level was significantly higher in group 4 by 24h, and there remained no difference between groups 1, 2, and 6. In group 6, there were not any apoptotic cells as were observed in the other groups. The number of apoptotic cells and the expression of bcl-2 was significantly less in the groups in which doxycycline was administered. CONCLUSION Doxycycline had protective effects on I/R injury by decreasing apoptosis via reducing the level of pro-inflammatory cytokines, increasing the level of TIMP-1, and inhibiting the activity of MMP-2.

Protective effects of doxycycline in ischemia/reperfusion injury on kidney

Renal ischemia and reperfusion injury is the major cause of acute renal failure and may also be involved in the development and progression of some forms of chronic kidney disease. The aim of this study was to evaluate whether doxycycline, a member of the tetracycline family of antibiotics, protects kidney tissue or not. 36 Sprague-Dawley rats (200–250 g) were used. The animals were divided into three groups: control, ischemia/reperfusion and ischemia/reperfusion+doxycycline group. Rats were subjected to renal ischemia by clamping the left pedicle for 1 h, and then reperfused for 1 h. The ischemia/reperfusion+doxycycline group were pretreated intraperitoneally with doxycycline suspension (10 mg/kg) 2 h before the induction of ischemia. Our results indicate that malondialdehyde, matrix-metalloproteinase-2, interleukin-2, interleukin-6, interleukin-10, interleukin 1-beta and tumor necrosis factor-alpha levels were significantly higher in the ischemia/reperfusion group than those in the control group. Doxycycline administration significantly decreased these parameters. Tissue inhibitor of metalloproteinases-1 levels also increased after ischemia/reperfusion and decreased with doxycycline pretreatment, but these changes were not significantly different. Glutathione levels significantly decreased after ischemia/reperfusion injury when compared with the control group and doxycycline pretreatment significantly increased glutathione levels when compared with the ischemia/reperfusion group. Apoptotic cells and p53 positive cells were significantly decreased in doxycycline treated group. These results suggest that doxycycline reduces renal oxidative injury and facilitates repair. Doxycycline may play a role in a renoprotective therapeutic regimen.

Protective Effects of Leptin on Ischemia/Reperfusion Injury in Rat Bladder

The aim of the study was to evaluate protective effects of exogenous leptin on ischemia/reperfusion (I/R)-induced injuries to the urinary bladder tissue and to investigate the effect on tumor necrosis factor alpha (TNF-alpha) levels and apoptotic cells during I/R injury. Bladder I/R injury was induced by abdominal aorta occlusion by ischemia for 45 min, followed by 60 min of reperfusion in rats. The rats were divided into three groups: control (n = 8 + 8), I/R (n = 8 + 8) and I/R+leptin group (n = 8 + 8). The rats in the I/R+leptin group were treated intraperitoneally with leptin (10 microg/kg) 60 min prior to ischemia induction. At the end of the reperfusion period, urinary bladders of the first eight rats from each group were removed for TUNEL staining processing while the others were removed for biochemical analyses for MDA and TNF-alpha levels. In the I/R group, the ratios of TUNEL-positive nuclei were higher than the control and the I/R+leptin groups. The MDA and TNF-alpha levels of the bladder tissue in the I/R group were higher than the control and leptin-treated groups. TUNEL-staining and biochemical studies revealed that leptin has a protective effect on urinary bladder I/R injury.

Protective effect of chitosan treatment against acetaminophen-induced hepatotoxicity

Acetaminophen (APAP) is the most commonly reported toxic ingestion in the world. Severe liver injury resulting from overdose or chronic use of APAP remains a significant clinical problem. In recent years, the mechanisms underlying liver injury caused by APAP have become much better understood. We have studied the protective effect of chitosan supplementation against APAP‐induced hepatotoxicity with respect to changes in the levels of total and lipid‐bound sialic acid in the serum and in the liver tissue and changes in the activity of diagnostic marker enzymes, lipid peroxidation, and ceruloplasmin oxidase enzyme in normal and experimental groups of rats. During the experimental period, chitosan (200 mg/kg body weight per day) was administered to APAP + chitosan‐treated rats by oral gavage. Results showed that treatment with APAP induced a significant increase in the serum alanine aminotransferase and alkaline phosphatase activities, in total and lipid‐bound sialic acids levels, and in the liver lipid peroxide content. The administration of chitosan significantly prevented APAP‐induced alterations in the levels of diagnostic marker enzymes, total sialic acid, lipid‐bound sialic acid, and malondialdehyde in the experimental groups of rats. Furthermore, chitosan administration increased the activity of ceruloplasmin oxidase. In conclusion, our results suggest that chitosan has a protective effect on APAP‐induced hepatic injury in rats. The study sheds light on the therapeutic potential of chitosan in an APAP‐induced hepatotoxicity model.