Caffeic Acid Phenethyl Ester Pretreatment Research Articles

Caffeic Acid Phenethyl Ester Suppresses Oxidative Stress and Regulates M1/M2 Microglia Polarization via Sirt6/Nrf2 Pathway to Mitigate Cognitive Impairment in Aged Mice following Anesthesia and Surgery

Postoperative cognitive dysfunction (POCD) is a severe neurological complication after anesthesia and surgery. However, there is still a lack of effective clinical pharmacotherapy due to its unclear pathogenesis. Caffeic acid phenethyl ester (CAPE), which is obtained from honeybee propolis and medicinal plants, shows powerful antioxidant, anti-inflammatory, and immunomodulating properties. In this study, we aimed to evaluate whether CAPE mitigated cognitive impairment following anesthesia and surgery and its potential underlying mechanisms in aged mice. Here, isoflurane anesthesia and tibial fracture surgery were used as the POCD model, and H2O2-induced BV2 cells were established as the microglial oxidative stress model. We revealed that CAPE pretreatment suppressed oxidative stress and promoted the switch of microglia from the M1 to the M2 type in the hippocampus, thereby ameliorating cognitive impairment caused by anesthesia and surgery. Further investigation indicated that CAPE pretreatment upregulated hippocampal Sirt6/Nrf2 expression after anesthesia and surgery. Moreover, mechanistic studies in BV2 cells demonstrated that the potent effects of CAPE pretreatment on reducing ROS generation and promoting protective polarization were attenuated by a specific Sirt6 inhibitor, OSS_128167. In summary, our findings opened a promising avenue for POCD prevention through CAPE pretreatment that enhanced the Sirt6/Nrf2 pathway to suppress oxidative stress as well as favor microglia protective polarization.

Caffeic Acid Phenethyl Ester Protects against Experimental Autoimmune Encephalomyelitis by Regulating T Cell Activities.

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by progressive demyelination and disabling outcomes. CD4+ T cells are the most critical driving factor of relapsing MS, but little improvement has been noted upon deletion of the whole T cell population. Caffeic acid phenethyl ester (CAPE), one of the main active compounds of propolis, exhibits potent antitumour, anti-inflammatory, and antioxidant properties by suppressing nuclear factor-κB (NF-κB) transactivation. To investigate the therapeutic potential of CAPE in MS, we studied the effects of CAPE on cytokine levels, T cells, and NF-κB activities and in an experimental MS animal model. The results showed that cerebrospinal fluid (CSF) from patients with relapsing MS is characterized by increased levels of proinflammatory cytokines/chemokines that preferentially skew towards T helper 1 (Th1) cytokines. In vitro studies demonstrated that CAPE not only inhibited T cell proliferation and activation but also effectively modulated T cell subsets. Under both Th0- and Th1-polarizing conditions, the proportion of CD4+IFN-γ+ cells was downregulated, while CD4+Foxp3+ cells were increased. Moreover, nuclear translocation of NF-κB p65 was inhibited by CAPE. In a murine experimental autoimmune encephalomyelitis model, prophylactic treatment with CAPE significantly decreased the disease incidence and severity. Compared to the vehicle group, mice pretreated with CAPE showed diminished inflammatory cell infiltration, microglia/macrophage activation, and demyelination injury. Additionally, CAPE pretreatment reduced the level of Th1 cells in both spleen and the CNS and increased regulatory T cells (Tregs) in the CNS. In conclusion, our results highlight the potential merit of CAPE in suppressing T cell activity mainly through targeting the pathogenic Th1 lineage, which may be beneficial for MS treatment.

Caffeic acid phenethyl ester, a propolis polyphenolic, attenuates potentially cadmium-induced testicular dysfunction in mice

Cadmium (Cd) as environmental pollutant can induce severe damage, particularly to the testis. This study investigated the effects of Caffeic acid phenethyl ester (CAPE) on testicular dysfunction induced by Cd. Adult mice were intraperitoneally injected with cadmium chloride (CdCl2) with different doses of CAPE pretreatment. After CdCl2 injection, body/testis weight ratio decreased, Cd levels accumulated and zinc levels decreased in testis. Furthermore, Cd intoxication caused a significant increase of oxidative stress levels, antioxidant enzymes activities, and glutathione levels. Interestingly, significant improvements were observed after the administration of CAPE. Our results demonstrated the protective effect of CAPE, linking Cd testicular dysfunction to oxidative stress.

Caffeic acid phenethyl ester reduces the secretion of vascular endothelial growth factor through the inhibition of the ROS, PI3K and HIF-1α signaling pathways in human retinal pigment epithelial cells under hypoxic conditions.

Choroidal neovascularization (CNV) can lead to progressive and severe visual loss. Vascular endothelial growth factor (VEGF) promotes the development of CNV. Caffeic acid phenethyl ester (CAPE), a biologically active component of the honeybee (Apis mellifera) propolis, has been demonstrated to have several interesting biological regulatory properties. The objective of this study was to determine whether treatment with CAPE results in the inhibition of the production of vascular endothelial growth factor (VEGF) in retinal pigment epithelial cells (RPE cells) under hypoxic conditions and to explore the possible underlying mechanisms. An in vitro experimental model of hypoxia was used to mimic an ischemic microenvironment for the RPE cells. Human RPE cells (ARPE-19) were exposed to hypoxia with or without CAPE pre-treatment. ARPE-19 cells were used to investigate the pathway involved in the regulation of VEGF production under hypoxic conditions, based on western blot analysis, enzyme-linked immunosorbent assay (ELISA) and electrophoretic mobility shift assay (EMSA). The amount of VEGF released from the hypoxia-exposed cells was significantly higher than that of the normoxic controls. Pre-treatment with CAPE suppressed the hypoxia-induced production of VEGF in the ARPE-19 cells, and this effect was inhibited through the attenuation of reactive oxygen species (ROS) production, and the inhibition of phosphoinositide 3-kinase (PI3K)/AKT and hypoxia-inducible factor-1α (HIF-1α) expression. These in vitro findings suggest that CAPE may prove to be a novel anti-angiogenic agent for the treatment of diseases associated with CNV.

Value of Caffeic Acid Phenethyl Ester Pretreatment in Experimental Sepsis Model in Rats

Background and Aim. The aim of this study was to determine the actions of caffeic acid phenethyl ester (CAPE) on the changes of endothelin-1 (ET-1) level, tumor necrosis factor- (TNF-) alpha, and oxidative stress parameters such as superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels in experimental sepsis model in rats. Materials and Methods. Twenty-four rats were randomly divided into three experimental groups: sham (group 1), sepsis (group 2), and sepsis + CAPE (group 3), n = 8 each. CAPE was administered (10 µmol/kg) intraperitoneally to group 3 before sepsis induction. Serum ET-1, serum TNF-alpha, tissue SOD activity, and tissue MDA levels were measured in all groups. Results. Pretreatment with CAPE decreased ET-1, TNF-alpha, and MDA levels in sepsis induced rats. Additionally SOD activities were higher in rats pretreated with CAPE after sepsis induction. Conclusion. Our results demonstrate that CAPE may have a beneficial effect on ET and TNF-alpha levels and oxidative stress parameters induced by sepsis in experimental rat models. Therefore treatment with CAPE can be used to avoid devastating effects of sepsis.

Effect of caffeic acid phenethyl ester (CAPE) on H2O2 induced oxidative and inflammatory responses in human middle ear epithelial cells

ObjectiveAcute otitis media (OM) is a common pediatric disease. Recent research into the pathogenesis of OM has focused on oxidative damage, induced by oxygen free radicals, to the middle ear mucosa along with inflammation. Caffeic acid phenethyl ester (CAPE) is a biologically active ingredient of propolis honey bees, with antioxidative and anti-inflammatory activities. The effect of CAPE on hydrogen peroxide (H2O2)-induced inflammatory and oxidative reactions in the middle ear is still not known. The aim of this study was to evaluate the anti-inflammatory and antioxidative effects of CAPE on cultured human middle ear epithelial cells (HMEECs). MethodsThe inflammatory injury of H2O2 and the anti-inflammatory effect of CAPE were determined by measuring levels of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α and COX-2) with real-time reverse transcription polymerase chain reaction and Western blot analysis. Oxidative stress induced by H2O2 and antioxidative effects of CAPE were evaluated directly by reactive oxygen species (ROS) production using flow cytometric analysis of 5-(and-6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA), and indirectly by the expression of superoxide dismutase (SOD) using Western blot analysis. The effect of CAPE was compared with N-acetyl cysteine (NAC) which has well-known antioxidative and anti-inflammatory effects. ResultsCAPE significantly inhibited H2O2-induced upregulation of TNF-α and COX-2 expression in a dose and time dependent manner. ROS accumulation induced by H2O2 stimulation was decreased by CAPE pretreatment. Induced SOD expression after H2O2 stimulation was diminished by CAPE pretreatment. The anti-inflammatory and antioxidative effects of CAPE were similar to those of NAC. ConclusionsThese findings suggest that inflammation induced by H2O2 can be inhibited by CAPE via inhibition of the expression of pro-inflammatory cytokines such as TNF-α and COX-2. Furthermore, CAPE has antioxidative effects, which decreases the need for endogenous SOD expression.

Caffeic acid phenethyl ester suppresses eotaxin secretion and nuclear p-STAT6 in human lung fibroblast cells

Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been proven to have anti-inflammatory and antiallergic properties. We have investigated the activity of CAPE in regulating cytokine-induced eotaxin production and its related signal protein, signal transducer and activator of transcription 6 (STAT6), in human lung fibroblast. The CCD-11Lu human lung fibroblast cell line was used as an in vitro model. Cells were pretreated with CAPE followed by stimulation with interleukin-4 and tumor necrosis factor alpha. The levels of eotaxin in cultured supernatants were measured by enzyme-linked immunosorbent assay. The amounts of STAT6 and phosphorylated STAT6 in cellular nuclear protein extracts were determined by Western blot analysis. STAT6 DNA binding activities were detected by electrophoretic mobility shift assay. Pretreated CCD-11Lu cells with noncytotoxic doses (0.1-10 μM) of CAPE inhibited the production of eotaxin under stimulation of interleukin-4 (10 ng/mL) and tumor necrosis factor alpha (10 ng/mL). CAPE pretreatment also decreased the amount of phosphorylated STAT6 and the STAT6 DNA binding complexes in nuclear extracts. CAPE inhibited the production of eotaxin protein in stimulated human lung fibroblast cells in a dose-dependent manner. This activity is, at least, through STAT6 inhibition. We suggest that CAPE is a promising agent in controlling eotaxin secretion and subsequent eosinophils influx and may therefore have a potential role to play in treating allergic airway disease.

Effects of caffeic acid phenethyl ester on endotoxin‐induced cardiac stress in rats: A possible mechanism of protection

Endotoxins (lipopolysaccharides; LPS) are known to cause multiple organ failure, including myocardial dysfunction. The present study aimed to investigate the mechanism of caffeic acid phenethyl ester (CAPE) protection against LPS-induced cardiac stress. Rats were allocated into three groups; group 1 served as a normal control group, group 2 (LPS) received a single intraperitoneal injection of LPS (10 mg/kg), group 3 (LPS + CAPE) was injected intraperitoneally with CAPE (10 mg/kg/day; solubilized in saline containing 20% tween 20) throughout a period of 10 days prior to LPS injection. Rats were maintained 4 h before sacrifice. Caffeic acid phenethyl ester pretreatment normalized LPS-enhanced activities of serum creatine kinase (CK) and lactate dehydrogenase (LDH) as well as glutathione peroxidase (GPx), and myeloperoxidase (MPO) in cardiac tissue. A significant reduction of the elevated levels of serum tumor necrosis factor-alpha (TNF-α) as well as serum and cardiac nitrite/nitrate (NOx) ) was achieved after CAPE pretreatment. CAPE also restored malondialdelyde (MDA), reduced glutathione (GSH), and cytosolic calcium (Ca2+ ) levels in the heart. A marked induction of cardiac heme oxygenase-1 (HO-1) protein level was detected in CAPE-pretreated group. Whereas, LPS-induced reduction of adenosine triphosphate (ATP) and phosphocreatine (PCr) levels was insignificantly changed. Conclusively, the early treatment with CAPE maintained antioxidant defences, reduced oxidative injury, cytokine damage, and inflammation but did not markedly improve energy status in cardiac tissue. The beneficial effect of CAPE might be mediated, at least in part, by the superinduction of HO-1.

Caffeic Acid Phenethyl Ester, an Antioxidant from Propolis, Protects Peripheral Blood Mononuclear Cells of Competitive Cyclists against Hyperthermal Stress

Hyperthermal stress and resulting free radical generation is known to impair endurance capacity and immune cell redistribution during prolonged exercise. Caffeic acid phenethyl ester (CAPE), a phenolic compound purified from propolis, has many biological and pharmacological activities including antioxidation. To examine whether CAPE has protective effect against hyperthermal stress in athletes, we isolated peripheral blood mononuclear cells (MNC) from competitive cyclists and assessed their response to hyperthermia with or without CAPE pretreatment. We found that pretreatment of cyclists' MNC with CAPE (0, 1, 2, 4 microg/mL) reversed or reduced hyperthermia-induced survival inhibition, necrosis, superoxide production, glutathione depletion, and intracellular superoxide burst in a dose-dependent manner. These results suggest that CAPE may enhance the hyperthermal tolerance in immune mononuclear cells of competitive cyclists.

Caffeic acid phenethyl ester preferentially enhanced radiosensitizing and increased oxidative stress in medulloblastoma cell line

Caffeic acid phenethyl ester (CAPE), an active component of propolis, was recently reported to have radiosensitizing effects on medulloblastoma (MB) cells. However, the mechanisms of radiosensitivity involved in medulloblastoma cells are still unclear. The specific aim of this study was to investigate the role of CAPE-induced oxidative stress to influence of radiosensitivity and anti-proliferative effects in medulloblastoma cells. Medulloblastoma (Daoy) cells were treated with CAPE in different concentrations and assessed for cell viability. The following were also evaluated: migratory ability, reduced glutathione (GSH) level, reactive oxygen species (ROS) level, nuclear factor-kappaB (NF-kappaB) activity, and apoptosis in CAPE alone, radiation alone, or radiation combined with CAPE in Daoy cells. The results indicated that CAPE inhibited the growth of Daoy cells. CAPE treatment in Daoy cells could effectively decrease glutathione reductase and significantly increase glutathione peroxidase. Radiation-activated NF-kappaB was reversed by CAPE pretreatment. Finally, the result of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay showed that CAPE treatment can enhance radiation-induced apoptosis in Daoy cells. Our study demonstrated the anti-proliferative and radiosensitizing effects of CAPE on MB cells, which may be achievable through depleting GSH, increased ROS activity, and inhibiting NF-kappaB activity.

Inhibitory effect of caffeic acid phenethyl ester (CAPE) on LPS-induced inflammation of human middle ear epithelial cells

Conclusions. The results suggest that the anti-inflammatory effect of caffeic acid phenethyl ester (CAPE) is due to its inhibition of tumor necrosis factor (TNF)-α expression and interleukin (IL)-8 production. The anti-inflammatory effect of CAPE is possibly through the inhibition of nuclear factor (NF)-κB via the suppression of inhibitor-κB-α (IκB-α) degradation. Objectives. CAPE is a biologically active component of propolis, a resinous material obtained from bee hives, which originates from conifer bark. The effect of CAPE on lipopolysaccharide (LPS)-induced inflammatory reactions is not known. The aim of this study was to evaluate the anti-inflammatory effect of CAPE on cultured human middle ear epithelial cells (HMEECs). Materials and methods. The effect of CAPE on LPS-induced TNF-α expression was evaluated in HMEECs by real-time reverse transcription polymerase chain reaction (RT-PCR). LPS-induced IL-8 production was determined by enzyme-linked immunosorbent assay (ELISA), and LPS-induced IκB-α degradation was followed by Western blot analysis. Results. CAPE significantly inhibited LPS-induced up-regulation of TNF-α in a dose-dependent manner. IL-8 production by LPS was significantly suppressed by the CAPE pretreatment. Furthermore, LPS-induced IκB-α degradation was suppressed by the CAPE pretreatment.

Differential regulation of c‐Jun N‐terminal kinase and NF‐κB pathway by caffeic acid phenethyl ester in astroglial and monocytic cells

Caffeic acid phenethyl ester (CAPE), an active component of propolis extracts, has been known for its specific inhibition of nuclear factor kappaB (NF-kappaB) and subsequent anti-inflammatory activity. In this study, we report that (i) CAPE exerts its anti-inflammatory action (inhibition of tumor necrosis factor-induced expression of intercellular adhesion molecule-1 and CC chemokine ligand-2) via NF-kappaB inhibition by two distinct molecular mechanisms in a cell-specific manner: CAPE inhibited downstream pathways of inhibitor kappaB (IkappaB) degradation in monocytic cells, while activation of upstream IkappaB kinase was suppressed by CAPE pre-treatment in astroglial cells; and (ii) CAPE paradoxically activates the c-Jun N-terminal kinase (JNK) pathway, which might be responsible for its pro-apoptotic action and divergent regulation of proinflammatory mediators such as CXC chemokine ligand-8.

Caffeic acid phenethyl ester decreases acute pneumonitis after irradiation in vitro and in vivo

BackgroundLung cancer is relatively resistant to radiation treatment and radiation pneumonitis is a major obstacle to increasing the radiation dose. We previously showed that Caffeic acid phenethyl ester (CAPE) induces apoptosis and increases radiosensitivity in lung cancer. To determine whether CAPE, an antioxidant and an inhibitor of NF-kappa B, could be a useful adjuvant agent for lung cancer treatment, we examine the effects of CAPE on irradiated normal lung tissue in this study.MethodsWe compared the effects of CAPE on cytotoxicity and intracellular oxidative stress in normal lung fibroblast and a lung cancer cell line. For in vivo analysis, whole thorax radiation (single dose 10 Gy and 20 Gy) was delivered to BALB/c male mice with or without CAPE pretreatment. NF- kappaB activation and the expression levels of acute inflammatory cytokines were evaluated in mice after irradiation.ResultsThe in vitro studies showed that CAPE cause no significant cytotoxicity in normal lung as compared to lung cancer cells. This is probably due to the differential effect on the expression of NF-kappa B between normal and malignant lung cells. The results from in vivo study showed that CAPE treatment decreased the expression of inflammatory cytokines including IL-1 alpha and beta, IL-6, TNF-alpha and TGF- beta, after irradiation. Moreover, histological and immunochemical data revealed that CAPE decreased radiation- induced interstitial pneumonitis and TGF-beta expression.ConclusionThis study suggests that CAPE decreases the cascade of inflammatory responses induced by thoracic irradiation without causing toxicity in normal lung tissue. This provides a rationale for combining CAPE and thoracic radiotherapy for lung cancer treatment in further clinical studies.

Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse

Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-kappaB activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses of CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or gamma-glutamyl transpeptidase activity. Radiation activated NF-kappaB was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity. CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-kappaB activity, without toxicity to bone marrow, liver, and kidney.

Gentamicin‐induced nephrotoxicity and protective effect of caffeic acid phenethyl ester in rats

The objective of this study was to investigate the beneficial effects of caffeic acid phenethyl ester (CAPE) on gentamicin (GM)-induced nephrotoxicity in Wistar rats. Twenty-one adult Wistar rats were divided into three groups as follows: control group, GM and GM + CAPE group. Control group rats were injected with 5% ethanol, GM group rats were treated with 100 mg/kg GM and GM + CAPE group were pretreated with 10 mumol/kg CAPE for 2 days, then exposed to GM at the same dose. Drug injections were applied for 12 days. Twenty-four hours after the last injection, rats were killed and kidneys were quickly removed. Tissue malondialdehyde (MDA) measurements and microscopic examination of kidneys were performed. In the GM group, significant increases in MDA levels were observed (P < 0.05). These changes were found to be normalized in the GM + CAPE group. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules were found to be prevented by CAPE pretreatment. In conclusion, CAPE exerted an improvement on GM-induced nephrotoxicity, possibly, at least in part through inhibition of the production of oxygen free radicals that cause lipid peroxidation.

The effects of the caffeic acid phenethyl ester (CAPE) on erythrocyte membrane damage after hind limb ischaemia-reperfusion.

Reactive oxygen species have been implicated in pathogenesis injury after ischaemia-reperfusion (I/R). Caffeic Acid Phenethyl Ester (CAPE), an active component of honeybee propolis extract, exhibits antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of CAPE on erythrocyte membrane damage after hind limb I/R. Rats were divided into two groups: I/R and I/R with CAPE pre-treatment. They were anaesthetized with intramuscular ketamine 100 mg kg(-1). A 4-h I/R period was performed on the right hind limb of all animals. In the CAPE-treated group, animals received CAPE 10 microm by intraperitoneal injection 1 h before the reperfusion. At the end of the reperfusion period, a midsternotomy was performed. A 5-ml blood sample was withdrawn from the ascending aorta for biochemical assays. Serum and erythrocyte membrane MDA levels were significantly lower in the CAPE-treated group when compared to the I/R group ( p = 0.001 and p<0.001, respectively). Erythrocyte membrane Na(+)-K(+) ATPases activity in the CAPE-treated group was significantly higher than the I/R group ( p<0.001). In conclusion, CAPE seems to be effective in protecting against oxidative stress. Therefore, we suggest that in order to decrease I/R injury, pre-administration of CAPE may be a promising agent for a variety of conditions associated with I/R.

Protective effects of caffeic acid phenethyl ester on doxorubicin-induced cardiotoxicity in rats.

The prevention of doxorubicin (DXR)-induced cardiotoxicity may be helpful to improve future DXR therapy. The aim of this study was to investigate the cardio-protective effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, on DXR-induced cardiotoxicity. Rats were divided into three groups and treated with saline, DXR and DXR + CAPE. Rats were treated with CAPE (10 micromol x kg(-1) day(-1) i.p.) or saline starting 2 days before a single dose of DXR (20 mg x kg(-1) i.p.). Ten days later, haemodynamic measurements were performed and the hearts were excised for biochemical analyses and microscopic examination. The heart rate and mean blood pressure were higher and the pulse pressure was lower in the DXR group than in the other two groups. The administration of DXR alone resulted in higher myeloperoxidase activity, lipid peroxidation and protein carbonyl content than in the other groups. The activities of superoxide dismutase and catalase were higher in DXR and DXR + CAPE groups than in the saline group. Rats in the DXR + CAPE group had increased catalase activity in comparison with the DXR group and high glutathione peroxidase activity in comparison with the other two groups. There was severe disruption of mitochondrial fi ne structure in the electron microscopy of the DXR group. In contrast, myocardial microscopy appeared nearly normal in the DXR + CAPE group (as de fi ned at the electron microscopic level). In light of these in vivo haemodynamic, enzymatic and morphological results, we conclude that CAPE pretreatment significantly attenuated DXR-induced cardiac injury, possibly with its antioxidant effects.