Gellan-Based Hydrogel as a Drug Delivery System for Caffeic Acid Phenethyl Ester in the Treatment of Oral Candida albicans Infections.

Candida albicans can cause various types of oral infections, mainly associated with denture stomatitis. Conventional therapy has been linked to high recurrence, toxicity, and fungal resistance, necessitating the search for new drugs and delivery systems. In this study, caffeic acid phenethyl ester (CAPE) and gellan gum (GG) were studied as an antifungal agent and carrier system, respectively. First, we observed that different GG formulations (0.6 to 1.0% wt/vol) were able to incorporate and release CAPE, reaching a controlled and prolonged release over 180 min at 1.0% of GG. CAPE-GG formulations exhibited antifungal activity at CAPE concentrations ranging from 128 to >512 µg/mL. Furthermore, CAPE-GG formulations significantly decreased the fungal viability of C. albicans biofilms at short times (12 h), mainly at 1.0% of GG (p < 0.001). C. albicans protease activity was also reduced after 12 h of treatment with CAPE-GG formulations (p < 0.001). Importantly, CAPE was not cytotoxic to human keratinocytes, and CAPE-GG formulations at 1.0% decreased the fungal burden (p = 0.0087) and suppressed inflammation in a rat model of denture stomatitis. Altogether, these results indicate that GG is a promising delivery system for CAPE, showing effective activity against C. albicans and potential to be used in the treatment of denture stomatitis.

Caffeic Acid Phenethyl Ester (CAPE): Biosynthesis, Derivatives and Formulations with Neuroprotective Activities.

Neurodegenerative disorders are characterized by a progressive process of degeneration and neuronal death, where oxidative stress and neuroinflammation are key factors that contribute to the progression of these diseases. Therefore, two major pathways involved in these pathologies have been proposed as relevant therapeutic targets: The nuclear transcription factor erythroid 2 (Nrf2), which responds to oxidative stress with cytoprotecting activity; and the nuclear factor NF-κB pathway, which is highly related to the neuroinflammatory process by promoting cytokine expression. Caffeic acid phenethyl ester (CAPE) is a phenylpropanoid naturally found in propolis that shows important biological activities, including neuroprotective activity by modulating the Nrf2 and NF-κB pathways, promoting antioxidant enzyme expression and inhibition of proinflammatory cytokine expression. Its simple chemical structure has inspired the synthesis of many derivatives, with aliphatic and/or aromatic moieties, some of which have improved the biological properties. Moreover, new drug delivery systems increase the bioavailability of these compounds in vivo, allowing its transcytosis through the blood-brain barrier, thus protecting brain cells from the increased inflammatory status associated to neurodegenerative and psychiatric disorders. This review summarizes the biosynthesis and chemical synthesis of CAPE derivatives, their miscellaneous activities, and relevant studies (from 2010 to 2023), addressing their neuroprotective activity in vitro and in vivo.

Role of inflammation and oxidative stress in tissue damage associated with cystic fibrosis: CAPE as a future therapeutic strategy.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, responsible for the synthesis of the CFTR protein, a chloride channel. The gene has approximately 2000 known mutations and all of them affect in some degree the protein function, which makes the pathophysiological manifestations to be multisystemic, mainly affecting the respiratory, gastrointestinal, endocrine, and reproductive tracts. Currently, the treatment of the disease is restricted to controlling symptoms and, more recently, a group of drugs that act directly on the defective protein, known as CFTR modulators, was developed. However, their high cost and difficult access mean that their use is still very restricted. It is important to search for safe and low-cost alternative therapies for CF and, in this context, natural compounds and, mainly, caffeic acid phenethyl ester (CAPE) appear as promising strategies to assist in the treatment of the disease. CAPE is a compound derived from propolis extracts that has antioxidant and anti-inflammatory activities, covering important aspects of the pathophysiology of CF, which points to the possible benefit of its use in the disease treatment. To date, no studies have effectively tested CAPE for CF and, therefore, we intend with this review to elucidate the role of inflammation and oxidative stress for tissue damage seen in CF, associating them with CAPE actions and its pharmacologically active derivatives. In this way, we offer a theoretical basis for conducting preclinical and clinical studies relating the use of this molecule to CF.

Novas estratégias terapêuticas para o controle de biofilmes orais: terapia fotodinâmica e sistema carreador de antimicrobianos / New therapeutic strategics for the control of oral biofilms: photodynamic therapy and drug delivery system

Os biofilmes orais possuem grande relevância clínica por estarem associados com o desenvolvimento de cárie dentária e candidose bucal, que são doenças infecciosas frequentemente encontradas na população. O presente trabalho foi dividido em dois estudos: Estudo 1 que teve como objetivo analisar os efeitos da terapia fotodinâmica antimicrobiana (TFDa), mediada por Fotoenticine (FTC) e Azul de Metileno (AM), sobre biofilmes microcosmos de cárie dentária; e Estudo 2 cujo objetivo foi avaliar o gellan gum como biomaterial para carreador do antifúngico Ester fenetil do ácido caféico (CAPE) contra Candida albicans. No estudo 1, amostras de dentina cariada foram coletadas de diferentes pacientes para formar biofilmes microcosmos in vitro. Os biofilmes foram tratados com FTC ou AM associado à irradiação LED a 660 nm (28,5 J/cm²). Os dados foram analisados pela contagem de Unidades Formadoras de Colônias (UFC/mL). Além disso, a biomassa, estrutura do biofilme e produção de ácidos pelos microrganismos foram determinadas por análises microscópicas ou espectrofotométricas. Os biofilmes de diferentes pacientes apresentaram variações na composição microbiana, sendo formados por estreptococos, lactobacilos e leveduras. No geral, a TFDa diminuiu 3,7 Log10 do total de microrganismos, 2,8 Log10 de estreptococos, 3,2 Log10 de lactobacilos e 3,2 Log10 de leveduras, e atingiu a erradicação de estreptococos do grupo mutans. A TFDa também foi capaz de reduzir a biomassa, desagregar os biofilmes e diminuir a concentração de ácidos em 1,1 a 1,9 mmol de lactato/L. Em relação ao estudo 2, inicialmente, foram preparadas formulações do CAPE em diferentes concentrações de gellan gum (0,6 a 1%). As formulações foram avaliadas em relação ao sistema de liberação e ação antifúngica contra C. albicans. Verificou-se que concentrações mais altas de gellan (0,9 e 1%) levaram a uma liberação mais prolongada do CAPE em relação as concentrações mais baixas. Os valores de concentração inibitória mínima do CAPE sobre C. albicans foram aumentados quando esse composto foi incorporado no gellan. As formulações de CAPE em gellan apresentaram atividade antifúngica tanto em culturas planctônicas como em biofilmes de C. albicans, sendo esses efeitos dependentes do tempo de tratamento. O CAPE e suas formulações em gellan também levaram a uma diminuição da atividade proteolítica de C. albicans. Concluiu-se que a TFDa mediada por Fotoenticine e o sistema carreador de gellan gum podem ser estratégias terapêuticas promissoras para o controle dos biofilmes na cavidade bucal, podendo ser usadas respectivamente no tratamento da cárie e candidose. (AU)

Dental caries and oral candidiasis are infectious diseases frequently found in the population. The present work is divided into two studies, study 1 time as objective: To analyze the effects of antimicrobial photodynamic therapy (aPDT), mediated by Fotoenticine (FTC) and Methylene Blue (MB), on dental caries microcosm biofilms. In study 2, the objective was to evaluate gellan gum as a biomaterial to carry the antifungal caffeic acid phenethyl ester (CAPE) on Candida albicans. To conduct study 1, carious dentin samples were collected from different patients to form in vitro microcosm biofilms. The biofilms were treated with FTC or MB associated with 660 nm red LED irradiation, with energy dose of 28.5 J/cm² and power dose of 40 mW/cm². The data were analyzed by the count of Colony Forming Units (CFU/mL). In addition, the biomass, biofilm structure and acid production of the microorganisms were determined by microscopic or spectrophotometric analysis. The biofilms from different patients showed variations in microbial composition, being formed by streptococci, lactobacilli, and yeasts. Overall, aPDT decreased 3.7 Log10 of total microorganisms, 2.8 Log10 of streptococci, 3.2 Log10 of lactobacilli and 3.2 Log10 of yeasts, and achieved eradication of mutans group streptococci. PDTa was also able to reduce biomass, disaggregate biofilms, and decrease acid concentration by 1.1 to 1.9 mmol lactate/L. For study 2 of this, first the standards of CAPE were determined, such as minimum inhibitory concentration, and absorption peak, then CAPE was incorporated into gellan gum, and then the standard curve test and analysis of CAPE release was performed, finally the formulations were tested on planktonic culture and biofilm of different strains of C. albicans, it was also analyzed the action of this drug on the production of Sap. The MIC found varied from 32 to 64 µg/mL, the release tests showed a gradual release in the higher formulations, finally in the CFU/mL count both in planktonic culture and biofilm the formulations were able to inhibit the fungus. With this it is concluded that both aPDT for oral microcosm and gellan gum as caregiver of CAPE for Candida albicans inhibition are promising. (AU)

The Anti-Biofilm Efficacy of Caffeic Acid Phenethyl Ester (CAPE) In Vitro and a Murine Model of Oral Candidiasis.

Candida albicans is the main fungal species associated with the development of oral candidiasis. Currently, therapeutic options for these infections are limited by the adverse effects of antifungal drugs and by the emergence of drug resistant strains. Thus, the development of new antifungal agents is needed for the prevention and treatment of oral Candida infections. Caffeic acid phenethyl ester (CAPE) is a natural compound from propolis polyphenolic groups that exhibits many pharmacological properties. In this study, we investigated whether CAPE can have antifungal and immunomodulatory effects on oral candidiasis. Preliminary tests to assess the antifungal activity of CAPE were performed using the Minimum Inhibitory Concentration (MIC) assay that demonstrated inhibition in a range from 16 to 32 µg/mL, confirming its antifungal activity on several C. albicans strains isolated from the oral cavity. Subsequently, we analyzed Candida spp biofilms formed in vitro, in which CAPE treatment at 5 x MIC caused a reduction of 68.5% in the total biomass and ~2.60 Log in the viable cell count (CFU/mL) in relation to the untreated biofilm (p<0.0001). Next, RNA was extracted from untreated and CAPE-treated biofilms and analyzed by real-time qPCR. A series of genes analyzed (ALS1, ECE1, EPA1, HWP1, YWP1, BCR1, BGR1, CPH1, EFG1, NDT80, ROB1, TEC1, UME6, SAP2, SAP5, PBL2, and LIP9) were downregulated by CAPE compared to the untreated control group (p<0.0001). In in vivo studies using Galleria mellonella, the treatment with CAPE prolonged survival of larvae infected by C. albicans by 44.5% (p < 0.05) and accompanied by a 2.07-fold increase in the number of hemocytes. Flow cytometry revealed the most prominent increases were in types P2 and P3 hemocytes, granular cells, which phagocytize pathogens. In addition, CAPE treatment decreased the fungal load in the hemolymph and stimulated the expression of antifungal peptide genes such as galiomicin and gallerimycin. The antifungal and immunomodulatory activities observed in G. mellonella were extended to a murine model of oral candidiasis, in which CAPE decreased the levels of C. albicans colonization (~2 log CFU/mL) in relation to the untreated control group. In addition, CAPE treatment significantly reduced pseudomembranous lesions, invasion of hyphae on epithelium surfaces, tissue damage and inflammatory infiltrate (p < 0.05). CAPE was also able to increase the expression of ß-defensin 3 compared to the infected and untreated group by 3.91-fold (p < 0.0001). Taken together, these results show that CAPE has both antifungal and immunomodulatory effects, making it a promising natural antifungal agent for the treatment and prevention of candidiasis and shows impact to oral candidiasis.

Low concentrations of caffeic acid phenethyl ester stimulate osteogenesis in vitro.

OBJECTIVE: The aim of this study was to evaluate the effects of caffeic acid phenethyl ester (CAPE) on osteoblast-like cell cultures (SAOS-2). METHODS: SAOS-2 were exposed to CAPE at 1 nM, 10 nM, 100 nM, 1 µM, and 10 µM. Non-exposed cultures were used as control. The following parameters were assayed: 1) cell viability at 1, 3, and 7 days; 2) alkaline phosphatase (ALP) activity at 5 and 10 days; 3) matrix mineralization at 14 days; and 4) Runt-related transcription factor 2 (RUNX2), ALP, osteopontin (SPP1), and osteocalcin (BGLAP) gene expression at 5 and 10 days. The data were analyzed by ANOVA two-way or Kruskal-Wallis (α = 5%). RESULTS: At day 1, cell viability was similar among all groups (p > 0.05). At days 3 and 7, cultures exposed to CAPE at 10 µM exhibited a significant reduction in cell viability compared with the others groups (p < 0.05). At day 5, ALP activity was similar among all experimental groups; at day 10, however, the stain intensity was higher in cultures exposed to CAPE at 100 nM and 10 nM in comparison with the other groups (p < 0.05). At days 5 and 10, RUNX2, ALP, SPP1, and BGLAP gene expression was greater in cultures exposed to CAPE in comparison with the control (p < 0.05). At day 14, matrix mineralization was similar in cultures exposed to CAPE at 1 nM and 10 nM (p > 0.05), but superior to those ones observed in the other experimental groups (p < 0.05). CONCLUSION: CAPE at low concentrations can positively module the osteogenesis in vitro.

Experimental Evidence for Therapeutic Potentials of Propolis.

Propolis is produced by honeybees from materials collected from plants they visit. It is a resinous material having mixtures of wax and bee enzymes. Propolis is also known as bee glue and used by bees as a building material in their hives, for blocking holes and cracks, repairing the combs and strengthening their thin borders. It has been extensively used since ancient times for different purposes in traditional human healthcare practices. The quality and composition of propolis depend on its geographic location, climatic zone and local flora. The New Zealand and Brazilian green propolis are the two main kinds that have been extensively studied in recent years. Their bioactive components have been found to possess a variety of therapeutic potentials. It was found that Brazilian green propolis improves the cognitive functions of mild cognitive impairments in patients living at high altitude and protects them from neurodegenerative damage through its antioxidant properties. It possesses artepillin C (ARC) as the key component, also known to possess anticancer potential. The New Zealand propolis contains caffeic acid phenethyl ester (CAPE) as the main bioactive with multiple therapeutic potentials. Our lab performed in vitro and in vivo assays on the extracts prepared from New Zealand and Brazilian propolis and their active ingredients. We provided experimental evidence that these extracts possess anticancer, antistress and hypoxia-modulating activities. Furthermore, their conjugation with γCD proved to be more effective. In the present review, we portray the experimental evidence showing that propolis has the potential to be a candidate drug for different ailments and improve the quality of life.

The ameliorative effects of caffeic acid phenethyl ester in cisplatin-induced nephrotoxicity: assessment of the oxidative stress an inflammation / Los efectos de mejora del éster fenetílico del ácido cafeico en la nefrotoxicidad inducida por cisplatino: evaluación del estrés oxidativo y la inflamación

SUMMARY: The aim of this study is to determine the potential therapeutic effects of CAPE in CP-induced nephrotoxicity in rats. Cisplatin (CP) is an antineoplastic chemotherapeutic used for treatment of many cancer types but its applications may induce nephrotoxicity. Caffeic acid phenethyl ester (CAPE) is an active component of propolis and it has several important physiological activities. Rats were divided into four groups: Control, CAPE (10 µmol/kg/i.p), CP (7 mg/kg/i.p), and CP+CAPE (7 mg/kg/i.p, CP and 10 µmol/kg/i.p, CAPE). After administrations, animals were sacrificed, and kidney tissues were extracted. Histopathological changes were evaluated and TNF-α and IL-6 immunostaining were performed. Moreover, tissue SOD, CAT and MDA levels were measured by ELISA assay to assessment of oxidative stress and lipid peroxidation. CP group showed histopathological deterioration compared to the Control group and CAPE treatment attenuated this damage. When compared with Control and CAPE group, an increase in TNF-α and IL-6 immunoreactivities and tissue MDA levels were observed in the CP group while a decrease in tissue SOD and CAT levels were detected. Furthermore, an improvement was observed in the CP+CAPE compared to the CP group. We suggest that CAPE can be used as a therapeutic agent to attenuate the toxic effects of cisplatin, thanks to its antioxidant and anti-inflammatory properties.

RESUMEN: El objetivo de este estudio fue determinar los posibles efectos terapéuticos de éster fenetílico del ácido cafeico (EFAC) en la nefrotoxicidad inducida por cisplatino (CP) en ratas. El CP es un quimioterapéutico antineoplásico utilizado para el tratamiento de muchos tipos de cáncer, sin embargo sus aplicaciones pueden inducir nefrotoxicidad. El EFAC es un componente activo del propóleo y tiene varias actividades fisiológicas importantes. Para el estudio las ratas se dividieron en cuatro grupos: Control, EFAC (10 µmol / kg / ip), CP (7 mg / kg / ip) y CP + EFAC (7 mg / kg / ip, CP y 10 µmol / kg / ip, EFAC). Después de las administraciones, se sacrificaron los animales y se extrajeron los tejidos renales. Se evaluaron los cambios histopatológicos y se realizó inmunotinción de TNF-α e IL-6. Además, los niveles tisulares de SOD, CAT y MDA se midieron mediante un ensayo ELISA para evaluar el estrés oxidativo y la peroxidación lipídica. El grupo CP mostró deterioro histopatológico en comparación con el grupo Control y el tratamiento con EFAC atenuó este daño. En comparación con el grupo de control y EFAC, se observó un aumento en las inmunorreactividades de TNF-α e IL-6 y los niveles de MDA en el tejido en el grupo de CP, mientras que se detectó una disminución en los niveles de SOD y CAT en los tejidos. Además, se observó una mejora en el CP + EFAC en comparación con el grupo CP. Sugerimos que EFAC puede utilizarse como agente terapéutico para atenuar los efectos tóxicos del cisplatino, gracias a sus propiedades antioxidantes y antiinflamatorias.

Protective Effects of Caffeic Acid Phenethyl Ester on Isoniazid and Rifampicin-induced Hepatic and Pancreatic Injury

ABSTRACT Objective: To investigate the protective effects of caffeic acid phenethyl ester (CAPE) against isoniazid (INH)- and rifampicin (RFP)-induced hepatic and pancreatic damage. Methods: Eighty adult rats were randomly divided into eight groups: control, INH, RFP, INH+RFP, INH+CAPE, RFP+CAPE, INH+RFP+CAPE, and CAPE. Both INH and RFP were orally administered for 30 days at a dose of 50 mg/kg/day. Caffeic acid phenethyl ester was intraperitoneally injected for 30 days (10 μmol/kg). Blood samples, hepatic and pancreatic tissues were obtained on day 30. Results: Total oxidant status levels were significantly higher in INH and/or RFP-treated groups than those of control and CAPE groups, while total antioxidant status and paraoxonase levels were significantly reduced in INH-RFP groups compared with the group receiving CAPE. Histopathological deterioration was observed in RFP and INH groups in pancreatic and hepatic tissue. However, significant amelioration was observed in CAPE-treated groups. Conclusion: Our findings suggest that CAPE may be a promising agent to prevent the side effects of INH and RFP treatment on hepatic and pancreatic tissues.

Propolis and Caffeic Acid Phenethyl Ester Attenuates Nitrosative Stress in Lens Tissue in Radiation-induced Cataracts in Rats

ABSTRACT Objective: Eye morbidity is widely observed in patients receiving total body irradiation prior to bone marrow transplantation or radiotherapy for ocular or head and neck cancers. Cataract blindness is the major cause of preventable blindness worldwide, especially in the developing countries. The aim of this study was to investigate whether propolis and caffeic acid phenethyl ester (CAPE) prevent radiation-induced cataractogenesis. Methods: Fifty-four Sprague-Dawley rats were randomly divided into six groups. Group 1 (irradiation (IR) + propolis) received total cranium irradiation and propolis was given orally through an orogastric tube daily. Group 2 (IR+CAPE) received total cranium irradiation plus CAPE intraperitoneally every day. Group 3 (IR) received 5 Gy of gamma irradiation as a single dose to total cranium plus 1 ml saline daily. Group 4 received daily plain saline. Group 5 received daily plain dimethyl sulfoxide. Group 6 (normal control group) did not receive anything. Results: At the end of the 10-day time period, cataracts developed in 80% of the rats in group 3 (IR group). After irradiation, cataract rate drop to 30% and 40% in groups treated with propolis and CAPE, respectively. Nitric oxide synthase activity, nitric oxide (NO•) and peroxynitrite (ONOO-) levels were significantly higher in group 3 compared to all other groups. Conclusion: The results suggest that propolis and CAPE have free radical scavenging activities in the irradiation-induced cataractogenesis, and reduced nitrosative stress markers. Prop-olis was found to be more effective in anticataractogenic effect than CAPE.

Propolis polyphenolic compounds affect the viability and structure of Helicobacter pylori in vitro

ABSTRACT To evaluate the anti-Helicobacter pylori activity of the major polyphenol compounds of propolis and their cellular damage, both as single molecule or in combination. Honey bees propolis were fractionated by using CPC and preparative HPLC. Four major polyphenols (chrysin, pinocembrin, galangin and caffeic acid phenethyl ester) were identified by thin layer chromatography-mass spectroscopy and liquid chromatography-mass spectroscopy. These compounds inhibited both ATCC and clinical H. pylori strains, with caffeic acid phenethyl ester being the most active. The four compounds presented minimum inhibitory concentration in the range 256-1024 µg ml−1 and a fractional inhibitory concentration of 64-512 µg ml−1. In mixtures all compounds showed an indifference effect (FIC < 0.15) but chrysin + galangin which was synergistic (FIC = 2.0). Killing curves show a similar behavior as the antibiotic amoxycillin. On the other hand, analyses by transmission electron microscopy at sub inhibitory concentration show vesicle formation and cell lysis after exposition to both individual polyphenol compounds and in mixture. The major compounds of propolis show anti-H. pylori activity both as individual compounds and in mixture. When combined they present mainly indifference but exert a lytic activity upon H. pylori, suggesting a potential bactericidal activity of propolis.

Effects of caffeic acid phenethyl ester on retinal damage after traumatic brain injury / Efectos del ester fenetílico del ácido cafeico en el daño de la retina después de una lesion cerebral traumática

SUMMARY: Head trauma damages the optic nerve visual function and visual acuity.Effects of head trauma on the retina was investigated with biochemical, histological and immunohistochemical respects.The study was conducted on 30 rats with three groups: group 1 was control group (n=10). Second group was head-traumatized group (n=10) and last group was head-traumatized+Caffeic acid phenethyl ester (CAPE, i.p. 20ml/kg/day). Upon head was traumatized, CAPE was applied to trauma+CAPE group and then for the following four days. At the end of 5th day, rats were anesthetized with ketamine hydroxide and then blood samples were taken for biochemical analysis. MDA and GSH-Px values were compared. After blood sample, total eyes of rats were dissected for histopathological and immunohistochemical analysis. In trauma group, degeneration in retinal photoreceptor cells, disintegrity and in inner and outer nuclear layers, hypertrophy in ganglion cells, and hemorrhage in blood vessels were observed. In the group treated with CAPE, lesser degeneration in photoreceptor cells, regular appearances of inner and outer nuclear layers, mild hemorrhage in blood vessels of ganglionic cell layer were observed. The apoptotic changes caused by trauma seen in photoreceptor and ganglionic cells were decreased and cellular organization was preserved due to CAPE treatment. CAPE was thought to induce healing process on traumatic damages.

RESUMEN: El trauma craneal daña la función visual del nervio óptico y la agudeza visual. Se investigaron los efectos del traumatismo craneal en la retina con aspectos bioquímicos, histológicos e inmunohistoquímicos. El estudio se realizó en 30 ratas distribuidas en tres grupos: grupo control (n = 10); grupo con traumatismo craneal (n = 10); grupo con traumatismo craneoencefálico + Éster fenetílico de ácido cafeico (CAPE, i.p. 20 ml / kg / día). Sobre la cabeza traumatizada, se aplicó CAPE a trauma + grupo CAPE durante los siguientes cuatro días. Al final del día 5, las ratas se anestesiaron con hidróxido de ketamina y luego se tomaron muestras de sangre para el análisis bioquímico. Se compararon los valores de MDA y GSH-Px. Después de la muestra de sangre, se disecaron los ojos de las ratas para su análisis histopatológico e inmunohistoquímico. En el grupo de traumatismos, se observó degeneración en las células fotorreceptoras retinianas, desintegridad en capas nucleares internas y externas, hipertrofia en células ganglionares y hemorragia en los vasos sanguíneos. En el grupo tratado con CAPE, se observó una menor degeneración en las células fotorreceptoras, apariciones regulares de capas nucleares internas y externas, hemorragia leve en los vasos sanguíneos de la capa de células ganglionares. Los cambios apoptóticos causados por el trauma visto en el fotorreceptor y las células ganglionares disminuyeron y la organización celular se conservó debido al tratamiento con CAPE. Se concluyó que CAPE induce un proceso de curación en daños traumáticos.

Protective effect of caffeic acid phenethyl ester (CAPE) on ischemia­ reperfusion injury in rat ovary / Efecto protector de ester feniletílico de ácido cafeico (CAPE) en la lesión por isquemia-reperfusión en ovario de rata

The aim of this study was to investigate the effects of caffeic acid phenethyl ester (CAPE) as a prophylactic agent on ischemia/reperfusion (I/R) injury in the rat ovary. A total of 28 Wistar rats were divided into 4 equal groups: (I) sham, (II) ischemia, (III) ischemia + reperfusion, and (IV) IR + CAPE. In groups I and II, ovary torsion was not performed and no drug was administered. In group III, 1 hour of ischemia and 2 hours of reperfusion were performed and no drug was given. Ovarian tissue concentrations of malondialdehyde were significantly higher in the torsion and detorsion groups compared with the sham and Cape groups (P<0.005). The detorsion group showed preantral ovarian follicles and luteal folicules around the blood vessels and positive expression of CD34. In the CAPE group the stromal vascular endothelium with weak expression of CD34 was detected in small areas, and the ovarian follicles and the corpus luteum showed negative expression of CD34. In the study, Biochemical and histopathological results of CAPE treatment was considered to torsion-detorsioned the model showed a protective effect against tissue damage.

El objetivo de este trabajo consistió en investigar los efectos del éster fenetílico del ácido cafeico (EFAC) como agente profiláctico en la lesión por isquemia/reperfusión (I / R) en el ovario de rata. Un total de 28 ratas Wistar se dividieron en 4 grupos iguales: (I) control, (II) isquemia, (III) isquemia + reperfusión, y (IV) IR + EFAC. En los grupos I y II, no se realizó torsión ovárica y no se administró ningún fármaco. En el grupo III, se provocó una hora de isquemia, dos horas de reperfusión y no se administró ningún fármaco. Las concentraciones de malondialdehído en los tejidos ováricos fueron significativamente mayores en los grupos de torsión y de destorsión, en comparación con los grupos sham y de EFAC (P <0,005). El grupo de destorsión mostró folículos ováricos preantrales y folículos lúteos alrededor de los vasos sanguíneos y expresión positiva de CD34. En el grupo EFAC el endotelio vascular estromal con expresión débil de CD34 se detectó en áreas pequeñas, y los folículos ováricos y el cuerpo lúteo mostraron expresión negativa de CD34. En el estudio, fueron considerados los resultados bioquímicos e histopatológicos del tratamiento EFAC en relación a la torsión-destorsión, desarrollando un modelo que mostró un efecto protector contra el daño tisular.

The Radioprotective Effects of Caffeic Acid Phenethyl Ester and Thymoquinone on Oxidative and Nitrosative Stress in Liver Tissue of Rats Exposed to Total Head Irradiation.

OBJECTIVE: The aim of this study is to investigate the effects of addition of caffeic acid phenethyl ester (CAPE) and thymoquinone (TQ) on oxidative and nitrosative stress in the liver tissue of irradiated rats. METHODS: Forty Sprague-Dawley rats were divided into five groups to test the radioprotective effectiveness of TQ and CAPE administered by intraperitoneal injection. Appropriate control groups were also studied. RESULTS: Liver antioxidant capacity, as measured by levels of total superoxide scavenger activity (TSSA), non-enzymatic superoxide scavenger activity (NSSA) and glutathione-S-transferase (GST) activity except superoxide dismutase (SOD) activity, were statistically lower in the irradiation (IR) group compared to all other groups. Total superoxide scavenger activity and NSSA were statistically higher in the IR plus TQ and IR plus CAPE groups compared to all other groups. In contrast, glutathione peroxidase (GSH-Px) activity was significantly found to increase in the IR plus CAPE group compared to control groups. The xanthine oxidase (XO), nitric oxide synthase (NOS) activities, nitric oxide (NO●) and malondialdehyde (MDA) levels in the IR group were statistically higher than in the other groups. Moreover, XO activity in the IR plus TQ group was statistically lower than all other groups including the IR plus CAPE group. In addition, NO● level was found to increase in all groups when compared to the normal control group. CONCLUSIONS: Thymoquinone and CAPE decrease oxidative and nitrosative stress markers and have antioxidant effects, which also increase antioxidant capacity in the liver tissue of irradiated rats.

Estudo da proteção renal durante a isquemia e reperfusão em ratos com o CAPE (caffeic acid phenethyl ester) / A study of kidney protection during ischemia and reperfusion in rats with theCAPE (caffeic acid phenethyl ester)

o CAPE, ativo componente da própolis, é um potente antioxidante com importantes ações no estudo da isquemia e reperfusão renal. O objetivo deste estudo é avaliar o efeito do CAPE na lesão renal de isquemia-reperfusão em ratos anestesiados com isoflurano. Utilizou-se 26 ratos Wistar, machos, com peso superior a 250 g, distribuídos de modo aleatório em três grupos de animais, designados: G1 (controle, isquemia; n = 8); G2 (CAPE + isquemia; n = 10); G3 (diluente do CAPE (etanol) + isquemia; n = 8). Todos os grupos receberam indução da anestesia com isoflurano a 4% e a manutenção com isoflurano de 1,5 a 2,0%. A pressão arterial média (PAM) foi medida para controle da anestesia. A injeção intraperitoneal do CAPE (G2) ou do etanol (G3) foi feita 40 minutos antes da isquemia renal esquerda. Nos três grupos a isquemia durou 25 minutos. Todos os animais foram submetidos à nefrectomia direita. Os valores plasmáticos da creatinina foram determinados no início (M1), no final do experimento (M2) e 24 horas após o final do experimento (M3), quando os animais retornaram ao laboratório e foram anestesiados com isoflurano para coleta de amostra sanguínea e nefrectomia esquerda. Para análise histológica foi utilizada uma escala para avaliação da necrose tubular (0 a 5 = lesão máxima). Houve tratamento estatístico para os valores da temperatura dos animais, peso, PAM, da creatinina plasmática e das lesões histológicas, sendo as diferenças consideradas significantes quando p < 0,05. Conforme mediana, 1o e 3o quartis, entre colchetes, segundo o grupo, a creatinina foi maior em M2 do G2 (0,8 [0,6;0,8]) do que M2 do G1 (0,5[0,4;0,6]) e M2 do G3 (0,6[0,6;0,7]) com p = 0,0012. A creatinina também foi maior em M3 do G2 (3,7 [2,6;4,4]) do que M3 do G1 (0,9[0,7;1,4] e M3 do G3 (1,0[0,9;1,6] com p = 0,0014...

CAPE, an active component of propolis, exhibits antioxidant properties with important actions on ischemia and reperfusion renal study. The purpose of this investigation was to examine the effect of CAPE in renal ischemia/reperfusion in rats anesthetized with isoflurane. Twenty six rats were randomly assigned in three groups: G1 (control, ischemia; n = 8); G2 (CAPE + ischemia; n = 10); G3 (dilute of CAPE (ethanol) + ischemia; n = 8). All groups were anesthetized with isoflurane. Mean arterial pressure (MAP) was monitored for anesthesia control. Intraperitoneal CAPE (G2) or ethanol (G3) injections were realized 40 minutes before left renal ischemia. All animals underwent to right nephrectomy and left kidney was submitted to ischemia for 25 minutes. Serum creatinine values were determined in the beginning (M1) and at the end of experiment (M2) and 24 hours after the experiment (M3) rats were anesthetized with isoflurane and intracardiac blood sample was collected and the left kidney removed for histological analysis, using a scale for tubular necrosis (0-5= injury maximum). Statistical analysis was applied to the values of temperature, weight, MAP, serum creatinine and histological score injury and statistical differences were considered when p<0,05. There were no difference among the temperature of different groups. The weight of G2 were higher than others groups. The PAM of group G3 was higher in M2 than other groups. Creatinine values in M2 of group G2 were higher than M2 of group G1 and M2 of group G3 (p=0.0012) and were higher than M3 of group G1 and M3 of group G3 (p=0.0014). There was no difference of creatinine values in M1 of the three groups (p=0.054)...