Investigation of ischemia modified albumin, oxidant and antioxidant markers in acute myocardial infarction.

INTRODUCTION: Acute myocardial infarction (AMI) is still one of the most common causes of death worldwide. In recent years, for diagnosis of myocardial ischemia, a new parameter, called ischemia modified albumin (IMA), which is thought to be more advantageous than common methods, has been researched. AIM: In this study, systematic analysis of parameters considered to be related to myocardial ischemia has been performed, comparing between control and myocardial ischemia groups. MATERIAL AND METHODS: We selected 40 patients with AMI and 25 healthy controls for this study. Ischemia modified albumin levels, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) antioxidant enzyme activities and non-enzymatic antioxidants such as retinol, α-tocopherol, ß-carotene and ascorbic acid levels were investigated in both groups. Glutathione (GSH) and malondialdehyde (MDA) levels, which are indicators of oxidative stress, were compared between patient and control groups. RESULTS: Ischemia modified albumin levels were found significantly higher in the AMI diagnosed group when compared with controls. The MDA level was elevated in the patient group, whereas the GSH level was decreased. SOD, GPx and CAT enzyme levels were decreased in the patient group, where it could be presumed that oxidative stress causes the cardiovascular diseases. CONCLUSIONS: Due to the increased oxidative stress, non-enzymatic and enzymatic antioxidant capacity was affected. Systematic investigation of parameters related to myocardial infarction has been performed, and it is believed that such parameters can contribute to protection and early diagnosis of AMI and understanding the mechanism of development of the disease.

Protective effect of ß-glucan on acute lung injury induced by lipopolysaccharide in rats.

BACKGROUND/AIM: Lipopolysaccharide (LPS)-induced endotoxemia can cause serious organ damage such as acute lung injury and death by triggering the secretion of proinflammatory cytokines and acute-phase reactants. The goal of this study was to evaluate the effects of ß-glucan on inflammatory mediator levels and histopathological changes in LPS-induced endotoxemia. MATERIALS AND METHODS: Forty-seven male Wistar albino rats were randomly allocated into four groups as follows: control group, LPS group (10 mg/kg LPS), LPS + ß-glucan group (100 mg/kg ß-glucan before LPS administration), and ß-glucan group. Twelve hours after LPS administration, lung and serum samples were collected. Concentrations of IL-6, IL-8, C-reactive protein (CRP), and procalcitonin were measured in the serum at hours 0 (basal) and 12. The severity of lung damage was assessed by an appropriate histopathological scoring system. RESULTS: Serum levels of CRP in the LPS group at 12 h were significantly higher than in the other groups, whereas serum IL-6 levels in the LPS and LPS + ß-glucan groups at 12 h were significantly decreased. The mean histopathological damage score of the LPS group was slightly higher than that of the LPS + ß-glucan group. Moreover, mortality rate was significantly decreased in the LPS + ß-glucan group versus the LPS group. CONCLUSION: ß-glucan reduces endotoxemia-induced mortality and might be protective against endotoxemia-induced lung damage.

The effect of Beta glucan on Cisplatin ototoxicity.

This study was undertaken to investigate the effect of betaglucan in ameliorating cisplatin ototoxicity. Rats were divided into four groups: cisplatin (C), cisplatin plus beta glucan (CB), beta glucan (B), and control (K). Distortion product otoacoustic emissions were elicited in 0th, 1st, and 5th days. For the group C differences were observed at 8,003 and 9,515 Hz between 0th and 5th days' measurements. In the group CB there were differences at frequencies of 3,996, 4,757, 5,660, and 6,726 Hz between 0th and 5th days' measurements. For the group B there were significant recovery in some frequencies. The observation of significant deterioration in terms of hearing in the group treated with cisplatin plus betaglucan may be suggested that depended on the increase of permeability and tissue conductance into the inner ear which may be caused by betaglucan. Further long-term follow-up studies by using different doses may clarify this matter.

The effect of lycopene on the ototoxicity induced by cisplatin.

UNLABELLED: Background/aim: To determine the efficacy of lycopene, which is considered an antioxidant agent, in decreasing the cochlear damage induced by cisplatin. MATERIALS AND METHODS: A total of 38 rats were randomized into 4 groups: control, cisplatin, cisplatin + lycopene, and lycopene-treated groups. In all groups, the distortion-product otoacoustic emission measurements were performed on days 0, 1, 2, and 5. RESULTS: There were no significant differences between the control and lycopene groups at any frequencies. In the cisplatin group, the statistically significant differences were found in the measurements taken between day 0 and day 5 at all frequencies and between days 1 and 5 and days 2 and 5 at some frequencies (P < 0.05). In the cisplatin + lycopene group, a statistically significant difference was found at some frequencies between the measurements taken on days 0 and 5, days 1 and 5, and days 2 and 5 (P < 0.05). Contrary to the results found in the cisplatin group, hearing ability in the lycopene-treated group was observed as being preserved at low frequencies in the measurements taken on days 0 and 5 and days 2 and 5. CONCLUSION: The data of this study suggest that lycopene can prevent the development of ototoxicity induced by cisplatin, especially at low frequencies. Studies on this issue with longer durations and different dose ranges may contribute to the identification of potentially prophylactic effects of lycopene against cisplatin ototoxicity at higher frequencies, as well.

Evaluation of the protective effect of Beta glucan on amikacin ototoxicity using distortion product otoacoustic emission measurements in rats.

OBJECTIVES: This experimental study investigated the possible protective effect of beta glucans on amikacin ototoxicity. METHODS: Thirty-eight rats with normal distortion product otoacoustic emissions (DPOAEs) were divided into four groups. Group K was the control group. Group A was injected intramuscularly (i.m.) with amikacin 600 mg/kg/day between days 1-15. Group AB was given beta glucan gavage 1 mg/kg/day on days 0-15 and given amikacin 600 mg/kg/day i.m. on days 1-15. Group B was administered only beta glucan gavage, 1 mg/kg/day, on days 0-15. The DPOAEs were elicited in different frequency regions between 2,003 and 9,515 Hz, as distortion product diagrams (DPgrams), before and after the medication was administered, in all groups, on days 1, 5, 10, and 15. RESULTS: No significant changes in the DPgrams were observed in group K. In group A, significant deterioration was observed at the 8,003 and 9,515 Hz frequencies on day 10, and at the 3,991, 4,557, 5,660, 6,726, 8,003, and 9,515 Hz frequencies on day 15. For group AB, statistically significant deterioration was observed at the 2,824, 8,003, and 9,515 Hz frequencies on day 15. The results for group B showed a significant improvement of hearing at the 2,378, 2,824, 3,363, and 3,991 Hz frequencies on day 1, at the 3,363, 3,991, and 8,003 Hz frequencies on day 10, and at the 8,003 Hz frequency on day 15. CONCLUSION: This study suggests that amikacin-induced hearing loss in rats may be limited to some extent by concomitant use of beta glucan.

Toxic-inflammatory effects of prostoglandin analogs on the ocular surface.

PURPOSE: To investigate the toxic-inflammatory effects of prostaglandin analogs on the ocular surface. MATERIALS AND METHODS: Twenty-three rats were divided into four groups. Bimatoprost 0.03% (I), latanoprost 0.005% (II), and travoprost 0.004% (III) were applied during 6 months; a control group (IV) received no treatment. Dysplasia and keratinization were evaluated on the ocular surface. In the subepithelial area, the number of lymphocytes and mast cells were counted morphologically, and collagen staining densities were compared subjectively in groups. RESULTS: The ratio of keratinization was 3/12 and 1/10, in groups I and II. The lymphocyte cell counts were 1.4 ± 0.19, 2.2 ± 0.39, 2.27 ± 0.33, and 1.87 ± 0.35 (p > .05). The mast cell counts were 2.58 ± 0.5, 5.4 ± 1.1, 5.7 ± 0.58, and 3.0 ± 0.59. They were significantly higher in groups II and III than in group I (p < .05). Mean collagen density scores were 1.00 ± 0.85, 2.00 ± 0.00, and 1,73 ± 0.70. Group II and III scores were higher than group I scores (p < .05). CONCLUSION: Latanoprost and travoprost seem to have more toxic-inflammatory effects on the ocular surface than bimatoprost.

Not only melatonin but also caffeic acid phenethyl ester protects kidneys against aging-related oxidative damage in Sprague Dawley rats.

Microscopic features and antioxidant status of kidneys of young, old, and caffeic acid phenethyl ester (CAPE) and melatonin administered old Sprague Dawley rats were evaluated. Aging-related tubular and glomerular changes were evident. The most prominent tubular alterations were massive vacuole formation, mitochondrial degeneration, and lysosome accumulation. Mean tissue malondialdehyde (MDA) level was increased, mean tissue superoxide dismutase (SOD), catalase (CAT) (p < .001), and glutathione peroxidase (GPx) activities (p < .05), and total glutathione (GSH) level were decreased in old animals. Melatonin significantly reduced tissue MDA levels (p < .005), but increased tissue SOD (p < .001), CAT, and GPx activities (p < .05), and GSH levels (p < .005) in old animals. CAPE also significantly reduced tissue MDA levels (p < .005), but increased tissue SOD (p < .05), CAT (p < .005), GPx activities, and GSH levels (p < .001) in old rats. Mean tissue MDA levels of melatonin and CAPE-administered rats were even lower than those of young rats (p < .05). In conclusion, tubular and glomerular structures and tissue antioxidant enzyme activities were very well preserved in CAPE and melatonin-administered rats.

Melatonin and CAPE are able to prevent the liver from oxidative damage in rats: an ultrastructural and biochemical study.

The liver continuously produces free radicals and reactive oxygen species (ROS) as part of metabolic process. These free radicals are neutralized by an elaborate antioxidant defense system consisting of enzymes and numerous nonenzymatic antioxidants like flavonoids. In this study, we have evaluated effects of melatonin and caffeic acid phenethyl ester (CAPE) to young and aged rat liver. Aging-related hepatic changes examined by light and electron microscopy and biochemical methods. Melatonin and CAPE decreased tissue malondialdehyde (MDA) levels in aged rats. Melatonin elevated tissue glutathione peroxidase (GSH-Px) activity and tGSH level, whereas CAPE elevated tissue catalase activity in aged rats. This study demonstrates that both melatonin and CAPE are beneficial in delaying age-related hepatocellular changes. Melatonin and CAPE supplementation in older ages may support liver to protect itself from various damaging agents including infectious agents and toxins.

Ankaferd blood stopper is more effective than adrenaline plus lidocaine and gelatin foam in the treatment of epistaxis in rabbits.

BACKGROUND: Epistaxis is an important emergency that can sometimes be life threatening without effective intervention. Persistent and recurrent bleeding can lead to aspiration, hypotension, hypoxia, or even severe and mortal cardiovascular complications. Providing prompt hemostasis is important, and the hemostatic method used must be easily and locally applicable, efficient, and inexpensive. OBJECTIVE: The aim of this study was to assess the hemostatic efficacy of Ankaferd Blood Stopper (ABS) in an experimental epistaxis model and to determine the histopathologic alterations with topical ABS application. METHODS: Twenty-eight New Zealand rabbits were evaluated in 4 study groups. Topical ABS, gelatin foam (GF), adrenalin + lidocaine (AL), and serum physiologic as negative control (C) were applied to the animals for controlling epistaxis. The bleeding was generated with a standard mucosal incision in all groups. Cotton pieces soaked with ABS, AL, C, and GF were applied to the nasal bleeding area. Time of hemostasis was recorded. Tissue samples were obtained after hemostasis for histopathologic examination. The samples were stained with hematoxylin and eosin (HE) and phosphotungstic acid hematoxylin (PTAH) and were examined under a light microscope. In this experimental study, the observers were blind to ABS, AL, and C but not to GF, because of its solid nature. RESULTS: Median durations required for hemostasis in ABS, AL, GF, and C groups were recorded as 30, 90, 90, and 210 seconds, respectively. The time until termination of bleeding in the ABS group was significantly shorter than that in the AL, GF, and C groups (P = 0.002, P = 0.002, and P = 0.001, respectively). On histopathologic evaluation, after staining with HE, minimal fibrin at the incision edges and a few extravasated erythrocytes were observed in the C, AL, and GF groups. In the ABS group, a dark amorphous material surrounded by fibrin, filling the space between the edges of incisions, was noticed. Fibrin was determined in the C, GF, and AL groups with PTAH stain and in the positive control group. In the ABS group, it was observed that the amorphous substance surrounded by fibrin seen in the HE sections was not stained with PTAH. CONCLUSIONS: Topical nasal ABS application controlled epistaxis faster than C, GF, and AL in this animal bleeding model. The bleeding model used here might fail to replicate the type of injury that would be likely to result in life-threatening bleeding in humans, which should be considered a limitation of the present study. The histopathologic findings in the nasal incision area suggest that ABS might affect global hemostasis by inducing a unique protein network formation, potentially representing a different mechanism of action among conventional antihemorrhagic applications.

Effects of caffeic acid phenethyl ester on thioacetamide-induced hepatic encephalopathy in rats.

Hepatic encephalopathy (HE) is a major neurological complication secondary to severe liver failure. The aim of the present study was to examine the possible neuroprotective effects of caffeic acid phenethyl ester (CAPE) with or without laxative treatment against thioacetamide-induced HE by investigating behavioral and motor activities in rats as well as blood ammonia level and oxidant-antioxidant parameters of cortex, brain stem and cerebellum. After induction of HE by thioacetamide, the rats were treated with lactulose, CAPE (CAPE treatment was started one day before the first dose of thioacetamide) or CAPE plus lactulose. The behavioral and motor scales were measured at the 54th hour after the first thioacetamide injection, the blood samples and brains were taken under anesthesia at the 60th hour for biochemical analysis. The survival rates were 37.5% in HE group, 70% in HE+lactulose group, 80% in HE+CAPE group, and 100% in HE+CAPE+lactulose group. Increased ammonia, ALT and AST levels in blood along with impaired sensory-motor behavior tests were reversed to proximate control values in CAPE+lactulose treated group. There were increased lipid peroxidation and protein oxidation and decreased antioxidant enzyme activities in almost all brain parts of HE group. CAPE or lactulose treatment alone ameliorated those oxidant and antioxidant parameters; however, CAPE treatment together with lactulose reversed them to almost control level. In conclusion, thioacetamide-induced HE injury in rats was reversed almost fully by CAPE and laxative combination. There was no death in CAPE and laxative treated group animals and it may be due to the direct neuroprotective effect of CAPE together with the prevention of the body from ammonia production.

The protective effect of erdosteine on short-term global brain ischemia/reperfusion injury in rats.

Experimental studies have demonstrated that free radicals play a major role on neuronal injury during ischemia/reperfusion (I/R) in rats. Erdosteine is a thioderivative endowed with mucokinetic, mucolytic and free-radical-scavenging properties. The aim of the present study was to investigate the effect of erdosteine treatment against short-term global brain ischemia/reperfusion injury in rats. The study was carried out on Wistar rats divided into four groups. (i) Control group, (ii) ischemia/reperfusion group, (iii) ischemia/reperfusion+erdosteine group, and (iv) erdosteine group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities as well as thiobarbituric acid reactive substances (TBARSs) and nitric oxide (NO) levels were analysed in erythrocyte and plasma of rats. Plasma NO levels were significantly higher in the ischemia/reperfusion group than the other groups. The activities of SOD and GSH-Px were decreased, while TBARS levels increased in the ischemia/reperfusion group compared to other groups in both plasma and erythrocyte. The erythrocyte CAT activity was higher in erdosteine group and there was a statistically significant increase, when compared with the erdosteine plus ischemia/reperfusion group. By treating the rats with erdosteine, the depletion of endogenous antioxidant enzymes (SOD, CAT, GSH-Px) and increase of TBARS and NO levels were prevented. This study, therefore, suggests that erdosteine reduces parameters of oxidative stress is well supported by the data.

Melatonin treatment against remote organ injury induced by renal ischemia reperfusion injury in diabetes mellitus.

Oxidative stress may have a role in liver damage after acute renal injury due to various reasons such as ischemia reperfusion (IR). Diabetes mellitus (DM) is an important disease for kidneys and may cause nephropathy as a long term complication. The aim of this study was to investigate protective effect of melatonin, a potent antioxidant, against distant organ injury on liver induced by renal IR in rats with or without DM. The rats were divided into six groups: control (n=7), DM (n=5), IR (n=7), DM+IR (n=7), melatonin+IR (Mel+IR) (melatonin, 4 mg/ kg during 15 days) (n=7), and Mel+DM+IR groups (n=7). Diabetes developed 3 days after single i.p. dose of 45 mg/kg streptozotocin. After 15 day, the left renal artery was occluded for 30 min followed 24 h of reperfusion in IR performed groups. DM did not alter oxidative parameters alone in liver tissue. The levels of malondialdehyde, protein carbonyl and nitric oxide with activities of xanthine oxidase and myeloperoxidase were increased in liver tissues of diabetic and non-diabetic IR groups. Nitric oxide level in DM was higher than control. The activities of catalase and superoxide dismutase were increased in IR groups in comparison with control and DM. ALT and AST levels were higher in IR and DM+IR groups than control and DM. Melatonin treatment reversed all these oxidant and antioxidant parameters to control values as well as serum liver enzymes. We concluded that renal IR may affect distant organs such as liver and oxidative stress may play role on this injury, but DM has not an effect on kidney induced distant organ injury via oxidant stress. Also, it was concluded that melatonin treatment may prevent liver oxidant stress induced by distant injury of kidney IR.

Melatonin improves methanol intoxication-induced oxidative liver injury in rats.

This study was performed to evaluate the effect of melatonin on methanol-induced liver injury. We evaluated the levels of malondialdehyde (MDA), protein carbonylation (PC), myeloperoxidase (MPO) activities and to assess lipid peroxidation, protein oxidation, neutrophil accumulation and nitrite which is a stable end product of nitric oxide respectively. We also studied superoxide dismutase, catalase, and glutathione peroxidase activities of liver tissue to evaluate the changes in the antioxidant status. Histopathological alterations were also determined. The experiment was performed on Wistar rats, which received intragastric 3 g/kg methanol as a 50% solution in isotonic saline once. After 6 and 24 hr all the drug received and intoxicated rats were killed under anesthesia. Pretreatment with melatonin (10 mg/kg) decreased the MDA levels significantly, restored the PC levels to the control, prevented the increase of nitrite level and MPO activity significantly and reversed to the control levels, prevented the reduction in all of the antioxidant enzyme activities. Additionally in melatonin treated group piecemeal necrosis, lobular lytic necrosis, and portal inflammation returned to normal histologic appearances when compared with methanol administration. In conclusion, melatonin has protective effects against methanol-induced hepatic injury.

Does pinealectomy affect the recovery rate after spinal cord injury?

Previous reports documented demonstrated that melatonin, a free radical scavenger, is important in protecting against oxidative stress-induced tissue damage after spinal cord injury (SCI). This study was undertaken to investigate the effects of pinealectomy (PX) and administration of exogenous melatonin after SCI in rats. These animals were randomized into six groups, each having 12 rats. Group 1 underwent laminectomy alone. Group 2 underwent laminectomy followed by SCI and received no medication. Group 3 underwent laminectomy followed by SCI and received melatonin. Group 4 underwent PX and laminectomy alone. Group 5 underwent PX and laminectomy followed by SCI and received no medication. Group 6 underwent PX and laminectomy followed by SCI and received melatonin. Melatonin (100 mg/kg) was given intraperitoneally immediately after trauma to the rats in the groups 3 and 6. PX caused a significant increase in the malondialdehyde (MDA), nitrite oxide (NO), glutathione (GSH), xanthine oxidase (XO) levels and decrease in GSH levels as compared with the control group. Trauma to the spinal cord results in significantly higher oxidative stress. Melatonin administration significantly reduced MDA, XO and NO levels, and increased GSH levels in the spinal cord after trauma. Exogenous melatonin treatment after trauma attenuated tissue lesion area and accelerated motor recovery rate. These findings suggest that reduction in endogenous melatonin after PX makes the rats more vulnerable to trauma and exogenous melatonin administration has an important neuroprotective effect on the level of the spinal cord.

Effect of pinealectomy and melatonin replacement on morphological and biochemical recovery after traumatic brain injury.

Numerous studies showed that melatonin, a free radical scavenger, is neuroprotective. In this study, we investigated the effect of pinealectomy and administration of exogenous melatonin on oxidative stress and morphological changes after experimental brain injury. The animals were divided into six groups, each having 12 rats. Group 1 underwent craniotomy alone. Group 2 underwent craniotomy followed by brain trauma and received no medication. Group 3 underwent craniotomy followed by brain trauma and received melatonin. Group 4 underwent pinealectomy and craniotomy alone. Group 5 underwent pinealectomy and craniotomy followed by brain injury and received no medication. Group 6 underwent pinealectomy and craniotomy followed by brain trauma and received melatonin. Melatonin (100 mg/kg) was given intraperitoneally immediately after trauma to the rats in Groups 3 and 6. Pinealectomy caused a significant increase in the malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), and xanthine oxidase (XO) levels, and a decrease in GSH levels as compared to the control group. Trauma to pinealectomized rats causes significantly higher oxidative stress. Exogeneous melatonin administration significantly reduced MDA, XO and NO levels, increased GSH levels, and attenuated tissue lesion area. These findings suggest that reduction in endogenous melatonin after pinealectomy makes the rats more vulnerable to trauma, and exogenous melatonin administration has an important neuroprotective effect.

Hepatic damage in biliary-obstructed rats is ameliorated by leflunomide treatment.

Cholestasis, or impaired bile flow, occurs in a wide variety of liver diseases and causes hepatic damage by retention and accumulation of toxic hydrophobic bile salts inducing persistent inflammation and oxidative stress. In the present research, we studied the effect of leflunomide, a novel immunosuppressive and anti-inflammatory agent against autoimmune disease, on hepatic damage produced by double ligature of the extrahepatic biliary duct in Wistar Albino rats. Cholestasis was done by double ligature and section of the extrahepatic biliary duct (BDL). Leflunomide was given i.g. 10 mg/kg/day. The severity of cholestasis and hepatic injury was determined by changes in the plasma enzyme activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and levels of direct bilirubin. Malondialdehyde (MDA), protein carbonyl (PC), nitric oxide (NO), catalase (CAT) and superoxide dismutase (SOD) were determined to the oxidative status in the liver tissue. Myeloperoxidase (MPO) activity and levels of tissue hydroxyproline (HPR) were determined to neutrophil activation and collagen accumulation, respectively. Further, histological changes were studied. Treatment with leflunomide markedly reduced serum transaminase activities as compared to BDL rats. At the same time leflunomide significantly inhibited increases in liver MDA, PC and NO levels and also attenuated the depletion of CAT and SOD in the liver after bile duct ligation. Similarly, increase in tissue MPO activity and HPR due to BDL was also attenuated by leflunomide treatment. These findings were supported by histopathological findings. These findings suggested that leflunomide can attenuate hepatic damage in extrahepatic cholestasis by prevention of oxidative stress and inflammatory process.

Pentylenetetrazol-induced kindling seizure attenuated by Ginkgo biloba extract (EGb 761) in mice.

Ginkgo biloba extract (EGb 761) has been used therapeutically for centuries. It has attracted great attention as agents for improving circulation, particularly cerebral circulation, which may lead to improved mental function. Many researches hypothesized on the role of the extract in the treatment of diseases involving free radicals and oxidative damage. In the present study, anticonvulsant and antioxidant effects of EGb 761 were investigated in pentylenetetrazol (PTZ)-kindled mice. Valproic acid (VA), a major antiepileptic drug, was also tested for comparison. EGb 761-treated mice displayed a significant attenuated response to PTZ on the test day (day 26) compared with saline-treated and VA-treated animals. Valproic acid significantly increased seizure latency. Pretreatments with EGb 761 significantly protected against PTZ-induced convulsive behaviors (seizure latency, seizure score). EGb 761 and VA significantly decreased PTZ-induced oxidative injury in brain tissue. EGb 761 was found to be the most effective in preventing PTZ-induced oxidative damage among both substances studied. The data obtained support our speculation that neuroprotective action of EGb 761 may correlate with its ability to inhibit not only excessive reactive oxygen species (ROS) formation but also seizure generation. Taken together, the results of the present study show that the effect of EGb 761 on ROS production contributes to their neuroprotective action. It might be concluded that the suppression of seizure-induced ROS generation may be involved in the mechanism of action of antiepileptic drugs.

Protective effects of caffeic acid phenethyl ester on skeletal muscle ischemia-reperfusion injury in rats.

There is a great evidence that reactive oxygen species (ROS) play an important role in the pathophysiology of ischemia-reperfusion (I/R) injury in skeletal muscle. Caffeic acid phenethyl ester (CAPE) is a component of honeybee propolis. It has antioxidant, anti-inflammatory and free radical scavenger properties. The aim of this study is to determine the protective effects of CAPE against I/R injury in respect of protein oxidation, neutrophil in filtration, and the activities of xanthine oxidase (XO) and adenosine deaminase (AD) on an in vivo model of skeletal muscle I/R injury. Rats were divided into three equal groups each consisting of six rats: Sham operation, I/R, and I/R plus CAPE (I/R+CAPE) groups. CAPE was administered intraperitoneally 60 min before the beginning of the reperfusion. At the end of experimental procedure, blood and gastrocnemius muscle tissues were used for biochemical analyses. Tissue protein carbonyl (PC) levels and the activities of XO, myeloperoxidase (MPO) and AD in I/R group were significantly higher than that of control (p < 0.01, p < 0.05, p < 0.01, p < 0.005, respectively). Administration of CAPE significantly decreased tissue PC levels, MPO and XO activities in skeletal muscle compared to I/R group (p < 0.01, p < 0.05, p < 0.05, respectively). In addition, plasma creatine phosphokinase (CPK), XO and AD activities were decreased in I/R+CAPE group compared to I/R group (p < 0.05, p < 0.05, p < 0.001). The results of this study revealed that free radical attacks may play an important role in the pathogenesis of skeletal muscle I/R injury. Also, the potent free radical scavenger compound, CAPE, may have protective potential in this process. Therefore, it can be speculated that CAPE or other antioxidant agents may be useful in the treatment of I/R injury as well as diffused traumatic injury of skeletal muscle.

The effects of ginkgo biloba extract on tissue adenosine deaminase, xanthine oxidase, myeloperoxidase, malondialdehyde, and nitric oxide in cisplatin-induced nephrotoxicity.

This study was carried out to determine if Ginkgo Biloba Extract (GBE or Egb 761) exerts a beneficial effect against cisplatin-induced renal failure in rats. Sprague Dawley rats were divided into four groups. The first group (control) received orally 1 mL/kg/day of 0.9% saline by an oral carrier vehicle on days 1 to 10. The second group was injected with 7 mg/kg cisplatin intraperitoneally (i.p.) on the fourth day, once only. The third group (vit E+cisplatin) was administered 10 mg/kg/day i.p. vit E on 1 to 10 days with one dose of i.p. cisplatin (7 mg/kg) injection on the fourth day. The fourth group (GBE+cisplatin) was given GBE orally at 100 mg/mL/kg started on the first day up to the tenth day with one dose of cisplatin (7 mg/kg) injection on the fourth day. Cisplatin was found to lead a statistically significant increase in plasma BUN and creatinine levels, as well as urine micro total protein (MTP) levels, leading to acute renal failure (ARF) in rats. Renal xanthine oxidase (XO) activities increased in all groups (statistically significant in cisplatin + GBE-treated rats; P < 0.001). Adenosine deaminase (AD) activities were increased in cisplatin-treated rats, and decreased in cisplatin+GBE-treated (P < 0.041) and cisplatin+vit E-treated (P < 0.005) rats, compared to controls. Malondialdehyde (MDA), nitric oxide (NO) levels and myeloperoxidase (MPO) activities were increased in the kidney tissue of cisplatin-treated rats. Vit E improved plasma creatinine and urine MTP levels, together with tissue MDA, NO levels, and MPO activities. But GBE had no statistically significant effect on those parameters. These results indicate that increased XO, AD and MPO activities, as well as MDA and NO levels play a critical role in cisplatin nephrotoxicity. GBE has been shown to protect against cisplatin-induced nephrotoxicity.

Effects of Ginkgo biloba on plasma oxidant injury induced by bleomycin in rats.

Bleomycin is an anti-neoplastic agent and its clinical usage is limited by its toxicity, which is mostly induced by oxygen radicals. The aim of this study was to investigate the effect of Ginkgo biloba on plasma indices of oxidants induced by bleomycin in rats. Male Sprague-Dawley rats were divided into five groups: none medicated or 0.9% NaCl injected or only Ginkgo biloba (orally, 100 mg/kg per day for 14 days) or only a single dose of bleomycin (intratracheal, 2.5 U/kg) or Gingko biloba and bleomycin-treated groups. After 14 days, blood was taken before the rats were sacrificed. The plasma was removed and stored at -85 degrees C until the study day. Plasma superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) enzyme activities with malondialdehyde and nitric oxide (NO) levels were studied. The levels of malondialdehyde and NO with activity of XO were higher in plasma of bleomycin group than the other groups (P <0.05). The activities of SOD and GSH-Px were increased in the bleomycin plus Gingko biloba group in comparison with the bleomycin group (P <0.05). There was a positive correlation between malondialdehyde and NO levels in the bleomycin group (r =0.859, P <0.05). There were positive correlations between SOD and GSH-Px activities (r =0.760, P <0.05) and between XO activity and malondialdehyde level (r =0.822, P <0.05) in the bleomycin plus Gingko biloba group. In conclusion, it was thought that bleomycin induced oxidative stress can be prevented by Gingko biloba treatment via high anti-oxidant enzyme activity together with decreased radical production from XO.