Beneficial effects of coconut oil (Cocos nucifera) on hematobiochemicl and histopathological markers in CCL4-intoxicated rabbits / Efeitos benéficos do óleo de coco (Cocos nucifera) em marcadores hematobioquímicos e histopatológicos em coelhos intoxicados com CCL4

The study was designed to investigate the effect of Coconut Oil on the levels of some liver and hematological parameters in carbon tetrachloride intoxicated rabbits. Also the antioxidant capacity of Coconut Oil for various concentrations was assessed on the basis of percent scavenging of (DPPH) free radical. Experimental animals were divided into five groups, eight rabbits in each group. These were: group A (Normal control), group B (Toxic control), group C (Standard control), group D (Treated with Coconut Oil 50 mL/kg body weight after CCl4 intoxication), group E (Treated with Coconut Oil 200 mL/kg body weight after CCl4 intoxication). The effects observed were compared with a standard hepatoprotective drug silymarine (50 mL/kg body weight). The Coconut Oil (200 mL/kg body weight) significantly (P<0.05) reduced the elevated serum levels of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) when compared to a toxic control rabbits. The results of extract treated rabbits were similar to silymarine administered rabbits group. Treatment with Coconut Oil root and silymarine caused no significant changes in RBC, Platelets, (Hb), (MCH) concentration and (HCT) values. However, significant (P<0.05) increase was observed in the total WBC count. The present study suggested that Coconut Oil can be used as an herbal alternative (need further exploration i.e to detect its bioactive compound and its efficacy) for hepatoprotective activit.

O estudo foi desenhado para investigar o efeito do óleo de coco nos níveis de alguns parâmetros hepáticos e hematológicos em coelhos intoxicados com tetracloreto de carbono. Também a capacidade antioxidante do óleo de coco para várias concentrações foi avaliada com base na porcentagem de eliminação de radicais livres (DPPH). Os animais experimentais foram divididos em cinco grupos, oito coelhos em cada grupo. Estes foram: grupo A (controle normal), grupo B (controle tóxico), grupo C (controle padrão), grupo D (tratado com óleo de coco 50 mL/kg de peso corporal após intoxicação por CCl4), grupo E (tratado com óleo de coco 200 mL/kg de peso corporal após intoxicação por CCl4). Os efeitos observados foram comparados com um fármaco hepatoprotetor padrão silimarina (50 mL/kg de peso corporal). O óleo de coco (200 mL/kg de peso corporal) reduziu significativamente (P<0,05) os níveis séricos elevados de alanina transaminase (ALT), aspartato transaminase (AST) e fosfatase alcalina (ALP), quando comparado a um coelho controle tóxico. Os resultados dos coelhos tratados com extrato foram semelhantes aos do grupo de coelhos administrados com silimarina. O tratamento com raiz de óleo de coco e silimarina não causou alterações significativas nos valores de RBC, Plaquetas, (Hb), (MCH) e (HCT). No entanto, observou-se aumento significativo (P<0,05) na contagem total de leucócitos. O presente estudo sugeriu que o óleo de coco pode ser usado como uma alternativa fitoterápica (precisa de mais exploração, ou seja, para detectar seu composto bioativo e sua eficácia) para atividade hepatoprotetora.

A study on the antioxidant activity of rosmarinic acid against carbon tetrachloride-induced liver toxicity in adult male albino rats / Estudio sobre la actividad antioxidante del ácido rosmarínico contra la toxicidad hepática inducida por tetracloruro de carbono en ratas albinas macho adultas

SUMMARY: Carbon tetrachloride (CCl4) is a manufactured chemical and does not occur naturally in the environment. CCl4 is a clear liquid that evaporates very easily. It has a sweet odor. CCl4 is toxic to the mammalian liver and is hepatocarcinogenic in both rats and mice. Rosemary (Rosmarinus Officinalis) is commonly used as a spice and flavoring agent in food processing. It is known for its antioxidant properties. The present study aims to investigate the antioxidant activity of rosmarinic acid (RA) on CCl4-induced liver toxicity in adult male albino rats. Forty adult male albino rats were divided into 4 groups with 10 rats in each group. Group I (control group). Group II animals received RA at a dose of 50 mg/kg/day by oral gavage for 4 weeks. Group III animals received CCl4 intraperitoneally at a dose of 3ml/kg twice weekly for 4 weeks. Group IV animals received CCl4 Plus RA. At the end of the experiment, liver specimens are processed for histological, immunohistochemical, EM and biochemical studies. Administration of RA deceased the elevated serum liver enzymes (AST, ALT, and ALP), elevated MDA level and immunoexpression of the proapoptotic protein (Bax) induced by CCl4. It increased reduced glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and immunoexpression of the antiapoptotic protein (Bcl2). It also improved the histological and ultrastructural changes induced by CCl4. It appears that Rosmarinic acid has protective effects against CCl4-induced hepatotoxicity as indicated by biochemical, histological, immunohistochemical and ultrastructural results.

RESUMEN: El tetracloruro de carbono (CCl4) es un producto químico fabricado y no se encuentra de forma natural en el medio ambiente. CCl4 es un líquido transparente que se evapora fácilmente; tiene un olor dulce. CCl4 es tóxico para el hígado de los mamíferos y es hepatocarcinogénico tanto en ratas como en ratones. El romero (Rosmarinus officinalis) se usa comúnmente como condimento y agente aromatizante en el procesamiento de alimentos. Es conocido por sus propiedades antioxidantes. El presente estudio tuvo como objetivo investigar la actividad antioxidante del ácido rosmarínico (RA) sobre la toxicidad hepática inducida por CCl4 en ratas albinas macho adultas. Se dividieron cuarenta ratas albinas macho adultas en 4 grupos con 10 ratas en cada grupo. Grupo I (grupo control). Los animales del grupo II recibieron AR a una dosis de 50 mg / kg / día por sonda oral durante 4 semanas. Los animales del grupo III recibieron CCl4 por vía intraperitoneal a una dosis de 3 ml / kg dos veces por semana durante 4 semanas. Los animales del grupo IV recibieron CCl4 Plus RA. Al final del experimento, las muestras de hígado se procesaron para estudios histológicos, inmunohistoquímicos, EM y bioquímicos. La administración de AR eliminó las enzimas hepáticas séricas elevadas (AST, ALT y ALP), el nivel elevado de MDA y la inmunoexpresión de la proteína proapoptótica (Bax) inducida por CCl4. Aumentó el glutatión reducido (GSH), glutatión peroxidasa (GSH-Px), la superóxido dismutasa (SOD) y la inmunoexpresión de la proteína antiapoptótica (Bcl2). También mejoró los cambios histológicos y ultraestructurales inducidos por CCl4. El ácido rosmarínico puede tener efectos protectores contra la hepatotoxicidad inducida por CCl4, tal como lo indican los resultados bioquímicos, histológicos, inmunohistoquímicos y ultraestructurales.

Acutely applied melatonin prevents CCl4-induced testicular lesions in rats: the involvement of the oxidative capacity and arginine metabolism

Abstract Carbon tetrachloride (CCl4) represents an organic chemical that causes reactive oxygen species derived organ disturbances including male infertility. Melatonin (MLT) is a neurohormone with strong antioxidant capacity, involved in numerous physiological processes. In this study we evaluated the capability of MLT, administered in a single dose of 50 mg/kg, to preserve the testicular tissue function after an acute administration of CCl4 to rats. The disturbance in testicular tissue and the effects of MLT after CCl4 exposure were estimated using biochemical parameters that enabled us to determine the tissue (anti)oxidant status and the intensity of arginine/nitric oxide metabolism. Also, the serum levels of testosterone and the histopathological analysis of tissue gave us a better insight into the occurring changes. A significant diminution in tissue antioxidant defences, arginase activity and serum testosterone levels, followed by the increased production of nitric oxide and extensive lipid and protein oxidative damage, was observed in the CCl4-treated group. The application of MLT after the CCl4 caused changes, clearly visible at both biochemical and histological level, which could be interpreted mainly as a consequence of general antioxidant system stimulation and a radical scavenger. On the other hand, the application of MLT exerted a limited action on the nitric oxide signalling pathway.

In vivo protective effect of cinnamon aqueous extract in carbon tetrachloride-treated male albino rats

The liver as an organ is important for the metabolism of drugs and toxins. However, it is not immune from environmental insults. Exposure of liver cells to carbon tetrachloride (CCl4) results in the generation of tricholoromethyl radicals, which induce liver toxicity. This study aims at investigating the ameliorative effect of the cinnamon aqueous extract (CAE) against CCl4-induced hepatotoxicity in male albino rats. Hepatotoxicity was induced in rats through the intraperitoneal administration of 0.5 mL kg-1body weight of CCl4. The analyses of the results obtained showed significant reduction in the levels of serum biochemical markers for 400 and 600 mg kg-1bw of CAE protected rats as compared with CCl4group. In addition, CAE administration reversed liver tissue damaged via increased antioxidants markers. Histopathological examination of CAE treatment on rats showed improved changes to the liver damage caused by CCl4 with no evidence of steatosis and inflammation. This result hence suggests that CAE has marked hepatoprotective and healing activities against CCl4-induced liver damage and could serve as a suitable candidate in drug discovery for the treatment of liver toxicity.

Esteatose hepática altera acúmulo celular em tilápias do Nilo durante aerocistite infecciosa / Hepatic steatosis alters cellular recruitment during induced aerocystitis in Nile tilapia

O presente estudo avaliou a hepatotoxicidade induzida pelo CCl4 durante o efeito glicocorticoide da dexametasona (DEX) na fisiopatologia da reação inflamatória aguda em tilápias do Nilo, Oreochromis niloticus, correlacionando a funcionalidade hepática à cinética de acúmulo celular em aerocistite infecciosa. Para tal, utilizou-se 84 tilápias do Nilo distribuídas em 4 tratamentos: controle, CCl4, DEX e CCl4+DEX. Sendo amostrados 7 animais por tratamento em três períodos, isto é: seis, 24 e 48h após indução de inflamação. Utilizou-se CCl4 em dose única de 0,5mL/kg, via intraperitoneal para causar o transtorno hepático. Para indução da aerocistite utilizou-se inóculo de Aeromonas hydrophila. A dexametasona foi administrada via intramuscular na dose de 2 mg/kg de peso vivo. Os resultados revelaram que quanto maior foi à atividade sérica de aspartato aminotransferase (AST) maior foi a alteração somática do fígado, sendo estes achados inversamente proporcionais ao acúmulo celular no foco inflamatório, demonstrando menor número de células inflamatórias nos animais acometidos com maior grau de distúrbios hepáticos induzidos pelo CCl4. O estudo histopatológico revelou alterações degenerativas transitórias na fase mais aguda, pois os fígados das tilápias revelaram o acúmulo lipídeos nos hepatócitos 6h após administração de CCl4, sendo esta degeneração gordurosa não mais observada nos tempos de 24 e 48h. Contudo, a administração de CCl4 em tilápias do Nilo resultou em degeneração hepática aguda e transitória, caracterizada pelo acúmulo de gordura nos hepatócitos, aumento de AST no sangue e hepatomegalia. Com a disfunção hepática houve comprometimento do recrutamento celular em aerocistite infecciosa, indicando que há participação do fígado na resposta imune inata em peixes.(AU)

The study evaluated the hepatotoxicity induced by CCl4 during the glucocorticoid effect of dexamethasone (DEX) on the pathophysiology of the acute inflammatory reaction in Nile tilapia, Oreochromis niloticus, correlating hepatic functionality with cellular accumulation kinetics in infectious aerocystitis. Eighty- four Nile tilapia were distributed into four treatments: control, CCl4, DEX and CCl4 + DEX. Seven tilapia were sampled per treatment in three periods: 6, 24 and 48h after induction of inflammation. CCl4 was used in a single dose of 0.5mL/kg intraperitoneally to cause hepatic disorder. Aeromonas hydrophila inoculum was used to induce aerocystitis. Dexamethasone was administered intramuscularly at the dose of 2mg/kg b. w. The results revealed a higher serum aspartate transaminase (AST) activity associated with greater somatic liver alteration, being these findings inversely proportional to the cellular accumulation in the inflammatory focus, demonstrating a lower number of inflammatory cells in the animals affected with a higher degree of hepatic disorders induced by CCl4. The histopathological study revealed transient degenerative changes in the most acute phase, as livers of tilapia showed accumulation of lipids in hepatocytes 6 hours after administration of CCl4, and this fatty degeneration was no longer observed in 24 and 48h. However, administration of CCl4 in Nile tilapia resulted in acute and transient liver degeneration, characterized by accumulation of fat in hepatocytes, increased AST in the blood and hepatomegaly. With liver dysfunction there was compromise of cellular recruitment in infectious aerocystitis, indicating that there is liver involvement in the innate immune response in tilapia.(AU)

Stereological assessment of nephroprotective effects of Trachyspermum ammi essential oil against carbon tetrachloride-induced nephrotoxicity in mice / Evaluación estereológica de los efectos nefroprotectores del aceite esencial de Trachyspermum ammi contra la nefrotoxicidad inducida por tetracloruro de carbono en ratones

Trachyspermum ammi (T. ammi) has been used in folk medicine as anti-inflammatory, antipyretic, antibacterial, antifungal agent. The present study was conducted to investigate the protective effect of Trachyspermum ammi (T. ammi) essential oil against CC14- induced nephrotoxicity in mice. Thirty-five mice were divided into five groups as follows; positive control received olive oil 1 mL/ kg/ip, negative control received CC14 1 mg/kg/ip + 0.5 mL distilled water orally and tree treatment groups which received CC14 similar to the negative control and 200, 800 and 1600 µg/kg of T. ammi essential oil, respectively. All treatments were done twice a week (Saturday and Wednesday) for 45 days. On the last day, blood was sampled for urea and creatinine assessment and the left kidney was removed for stereological estimations. Essential oil of T. ammi at high dose significantly (p ≤ 0.05) decreased serum levels of creatinine and urea in comparison with CC14-treated group. Total volume of the kidney, cortex, proximal convoluted tubules (PC), glomerulus, vessels and interstitial tissue as well as total length of PC and vessel were significantly (p ≤ 0.05) increased following CC14 administration and were restored toward normal levels at high dose of T. ammi. Also, high dose of T. ammi improved glomerular loss significantly (p ≤ 0.05) as compared with CC14-treated group. Due to the chemical composition of T. ammi essential oil such as tymol, p-cymene, γ-terpinene which are antioxidant, it can be concluded that the essential oil of T. ammi can ameliorated renal injury induced following CC14 toxicity via its antioxidant components.

En la medicina popular se ha utilizado el aceite esencial de Trachyspermum ammi (T. ammi) como agente antiinflamatorio, antipirético, antibacteriano y anti fúngico. El presente estudio se realizó para investigar el efecto protector de Trachyspermum ammi (T. ammi) aceite esencial contra la nefrotoxicidad inducida en ratones. Treinta y cinco ratones fueron divididos en cinco grupos de la siguiente manera; el control positivo recibió 1 mL / kg / ip de aceite de oliva, el control negativo recibió 1 mg / kg / ip + 0,5 mL de agua destilada por vía oral y grupos de tratamiento arbóreo que recibieron un control similar al negativo y 200, 800 y 1600 mg / kg de T. aceite esencial de T. ammi, respectivamente. Todos los tratamientos se realizaron dos veces por semana (sábado y miércoles) durante 45 días. En el último día de tratamiento, se tomaron muestras de sangre para evaluar la urea y la creatinina, y se extrajo el riñón izquierdo para realizar estimaciones estereológicas. El aceite esencial de T. ammi a dosis altas significativamente (p ≤ 0,05) disminuyó los niveles séricos de creatinina y urea en comparación con el grupo tratado. El volumen total del riñón, la corteza, los túbulos contorneados proximales (PC), el glomérulo, los vasos y el tejido intersticial, así como la longitud total de la PC y el vaso aumentaron significativamente (p ≤ 0,05) después de la administración y se restablecieron a niveles normales con dosis altas de T. ammi. Además, una dosis alta de T. ammi mejoró significativamente la pérdida glomerular (p ≤ 0,05) en comparación con el grupo tratado. Debido a la composición química del aceite esencial de T. ammi como timol, p-cimeno, 𝛾-terpineno con propiedades antioxidantes, se puede concluir que el aceite esencial de T. ammi puede mejorar la lesión renal inducida después de la toxicidad a través de sus componentes antioxidantes.

Swertiamarin attenuates carbon tetrachloride (CCl4)-induced liver injury and inflammation in rats by regulating the TLR4 signaling pathway

The aim of the present study is to illustrate the effects of swertiamarin (STM), a natural iridoid from herbal medicines, on hepatic inflammation induced by carbon tetrachloride (CCl4) in rats. Male Sprague Dawley rats were exposed to CCl4 with or without STM co-administration for 8 weeks. Our results revealed that STM administration (100 and 200 mg/kg b.w.) significantly attenuated inflammation in livers of CCl4-treated rats. STM remarkably reduced the production of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein-1a (MIP-1α), and monocyte chemotactic protein-1 (MCP-1) in liver tissue of CCl4-treated rats. In addition, STM treatment downregulated connective tissue growth factor (CTGF) and ser307pIRS-1 expression, which was induced by CCl4 exposure. In the process of exploring the anti-inflammatory mechanisms of STM action, we demonstrated that STM significantly inhibited Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65 expression in the liver. In conclusion, these results suggested that the inhibition of CCl4-induced inflammation by STM was, at least in part, due to its regulation of the TLR4 /NF-κB signaling pathway

Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment

OBJECTIVES: The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated. METHODS: The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression. RESULTS: CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice. CONCLUSION: Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice.

Efecto hepatoprotector de una mezcla de siete plantas en cirrosis inducida con tetracloruro de carbono / Hepatoprotective effect of a mixture of seven plants in carbon tetrachloride induced cirrhosis

Introducción: las plantas medicinales han sido utilizadas con fines terapéuticos desde tiempos antiguos sobre diversas enfermedades, en este sentido, se han reportado por la medicina tradicional una gran variedad de plantas con actividad gastrointestinal y efecto hepatoprotector. Las plantas utilizadas en este estudio fueron Bidens odorata Cav. L., Tecoma stans L., Equisetum hyemale L., Rosmarinus officinalis L., Cynaya scolymus L., Peumus boldus L. y Linum usitatissimum L. Objetivo: demostrar el efecto hepatoprotector de una mezcla de siete plantas (EHAM7) en ratas cirróticas inducidas con tetracloruro de carbono (CCl4). Métodos: se utilizaron las semillas de L. usitatissimum y las hojas y flores secas del resto de las plantas. Se formaron grupos de ratas control y ratas cirróticas con y sin tratamiento con la mezcla. A los animales cirróticos se les indujo el daño hepático intraperitonealmente con 0,2 mL de una mezcla de CCl4 y aceite mineral. Por otra parte, se les administraron oralmente 200 mg/kg del EHAM 7 re-suspendido en solución salina durante una semana y posteriormente cada tercer día durante ocho semanas. Los animales fueron sacrificados y se determinó el perfil hepático (transaminasas, bilirrubina y proteínas) y lipídico (triglicéridos, colesterol y lipoproteínas) en muestras de suero sanguíneo; el hígado se utilizó para los estudios histológicos. Resultados: el EHAM7 mostró efecto hepatoprotector en los animales cirróticos sobre los parámetros séricos correspondientes al perfil hepático y al perfil lipídico, lo cual se correlaciona con las características histológicas del hígado. Conclusión: el EHAM7 presenta efecto hepatoprotector en ratas cirróticas inducidas con CCl4, debido a que dicha mezcla presenta compuestos polifenólicos con actividad antioxidante(AU

Introduction: Medicinal plants have been used for therapeutic purposes against a great variety of diseases since ancient times. A large number of plants with gastrointestinal activity and hepatoprotective effect have been used in traditional medicine. The plants examined in the present study were Bidens odorata Cav. L., Tecoma stans L., Equisetum hyemale L., Rosmarinus officinalis L., Cynaya scolymus L., Peumus boldus L. and Linum usitatissimum L. Objective: Demonstrate the hepatoprotective effect of a mixture of seven plants (EHAM7) in carbon tetrachloride (CCl4) induced cirrhotic rats. Methods: The study used seeds of L. usitatissimum and dry flowers and leaves of the remaining plants. Groups were formed of control and cirrhotic rats with and without treatment with the mixture. Hepatic damage was induced intraperitoneally into the cirrhotic animals with 0.2 ml of a mixture of CCl4 and mineral oil. The rats were also administered 200 mg/kg EHAM7 resuspended in saline solution orally during a week and then every third day during eight weeks. The animals were sacrificed and determination was made of the hepatic profile (transaminases, bilirubin and proteins) and lipid profile (triglycerides, cholesterol and lipoproteins) in blood serum samples. The liver was preserved for histological examination. Results: EHAM7 was found to have an hepatoprotective effect on the serum parameters corresponding to the hepatic and lipid profiles of cirrhotic animals, which correlates with the histological characteristics of the liver. Conclusion: EHAM7 has a hepatoprotective effect in CCl4 induced cirrhotic rats, since the mixture contains polyphenolic compounds with antioxidant activity(AU)

Avaliação físico-química de óleos da amêndoa de pequi ( Caryocar brasiliense Camb. ) obtidos artesanalmente e por prensagem a frio e sua influência sobre marcadores bioquímicos, oxidativos e inflamatórios de ratos submetidos à toxicidade aguda por tetracloreto de carbono / Evaluation of physical-chemistry properties of handmade and cold-pressed pequi ( Caryocar brasiliense Camb. ) almond oil and its influence on biochemical, oxidative and inflammatory markers in rats subjected to carbon tetrachloride-induced acute toxicity

O óleo da amêndoa de pequi (Caryocar brasiliense Camb.) é considerado um coproduto do fruto, consumido na região do Cerrado, bioma brasileiro. Ele é fundamental para agregar valor e ampliar a utilização deste fruto regional a outros setores produtivos comerciais. Relatos na literatura apontam que o óleo possui capacidade antioxidante e efeitos benéficos sobre doenças inflamatórias, que estão associados à presença de ácidos graxos insaturados e fitoquímicos em sua composição química. Por outro lado, o tetracloreto de carbono (CCl4) é uma potente hepatotoxina, capaz de gerar radicais livres que levam ao estresse oxidativo e à inflamação. Nesse contexto, o objetivo do presente estudo foi caracterizar os óleos da amêndoa de pequi obtidos artesanalmente e por prensagem a frio e verificar o efeito de seus constituintes graxos e bioativos sobre parâmetros oxidativos e inflamatórios de ratos submetidos à toxicidade aguda induzida por tetracloreto de carbono. Inicialmente, foram investigados os parâmetros de qualidade dos óleos, bem como o perfil de ácidos graxos, teores de compostos bioativos, capacidade antioxidante e estabilidade termo-oxidativa. Os óleos da amêndoa de pequi apresentaram boa qualidade e resistência termo-oxidativa e mostraram-se ricos em ácido graxo oleico, além de possuírem compostos com propriedades antioxidantes, como fenólicos, carotenoides, tocoferóis e fitosteróis. Posteriormente, o efeito do tratamento por 22 dias com óleos da amêndoa de pequi artesanal ou prensado a frio (3 mL/kg) sobre a toxicidade aguda induzida pelo CCl4 em ratos "Wistar" machos foi avaliado. Para tal, foram determinados marcadores bioquímicos séricos, perfil lipídico, peroxidação lipídica, marcadores do sistema de defesa antioxidante e detoxificante, além de parâmetros inflamatórios do tecido hepático. De maneira geral, verificou-se que os óleos da amêndoa de pequi não minimizaram as alterações hepáticas induzidas pelo CCl4, evidenciadas pelas enzimas marcadoras do dano hepático e por parâmetros inflamatórios, no entanto os animais tratados com o óleo prensado a frio aumentaram sua capacidade antioxidante

The pequi (Caryocar brasiliense Camb.) almond oil is considered a by-product of the fruit, consumed in the Brazilian savannah region. It is essential to add value and increase the use this regional fruit to other commercial productive sectors. The pequi almond oil has been reported to possess antioxidant capacity and beneficial effect on inflammatory diseases due its chemical composition in unsaturated fatty compounds and phytochemicals. On the other hand, the carbon tetrachloride (CCl4) is a potent hepatotoxin that is capable of generating free radicals and lead to oxidative stress and inflammation. In this context, the aim of this study was to characterize the pequi almond oils obtained by handmade and cold-press process and verify the effect of their fatty acids and bioactive constituents on oxidative and inflammatory parameters in rats submitted to carbon tetrachloride-induced acute toxicity. Initially, quality parameters, chemical composition and thermo-oxidative stability of the oils were investigated. The pequi almond oils showed good quality and thermo-oxidative resistance and shown to be rich in oleic fatty acid, besides the presence of compounds with antioxidant properties, such as phenolics, carotenoids, tocopherols and phytosterols. Subsequently, the effect of the oils (3 mL/kg) treatment for 22 days on acute toxicity induced by CCl4 in male Wistar rats was evaluated. The serum biochemical markers levels, lipid profile, lipid peroxidation, markers of antioxidant defense and detoxication and inflammatory parameters in liver tissue were determined. In general, it was found that the pequi almond oil not minimized liver alterations induced by CCl4, as evidenced by the liver function enzymes and the inflammatory parameters, however in animals which received the cold pressed oil was increased antioxidant capacity

Percepção dos idosos jovens e longevos gaúchos quanto aos espaços públicos em que vivem / The perception of the young and long-lived elderly ‘Gauchos’ (from the State of Rio Grande do Sul, Brazil) about the public spaces they live in Resumo

Em 2050, o número de brasileiros residindo em áreas urbanas passará dos 200 milhões e 29% da população será composta por idosos. Os idosos longevos possuem 80 anos ou mais, os idosos jovens são aqueles que apresentam idade entre 60 e 79 anos. O objetivo foi verificar a diferença da percepção de idosos jovens e longevos do Rio Grande do Sul quanto ao ambiente urbano em que vivem. Estudo de base populacional, observacional, descritivo, retrospectivo, com paradigma de análise quantitativa, analisou dados da pesquisa Perfil dos Idosos do RS, realizado pelo Instituto de Geriatria e Gerontologia da PUCRS em parceria com a Escola de Saúde Pública do RS. A amostra foi composta por 6913 questionários respondidos por idosos de 59 cidades. A análise dos dados foi realizada com cada um dos grupos etários e as variáveis independentes foram testadas pelo Qui-Quadrado, sendo o nível de significância menor que 0,05. Como resultado, a percepção de dificuldades, como poucos bancos, falta de faixas de segurança, tempo de sinal muito curto para pedestres, degraus muito altos e mau cheiro dos banheiros públicos, foi maior entre os idosos jovens. Os idosos longevos perceberam menos esses fatores, porém, referiram que frequentam menos os ambientes comunitários.

By 2050, the number of Brazilians living in urban areas will be over 200 million and 29% of the population will be elderly. The long-lived elderly are 80 or more years old and the young elderly are between 60 and 79 years of age. The scope of this article was to verify the difference in perception between the young elderly and the long-lived elderly from Rio Grande do Sul (RS) about the urban environment they live in. This is a population-based, observational, descriptive, retrospective study with a quantitative analysis paradigm. Data was analyzed from Elderly Profile research in RS conducted by the Geriatric and Gerontological Institute of PUCRS in partnership with the RS School of Public Health. The sample consisted of 6913 questionnaires answered by the elderly from 59 cities. Data analysis was performed for each age group and independent variables were processed using the Chi-square test, with p under 0.05. Results showed that the perception of difficulties such as a lack of park benches and safety strips, short traffic light times for pedestrians, high steps and bad-smelling public toilets was greater among the young elderly. The long-lived elderly noticed these facts less, though they admitted that they frequent community environments less often.

International cooperation Brazil-Cuba-Haiti: the role of community radios in strengthening social mobilization in the public health context in Haiti / Cooperação internacional Brasil-Cuba-Haiti: o papel das rádios comunitárias no fortalecimento da mobilização social no âmbito da saúde pública no Haiti

The present article investigates the role of Haitian community radios in strengthening social mobilization, with the aim of supporting the actions undertaken in the field of public health in Haiti, based on the development of the Workshop for community radios, as part of the Tripartite Cooperation Brazil-Cuba-Haiti. The qualitative methodology is justified because of the study content, an analysis of documents and direct observation, through a case study presented at the Workshop held in the department of Hinches, in Haiti. This meeting was held in the context of the Working Group on Tripartite Communication, under the responsibility of the Health Channel/Fiocruz, in partnership with the Department for Health Promotion and Environmental Prevention of the Ministry of Health and Population of Haiti (DPSPE/MSPP/Haiti), with a proposal to better structure a network of multipliers in health promotion.

O presente artigo investiga o papel das rádios comunitárias haitianas no fortalecimento da mobilização social com a finalidade de subsidiar as ações empreendidas no campo da saúde pública no Haiti a partir da construção e do desenvolvimento da Oficina para rádios comunitárias, no âmbito da Cooperação Tripartite Brasil-Cuba-Haiti. A metodologia de cunho qualitativo justifica-se pelo teor do estudo, de análise de documentos e da observação direta, mediante estudo de caso a partir da Oficina, realizada no departamento de Hinches, no Haiti. O encontro foi realizado no âmbito do Grupo de Trabalho de Comunicação da Tripartite, sob a responsabilidade do Canal Saúde/Fiocruz, em parceria com o Departamento de Promoção da Saúde e Prevenção do Meio Ambiente do Ministério da Saúde e População do Haiti (DPSPE/MSPP/Haiti), com a proposta de estruturar uma rede de multiplicadores de promoção da saúde.

Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in rats

BACKGROUND: Carbon tetrachloride (CCl4) induces hepatotoxicity in animal models, including the increased blood flow and cytokine accumulation that are characteristic of tissue inflammation. The present study investigates the hepato-protective effect of rutin on CCl4-induced hepatotoxicity in rats. RESULTS: Forty male Wistar rats were divided into four groups. Group I (control group) received 1 mL/kg of dimethyl sulfoxide intragastrically and 3 mL/kg olive oil intraperitoneally twice a week for 4 weeks. Group II received 70 mg/ kg rutin intragastrically. Groups III and IV received CCl4 (3 mL/kg, 30 % in olive oil) intraperitoneally twice a week for 4 weeks. Group IV received 70 mg/kg rutin intragastrically after 48 h of CCl4 treatment. Liver enzyme levels were determined in all studied groups. Expression of the following genes were monitored with real-time PCR: interleukin-6 (IL-6), dual-specificity protein kinase 5 (MEK5), Fas-associated death domain protein (FADD), epidermal growth factor (EGF), signal transducer and activator of transcription 3 (STAT3), Janus kinase (JAK), B-cell lymphoma 2 (Bcl2) and B-cell lymphoma-extra-large (Bcl-XL). The CCl4 groups showed significant increases in biochemical markers of hepatotoxicity and up-regulation of expression levels of IL-6, Bcl-XL, MEK5, FADD, EGF, STAT3 and JAK compared with the control group. However, CCl4 administration resulted in significant down-regulation of Bcl2 expression compared with the control group. Interestingly, rutin supplementation completely reversed the biochemical markers of hepatotoxicity and the gene expression alterations induced by CCl4. CONCLUSION: CCl4 administration causes alteration in expression of IL-6/STAT3 pathway genes, resulting in hepatotoxicity. Rutin protects against CCl4-induced hepatotoxicity by reversing these expression changes.

Cytotoxicity and hepatoprotective attributes of methanolic extract of Rumex vesicarius L

BACKGROUND: To evaluate the hepatoprotective potential and invitro cytotoxicity studies of whole plant methanol extract of Rumex vesicarius L. Methanol extract at a dose of 100 mg/kg bw and 200 mg/kg bw were assessed for its hepatoprotective potential against CCl4-induced hepatotoxicity by monitoring activity levels of SGOT (Serum glutamic oxaloacetic transaminase), SGPT (Serum glutamic pyruvic transaminase), ALP (Alkaline phosphatase), TP (Total protein), TB (Total bilirubin) and SOD (Superoxide dismutase), CAT (Catalase), MDA (Malondialdehyde). The cytotoxicity of the same extract on HepG2 cell lines were also assessed using MTT assay method at the concentration of 62.5, 125, 250, 500 µg/ml. RESULTS: Pretreatment of animals with whole plant methanol extracts of Rumex vesicarius L. significantly reduced the liver damage and the symptoms of liver injury by restoration of architecture of liver. The biochemical parameters in serum also improved in treated groups compared to the control and standard (silymarin) groups. Histopathological investigation further corroborated these biochemical observations. The cytotoxicity results indicated that the plant extract which were inhibitory to the proliferation of HepG2 cell line with IC50 value of 563.33 ± 0.8 Mg/ml were not cytotoxic and appears to be safe. CONCLUSIONS: Rumex vesicarius L. whole plant methanol extract exhibit hepatoprotective activity. However the cytotoxicity in HepG2 is inexplicable and warrants further study.

Use and records of child health handbook focused on growth and development / Uso y llenado de la libreta de salud infantil con el foco en el crecimiento y el desarrollo / Uso e preenchimento da caderneta de saúde da criança com foco no crescimento e desenvolvimento

Objective To evaluate the use and records of the Child Health Handbook (CHH), especially growth and development. Method Cross-sectional study with 358 mother-child pairs registered in 12 Primary Health Centers (PHCs) of a small municipality. Mothers were interviewed at the PHC from February to April 2013 using a questionnaire. Data analysis was done using WHO Anthro software, Epi InfoTM and Stata. Results Fifty-three percent of the mothers were carrying the CHH at the time of the interview, similar to the proportion of mothers who were instructed to bring the CHH to health appointments. Annotations in the CHH during the visits were reported by 49%. The vaccination schedule was completed in 97% of the CHH, but only 9% and 8% of the CHH, respectively, contained growth charts and properly completed developmental milestones. Conclusion Low rates of use and unsatisfactory record-keeping in the CHH reinforce the need for investment in professional training and community awareness for the CHH to become an effective instrument of promotion of child health. .

Objetivo Evaluar el uso y llenado de la Libreta de Salud Infantil (LSI), especialmente el crecimiento y el desarrollo. Método Estudio transversal con 358 pares de madres e hijos matriculados en 12 Unidades Básicas de Salud (UBS) de una ciudad pequeña. Las madres fueron entrevistadas en el UBS desde febrero a abril 2013 mediante un cuestionario. Se utilizó Epi-info y software SPSS. Resultados 53% de las madres estaban llevando LSI durante la entrevista, proporción similar a las madres que recibieron instrucciones para llevar el LSI a la atención de la salud. Anotaciones en LSI durante las visitas se registraron en un 49%. Calendario de vacunas fue completa en el 97% de LSI, pero sólo el 9% y el 8% de LSI tenido, respectivamente, las curvas de crecimiento y desarrollos debidamente cumplimentados. Conclusión El uso y el relleno satisfactorio de LSI refuerzan la necesidad de inversión en la formación profesional y el acercamiento a la comunidad para la LSI se convierte efectivamente en un instrumento de promoción de la salud infantil.
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Objetivo Avaliar uso e preenchimento da Caderneta de Saúde da Criança (CSC), especialmente crescimento e desenvolvimento. Método Estudo transversal com 358 pares mãe-criança atendidos em 12 Unidades Básicas de Saúde (UBS) de município de pequeno porte. As mães foram entrevistadas nas UBS, de fevereiro a abril de 2013, com o uso de questionário. Utilizou-se softwares Epi-info e Stata. Resultados No momento da entrevista, 53% das mães portavam a CSC, proporção similar à de mães que referiram orientação para levar a CSC aos atendimentos de saúde. Anotações na CSC durante os atendimentos foram referidos por 49%. Esquema vacinal estava completo em 97% das CSC, mas apenas 9% e 8% das CSC tinham, respectivamente, gráficos de crescimento e desenvolvimento adequadamente preenchidos. Conclusão O uso e o preenchimento insatisfatório da CSC reforçam a necessidade de investimentos na capacitação dos profissionais e na sensibilização da comunidade para que a CSC se torne efetivamente um instrumento de promoção da saúde infantil. .

Protective effect of bixin on carbon tetrachloride-induced hepatotoxicity in rats

BACKGROUND: The liver is an important organ for its ability to transform xenobiotics, making the liver tissue a prime target for toxic substances. The carotenoid bixin present in annatto is an antioxidant that can protect cells and tissues against the deleterious effects of free radicals. In this study, we evaluated the protective effect of bixin on liver damage induced by carbon tetrachloride (CCl4) in rats. RESULTS: The animals were divided into four groups with six rats in each group. CCl4 (0.125 mL kg-1 body wt.) was injected intraperitoneally, and bixin (5.0 mg kg-1 body wt.) was given by gavage 7 days before the CCl4 injection. Bixin prevented the liver damage caused by CCl4, as noted by the significant decrease in serum aminotransferases release. Bixin protected the liver against the oxidizing effects of CCl4 by preventing a decrease in glutathione reductase activity and the levels of reduced glutathione and NADPH. The peroxidation of membrane lipids and histopathological damage of the liver was significantly prevented by bixin treatment. CONCLUSION: Therefore, we can conclude that the protective effect of bixin against hepatotoxicity induced by CCl4 is related to the antioxidant activity of the compound.

Lung and liver hhanges due to the induction of cirrhosis in two experimental models / Alteracoes hepaticas e pulmonares decorrentes da inducao de cirrose em dois modelos experimentais.

Context To evaluate lung and liver changes in two experimental models using intraperitoneal carbon tetrachloride (CCl4) and bile duct ligation (BDL). Methods Twenty-four male Wistar rats were divided into a control group (CO) and an experimental group (EX). We evaluated the liver transaminases (AST, ALT, AP), arterial blood gases (PaO2, PCO2 and SpO2) and lipid peroxidation by TBARS (substances that react to thiobarbituric acid) and chemiluminescence. We also evaluated the antioxidant enzyme superoxide dismutase (SOD) and histology of lung tissue and liver. Results There were significant differences in AST, ALT, ALP and PaO2 between CO group and EX group (P<0.05). The levels of TBARS, chemiluminescence and activity of enzyme superoxide dismutase were increased to different degrees in the CCl4 groups: CO and in the BDL -EX (P<0.05, respectively). In the lung histology, an increase in the wall thickness of the pulmonary artery and a diameter reduction in the CCl4 animal model were observed: comparing CO group with EX group, we observed a reduction in thickness and an increase in the diameter of the artery wall lung. Conclusion Both experimental models have caused liver damage and alterations in the artery wall that are associated with major changes in pulmonary gas exchange. .

Objetivo Avaliar as alterações pulmonares e hepáticas em dois modelos experimentais de cirrose hepática pelo uso de tetracloreto de carbono intraperitoneal (CCl4) e ligadura de ducto biliar. Métodos Vinte e quatro ratos machos Wistar foram divididos em grupo controle (CO) e experimental (EX). Foram avaliadas as transaminases hepáticas (AST, ALT, FA), gasometria arterial (PaO2, PCO2 e SatO2) e a lipoperoxidação através de TBARS (substâncias que reagem ao ácido tiobarbitúrico) e por quimiluminescência. Também foi avaliada a atividade antioxidante da enzima superóxido dismutase e a histologia do tecido pulmonar e hepático. Resultados Nas enzimas hepáticas (AST, ALT e FA), bem como na PaO2 foram observadas diferenças significativas (P≤0,05) entre os grupos CO vs EX em ambos modelos. Os níveis de TBARS, quimiluminescência e a atividade da enzima superóxido dismutase encontram-se aumentados nos grupos CCl4 e ligadura de ducto biliar: CO vs EX (P≤0,05). Na análise histológica do pulmão observamos um aumento na espessura da parede da artéria pulmonar e uma redução no diâmetro no modelo CCl4: CO vs EX, e no modelo de ligadura de ducto biliar podemos observar uma redução da espessura e aumento no diâmetro da parede da artéria pulmonar. Conclusão Ambos os modelos experimentais provocaram dano hepático, além de causar alterações na parede da artéria pulmonar contribuindo na redução das trocas gasosas. .

Efecto de Noni C sobre el daño hepático inducido por tetracloruro de carbono en ratas / Effect of Noni C on the carbon tetrachloride-induced hepatic damage in rats

Introducción: las enfermedades hepáticas son un serio problema de salud. El estudio de agentes de origen natural que disminuyan el daño hepático inducido por sustancias químicas ha despertado un interés especial. Objetivo: evaluar el efecto del Noni C sobre el daño hepático inducido por tetracloruro de carbono, en modelo experimental desarrollado en ratas Wistar machos. Métodos: se realizó estudio experimental y se usó como control positivo el tetracloruro de carbono a dosis de 0,3 mL/kg de peso, intraperitoneal, durante 3 días; y como control negativo solución salina. Se utilizaron 4 dosis (85, 130, 170 y 215 mg/kg de peso) de Noni C durante 6 días, postratamiento con tetracloruro de carbono. Se determinaron niveles de transaminasa glutámico pirúvica y glutámico oxalacética; también lesión hepática como tumefacción celular, hepatitis reactiva, esteatosis y necrosis. Resultados: se obtuvo reducción significativa de las transaminasas glutámico pirúvica y glutámico oxalacética a las dosis de 85 y 170 mg/kg de Noni C, y ausencia de necrosis y esteatosis en los grupos tratados con las dosis de 170 y 215 mg/kg de peso. Conclusiones: en los grupos tratados con Noni C disminuyó el daño hepático inducido por el tetracloruro de carbono

Introduction: liver diseases are a serious health problem. The study of natural agents that can reduce the chemical substance-induced hepatic damage has aroused a particular interest. Objective: to evaluate the effect of Noni C on the carbon tetrachloride-induced hepatic damage in an experimental model developed in male Wistar rats. Methods: An experimental study was conducted in which the positive control was carbon tetrachloride at a dose of 0.3 mL/kg of weight, intraperitoneally administered for 3 days, and the negative control was saline solution. Four doses of Noni C(85, 130, 170 and 215 mg/kg of weight) were administered for 6 days, after treatment with the carbon tetrachloride. glutamic piruvic and glutamic oxaloacetic transaminase levels were determined, as well as hepatic lesions such as cell tumors, reactive hepatitis, steatosis and necrosis. Results: glutamic piruvic and glutamic oxaloacetic transaminases levels significantly decreased at doses of 85 and 170 mg/kg of Noni C, and no necrosis or steatosis was observed in the groups treated with 170 and 215 mg/kg doses. Conclusions: the carbon tetrachloride-induced hepatic damage diminished in the groups treated with Noni C

Relationship between serum transforming growth factor ß1 and liver collagen content in rats treated with carbon tetrachloride / Relação entre fator transformador de crescimento β1 e conteúdo hepático de colágeno em ratos tratados com tetracloreto de carbono

CONTEXT: Transforming Growth Factor ß1 (TGFß1) plays a fundamental role in fibrogenesis, although its importance as a biomarker of liver disease is still matter of debate. OBJECTIVE: Quantify serum TGFß1 and its association to liver collagen content in rats exposed to Carbon Tetrachloride (CCl4). METHODS: Rats were submitted to a fibrosis model using CCl4 and sacrificed after 6, 10, 12 and 16 weeks of treatment. Serum levels of TGFß1 were measured by ELISA and collagen content was defined by morphometric analysis. RESULTS: Serum levels of TGFß1 increased between 6 and 10 weeks, whereas collagen density increased between 12 and 16 weeks. A negative correlation was observed between liver collagen deposition and serum levels of TGFß1 (r = -0. 48; P<0. 05). CONCLUSION: Serum levels of TGFß1 were inversely proportional to collagen intensity in cirrhotic livers of rats exposed to CCl4, thus suggesting a limited use as biomarker in advanced liver disease.

CONTEXTO: A citocina TGFß1 (Fator Transformador de Crescimento, TGFß1) desempenha um papel fundamental na fibrogênese, mas sua importância como biomarcador da doença hepática ainda tem sido debatida. OBJETIVO: Quantificar o TGFß1 sérico e estudar a sua associação com o conteúdo de colágeno no tecido hepático em ratos expostos ao Tetracloreto de Carbono (CCl4). MÉTODOS: Ratos foram submetidos ao modelo de fibrose por CCl4 e sacrificados após 6, 10, 12 e 16 semanas de tratamento. Os níveis séricos de TGFß1 foram quantificados por ELISA e a densidade de colágeno foi definida por morfometria. RESULTADOS: Os níveis séricos de TGFß1 aumentaram entre 6 e 10 semanas, enquanto a densidade de colágeno aumentou entre 12 e 16 semanas. Foi detectada uma correlação negativa entre a deposição hepática de colágeno e a concentração sérica de TGFß1 (r = -0,48; P<0,05). CONCLUSÃO: O nível sérico de TGFß1 foi inversamente proporcional à intensidade do colágeno no fígado de ratos com cirrose por CCl4, o que indica que seu uso como biomarcador em estágios avançados da doença pode ter utilidade limitada.

Review of experimental models for inducing hepatic cirrhosis by bile duct ligation and carbon tetrachloride injection / Revisão de modelos experimentais de cirrose hepática induzida por ligadura do ducto biliar e por injeção de tetracloreto de carbono

PURPOSE: To present a review about a comparative study of bile duct ligation versus carbon tetrachloride Injection for inducing experimental liver cirrhosis. METHODS: This research was made through Medline/PubMed and SciELO web sites looking for papers on the content "induction of liver cirrhosis in rats". We have found 107 articles but only 30 were selected from 2004 to 2011. RESULTS: The most common methods used for inducing liver cirrhosis in the rat were administration of carbon tetrachloride (CCl4) and bile duct ligation (BDL). CCl4 has induced cirrhosis from 36 hours to 18 weeks after injection and BDL from seven days to four weeks after surgery. CONCLUSION: For a safer inducing cirrhosis method BDL is better than CCl4 because of the absence of toxicity for researches and shorter time for achieving it.

OBJETIVO: Apresentar revisão sobre estudo comparativo da indução de cirrose hepática (CH) experimental com a injeção de tetra-cloreto de carbono (CCl4) comparado à ligadura do ducto biliar (BDL). MÉTODOS: A pesquisa foi realizada nas bases de dados do Medline/PubMed e SciELO procurando trabalhos com as palavras indução de CH e ratos. Foram encontrados 107 artigos, mas somente 30 foram selecionados no período de 2004 à 2011. RESULTADOS: Os procedimentos mais comum para indução de CH em ratos foram a injeção de CCl4 e a BDL. O CCl4 induzia CH no período de 36 horas após a injeção e a DBL de sete dias à quatro semanas após a cirurgia. CONCLUSÃO: A BDL é o método mais seguro para indução de CH quando comparado a injeção de CCl4 pela ausência de toxicidade para os pesquisadores e o menor tempo para se obter a lesão hepática.