Search

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.

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.

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., (Copyright © 2010 Elsevier Inc. All rights reserved.)

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.

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer. High doses of cisplatin have also been known to produce hepatotoxicity. Several studies suggest that supplementation with an antioxidant can influence cisplatin-induced hepatotoxicity. The present study was designed to determine the effects of cisplatin on the liver oxidant/antioxidant system, and the possible protective effects of caffeic acid phenethyl ester (CAPE) on liver toxicity induced by cisplatin. Twenty-four adult female Wistar albino rats were divided into four groups of six rats each: control, cisplatin, CAPE, and cisplatin+CAPE. Cisplatin and CAPE were injected intraperitoneally. Liver tissue was removed to study the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), xanthine oxidase (XO), adenosine deaminase (ADA), and the levels of malondialdehyde and nitric oxide (NO). The activities of SOD and GSH-Px increased in the cisplatin+CAPE and CAPE groups compared with the cisplatin group. CAT activity was higher in the cisplatin +CAPE group than the other three groups. XO activity was lower in the cisplatin group than the control group. MPO activity was also increased in the cisplatin group compared to the control and CAPE groups. It can be concluded that CAPE may prevent cisplatin-induced oxidative changes in liver by strengthening the antioxidant defence system by reducing reactive oxygen species and increasing antioxidant enzyme activities., (Copyright (c) 2006 John Wiley & Sons, Ltd.)

Oxygen-derived free radicals have been implicated in the pathogenesis of tissue injury after ischaemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active ingredient of honeybee propolis, has been identified as having potent antioxidant and anti-inflammatory properties. We evaluated the ability of CAPE applied intraperitoneally in reducing tissue injury after ischaemia-reperfusion. To investigate whether treatment with CAPE modifies the concentrations of the endogenous indices of oxidant stress, we examined its effects on a model of flap ischaemia-reperfusion injury in rats. CAPE (10 micromol/kg) was given through the peritoneum before reperfusion. CAPE given intraperitoneally had an inhibitory effect on tissue injury after ischaemia-reperfusion comparable to that of a control group. The anti-inflammatory and antioxidant properties of CAPE may contribute to its suppression of tissue injury.

Since overexcitation of excitatory amino acid is an important mechanism in seizure genesis wherein free radicals have recently been suggested to play a critical role, we explored the effects of caffeic acid phenethyl ester (CAPE) administration in pentylenetetrazole (PTZ)-induced seizure in mice. CAPE prevents the oxidative damage in brain tissue induced by PTZ, scavenging reactive oxygen species (ROS). Our results demonstrate that CAPE treatment which prevents free radical production and ameliorates seizure severity may be useful at least as an adjunctive treatment of seizure disorders.

Background: Nephrotoxicity is one of the important side effects of antracycline antibiotics. The aim of this study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, against nephrotoxicity induced by doxorubicin (DXR)., Methods: The rats were divided into control, CAPE alone, doxorubicin (20 mg/kg, i.p.) and doxorubicin plus CAPE (10 micromol/kg/day, i.p.) groups. At the end of the 10th day, kidney tissues were removed for light microscopy and analysis. The levels of tissues protein carbonyl content (PC), malondialdehyde (MDA) and nitric oxide (NO) as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO) were determined. Plasma oxidants and antioxidants were also measured., Results: The activities of CAT and GSH-Px were decreased as well as myeloperoxidase, NO, MDA and PC were increased in renal tissue of doxorubicin group compared with the other groups. Plasma GSH-Px activity was higher in doxorubicin plus CAPE group than the others and plasma MDA level was higher in doxorubicin group than the other groups. There were glomerular vacuolization, tubular desquamation, loss of brush border, and adhesion to Bowman's in the light microscopy in the kidneys of doxorubicin group. The tubules and brush border were almost normal and some of the glomerulus was filled with fine vacuoles in CAPE treated rats., Conclusion: Doxorubicin caused renal injury and CAPE treatment prevented lipid peroxidation and protein oxidation in renal tissue and partially preserved glomerulus and tubules.

Because oxidative damage has been known to be involved in inflammatory and autoimmune-mediated tissue destruction, modulation of oxygen free radical production represents a new approach to the treatment of inflammatory and autoimmune diseases. Central nervous system tissue is particularly vulnerable to oxidative damage, suggesting that oxidation plays an important role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, has been determined to have antioxidant, anti-inflammatory, antiviral, and anticancer activities. We have previously reported that CAPE inhibits ischemia-reperfusion injury and oxidative stress in rabbit spinal cord tissue. The present study, therefore, examined effects of CAPE on oxidative tissue damage in EAE in rats. Treatment with CAPE significantly inhibited reactive oxygen species (ROS) production induced by EAE, and ameliorated clinical symptoms in rats. These results suggest that CAPE may exert its anti-inflammatory effect by inhibiting ROS production at the transcriptional level through the suppression of nuclear factor kappaB activation, and by directly inhibiting the catalytic activity of inducible nitric oxide synthase.

Caffeic acid phenethyl ester (CAPE), an active component of propolis, exhibits antioxidant properties. This experimental study was designed to determine the effect of CAPE on ototoxicity induced with cisplatin. Twenty-four adult Wistar albino rats were divided into four groups: cisplatin (n=6), saline (n=6), CAPE (n=6), and cisplatin plus CAPE (n=6). Rats were tested before and 5 days after cisplatin treatment with or without chemo protection. The Distortion Product Otoacoustic Emissions (DPOAEs) were elicited from the control and experimental animals utilizing the standard commercial Otoacoustic Emission (OAEs) apparatus. The animals in all groups were sacrificed under general anesthesia on the fifth day following last OAE measurements. For biochemical investigations, the blood samples were drawn from inferior vena cava. On day 0, the initial baseline DPOAEs measurement results presented similar values while comparing the groups in drug free phase (p>0.05). On day 5, intrasubject measurement parameters of DPgrams and I/O functions of cisplatin group were significantly deteriorated (p<0.05). The second measurements of the other groups revealed no significant differences between their DPgrams and I/O functions in all frequencies (p>0.05). Among the biochemical parameters, plasma xanthine oxidase (XO) activity was found to be more elevated in the cisplatin group than the saline group (p<0.05). CAPE led to more decreased XO activity than cisplatin (p<0.05). The results of this study show that prophylactic administration of CAPE for cisplatin ototoxicity ameliorated hearing deterioration in rats.

Background: Pulmonary fibrosis (PF) induced by anticancerogenic bleomycin (BLM) is one of the more common side effects encountered during cancer treatment. It has been suggested in the last decades that the main responsible agent in PF is reactive oxygen species which were generated also in normal physiological conditions in the human body. In this experimental study, we investigated the preventive or attenuating effects of caffeic acid phenethyl ester (CAPE) that has been demonstrated to have anti-inflammatory, cytocytatic, anticancerogenic, antiprolipherative and antioxidant effects on BLM-induced PF., Methods: Thirty-six Sprague-Dawley rats were divided randomly into four groups as sham operation, BLM, BLM + vitamin E (vit E), and BLM + CAPE groups. BLM (7.5 mg/kg, single dose) was applied intratracheally, and CAPE and vit E intraperitoneally in the appropriate groups. At the end of the fibrosis processes, lung tissues were removed and the levels of tissues hydroxyproline (OH-proline), malondialdehyde (MDA) and NO as well as the activities of superoxide dismutase (SOD), catalase (CAT) and myeloperoxidase (MPO) were determined. Also, the weights of the rats were recorded at 7th and 14th days of the experiments., Results: BLM application to the rats resulted in a significant increase in the OH-proline level as compared to the controls. Administration of CAPE and vit E led to the remarkable reduction of total lung OH-proline levels compared to the rats treated with BLM alone (p < 0.0001). There were a decreases in antioxidant enzyme (SOD and CAT) activities while an increase in MPO activity in BLM group was found vs. the control group (p < 0.0001). CAPE had a regulator effect on these parameters: the increase in CAT and SOD activities and the decrease in MPO activity were seen after CAPE application. NO, MDA and OH-proline levels were increased in BLM group vs. the control group. CAPE was more effective in decreasing the tissue levels of NO, MDA and OH-proline than vit E. MPO activity, as a good marker of neutrophil sequestration to the tissues, in the BLM group was decreased by CAPE approximately to the control group., Conclusion: We suggest that CAPE is more effective on the prevention of BLM-induced fibrosis via antioxidant and free radical scavenger properties than vit E at the doses used in the present study. CAPE has some attenuating effects on BLM-induced PF affecting both oxidant and antioxidant systems as well as neutrophils sequestration.

We have investigated the effect of caffeic acid phenethyl ester (CAPE) on cisplatin-induced nephrotoxicity in rats. Administration of a single dose of cisplatin resulted in the elevation of blood urea nitrogen and creatinine in serum, as well as nitric oxide in kidney tissue of rats. Cisplatin also caused reduction of catalase (P < 0.0001), superoxide dismutase (P = 0.149) and glutathrone peroxidase (P < 0.0001) activities in kidney tissue. Although cisplatin caused elevation in malondialdehyde levels and myeloperoxidase activities in kidney tissue, they were not statistically significant. Caffeic acid phenethyl ester was found to be protective against cisplatin-induced antioxidant enzyme reductions. Treatment with free-radical scavenger CAPE attenuated the increase in plasma blood urea nitrogen and kidney nitric oxide levels, and showed histopathological protection against cisplatin-induced acute renal failure. Extensive epithelial cell vacuolization, swelling, desquamation and necrosis were observed in the kidney of the cisplatin-treated rat. There were also larger tubular lumens in cisplatin-treated rats than those of the control and the CAPE groups. Caffeic acid phenethyl ester caused a marked reduction in the extent of tubular damage. It is concluded that administration of cisplatin imposes an oxidative stress to renal tissue and CAPE confers protection against the oxidative damage associated with cisplatin. This mechanism may be attributed to its free-oxygen-radical scavenging activity., (Copyright 2004 John Wiley & Sons, Ltd.)