Avaliação ultrassonográfica das vias biliares em cães e gatos: coletas e análises de registros médicos veterinários / Ultrasonographic evaluation of the bile ducts in dogs and cats: Collections and analyses of veterinary medical records

Este estudo teve como objetivo avaliar achados ultrassonográficos de cães e gatos diagnosticados com colestase, correlacionando alterações concomitantes com espécies, sexo, idade, peso, sinais clínicos e dilatação das vias biliares. O sistema biliar de pequenos animais é composto pela vesícula biliar e a árvore biliar. Desta forma, os felinos apresentam mais alterações nestas estruturas devido à anatomia diferenciada. A redução do fluxo biliar, conhecida como colestase, ocorre por inúmeras situações, sendo o ultrassom o principal exame diagnóstico empregado na medicina veterinária. Ductos biliares de 4 e 3mm de diâmetro são considerados normais para felinos e caninos, respectivamente. Neste estudo, os sistemas biliares de 41 animais, incluindo felinos e caninos, foram avaliados por ultrassonografia no Setor de Diagnóstico por Imagem do Hospital Veterinário de janeiro de 2019 a fevereiro de 2020, demonstrando a presença de cálculos vesicais em ambas as populações, assim como alterações em ducto cístico associados à pancreatite em cães.

This study aimed to evaluate ultrasound findings of dogs and cats diagnosed with cholestasis, correlating concomitant alterations with species, sex, age, weight, clinical signs, and dilation of bile ducts. The biliary system of small animals is composed of the gallbladder and the biliary tree. Thus, the felines show more alterations in these structures due to their differentiated anatomy. The reduction of the bile flow, known as cholestasis, occurs as a result of numerous situations, with ultrasound being the main diagnostic exam applied in veterinary medicine. Bile ducts of 4 and 3mm diameter are considered normal for felines and canines, respectively. In this study, the biliary systems of 41 animals, including felines and canines, were evaluated using ultrasound at the Diagnostic Imaging Sector of the Veterinary Hospital from January 2019 to February 2020, demonstrating the presence of bladder stones in both populations, as well as changes in the cystic duct associated with pancreatitis in dogs.

Atypical chronic copper poisoning in a sheep secondary to copper wire ingestion: case report / Intoxicação crônica por cobre atípica em ovino pelo consumo de fios de cobre: relato de caso

A 14-month-old female Texel sheep that came from a herd made up of 19 animals showed haemoglobinuria, apathy, and anorexia, and died two days after the start of the clinical signals. The sheep remained in a natural grassland, where trailers were repaired, and multiple copper wires were deposited on the pasture. The animal had tachycardia, tachypnoea, pale mucous membranes, groaning pain on abdominal palpation, circling, head pressing, intensely hemolyzed plasma, and intense azotaemia. The necropsy showed focally extensive oedema in the inguinal and medial region of pelvic limbs, kidneys dark brown, and liver diffusely yellow with an evident moderate diffuse lobular pattern. The abomasum had a considerable amount of enameled material of thickness, firm to the cut, with 1-5 mm (copper wires). Histopathological examination showed marked diffuse tubular and glomerular coagulative necrosis in the kidneys, in addition to neutrophils, macrophages, lymphocytes, and plasma cells with moderate multifocal nephritis. The liver showed centrilobular necrosis, moderate hepatocellular edema, multifocal cholestasis, and in the lungs and brain mild to moderate diffuse edema. Copper content in the frozen liver (in natura) reached 1,598 mg/kg. Copper mesh ingestion led to sheep poisoning, which in this case was considered an atypical form of chronic primary copper poisoning.

Um ovino Texel de 14 meses de idade, que fazia parte de um rebanho de 19 animais, apresentou hemoglobinúria, apatia, anorexia e morreu dois dias após o início dos sinais clínicos. Os ovinos permaneciam em campo nativo, onde eram realizados consertos de trailers, e múltiplos fios de cobre ficavam depositados na pastagem. O animal apresentou taquicardia, taquipneia, mucosas pálidas, gemido de dor à palpação abdominal, além de andar em círculo, e pressão da cabeça contra obstáculos, plasma intensamente hemolisado e azotemia intensa. Na necropsia, havia edema na região inguinal e medial de membros pélvicos focalmente extenso, rins enegrecidos, e o fígado estava difusamente amarelado, com padrão lobular evidente difuso moderado. No abomaso, havia grande quantidade de material esmaltado, com 1-5mm de espessura, firme, que rangia ao ser cortado (fios de cobre). No exame histopatológico nos rins, havia necrose tubular e glomerular hemoglobinúrica difusa acentuada, além de nefrite de neutrófilios, macrófagos, linfócitos e plasmócitos multifocal moderada. No fígado, havia necrose centrolobular, tumefação hepatocelular e colestase multifocais moderadas; nos pulmões e no cérebro, edema difuso discreto a moderado. A dosagem de Cu no fígado revelou a presença de 1598mg/kg. A ingestão de malhas de cobre levou à intoxicação do ovino que, nesse caso, foi considerada uma forma atípica de intoxicação primária crônica por cobre.

Acute necrotic hepatotoxicity caused by Lantana camara L. ingestion in dairy cattle

ABSTRACT: This study describes an outbreak of acute necrotic hepatopathy associated with spontaneous poisoning by Lantana camara L. in dairy cattle. A herd of 15 cows and heifers was introduced into a native pasture with limited food supply, and, sixteen days later, eight animals had spontaneous nasal hemorrhage, fever, lethargy, jaundice, and dry, dark stools with mucus and blood. The clinical course varied from two to five days. In the pasture where the cattle were kept, abundant adult specimens of L. camara L. with evident signs of consumption were observed. In total, seven cattle died and necropsy was performed in three of them. All animals had moderate jaundice, hemorrhage in the subcutaneous tissue and on the surface of different organs. The liver was slightly enlarged, with orange discoloration and enhanced lobular pattern. Histologically, multifocal areas of coagulative necrosis of hepatocytes in the centrilobular area, occasionally extending to the midzonal area, were observed, as well as marked hepatocellular degeneration and prominent cholestasis. The current study suggests that L. camara L. poisoning should be considered a differential diagnosis of acute and necrotic hepatotoxicity in cattle, despite the absence of photosensitization.

RESUMO: Esse estudo descreve um surto de hepatopatia necrótica aguda associada a intoxicação espontânea por Lantana camara L. em bovinos leiteiros. Um lote de 15 vacas e novilhas foram introduzidas em um piquete com campo nativo, com escassa oferta de alimento. Após dezesseis dias, oito animais manifestaram epistaxe, febre, apatia, icterícia, fezes ressecadas e escuras com muco e sangue. A evolução do quadro clínico variou de dois a cinco dias. No piquete em que os bovinos estavam alojados havia grande quantidade de L. camara L. com sinais evidentes de consumo. No total, sete bovinos morreram, e destes, o exame post mortem foi realizado em três. Os bovinos exibiam moderada icterícia, hemorragias no tecido subcutâneo e na superfície de diferentes órgãos. O fígado estava discretamente aumentado, com coloração alaranjada e padrão lobular evidente. As lesões histológicas consistiam em acentuada necrose de coagulação de hepatócitos em região centrolobular, por vezes se estendendo a região mediozonal, além de acentuada degeneração dos hepatócitos e evidente Colestase. O presente trabalho alerta para que intoxicação por L. camara L. seja levada em consideração nos diagnósticos diferenciais de hepatotoxicidade necrótica aguda em bovinos, mesmo sem indícios de fotossensibilização.

Hepatic encephalopathy in adult dog secondary to cirrhosis due to congenital biliary agenesis: a case report / Encefalopatia hepática em cão adulto secundária a cirrose causada por agenesia biliar congênita: relato de caso

Gallbladder agenesis is a congenital malformation that is considered extremely rare in dogs. The disease can course asymptomatically or with clinical signs, usually non-specific and including vomiting, anorexia, diarrhea, ascites, and lethargy. The objective of this report was to describe the clinical and anatomopathological aspects of a dog with hepatic encephalopathy secondary to gallbladder agenesis. This condition can be diagnosed during surgery or imaging examinations; however, it is often an incidental finding. In the biochemical examinations, a decrease in alanine aminotransferase and an increase in alkaline phosphatase and hypoalbuminemia were observed. During the necropsy, hepatomegaly was observed with absence of the gallbladder, congestion, cerebral edema, lipiduria, and pulmonary edema. Microscopically, there was intense fibrosis and inflammation in the liver due to chronic cholangiohepatitis (cirrhosis of the liver). The consequence of this lesion secondary to gallbladder agenesis was hepatic encephalopathy. Chronic liver failure exposes the cerebral cortex to toxins that are not metabolized by the liver, such as ammonia, mercaptans, short-chain fatty acids, scatols, indols, and aromatic amino acids. These toxins cause reversible damage to the brain, which results in neurological disorders. In this report, the dog had no clinical neurological signs, and the diagnosis of this condition was observed histologically. Dogs with gallbladder agenesis usually have clinical and pathological findings of hepatobiliary lesions such as cholestasis, cholangiohepatitis, and, in severe cases, hepatic encephalopathy, which are necessary to differentiate from other diseases that affect the hepatobiliary system, such as cholelithiasis, neoplasms, and chronic hepatitis.

A agenesia de vesícula biliar é uma má formação congênita, considerada extremamente rara em cães. A doença pode cursar de forma assintomática ou com sinais clínicos, geralmente, inespecíficos que incluem vômitos, anorexia, diarreia, ascite e letargia. O objetivo deste relato foi descrever os aspectos clínicos e anatomopatológicos de um cão com encefalopatia hepá-tica secundária a agenesia da vesícula biliar, esta condição pode ser diagnosticada durante uma cirurgia ou exames de imagem, entretanto frequentemente é um achado incidental. Como resultados, nos exames bioquímicos observou-se a diminuição da alanina aminotransferase, aumento da fosfatase alcalina e hipoalbuminemia. Durante a necropsia foi observado hepatomegalia com ausência da vesícula biliar, congestão e edema cerebral, lipidúria e edema pulmonar. Microscopicamente, no fígado havia intensa fibrose e inflamação pela colangiohepatite crônica (cirrose hepática). A consequência desta lesão secundária a agenesia da vesícula biliar, foi a encefalopatia hepática. A insuficiência hepática crônica expõe o córtex cerebral às toxinas não metabo-lizadas pelo fígado, tais como a amônia, mercaptanos, ácidos graxos de cadeia curta, escatóis, indóis e aminoácidos aromáti-cos. Essas toxinas causam danos reversíveis ao encéfalo, o que resulta em distúrbios neurológicos. No presente caso, o cão não apresentou sinais clínicos neurológicos e o diagnóstico desta condição foi observado histologicamente. Cães com agenesia de vesícula biliar, geralmente exibem achados clínicos e patológicos de lesões hepatobiliares, como colestase, conlangiohepatite e, em casos graves, encefalopatia hepática, sendo necessário diferenciar de outras doenças que acometem o sistema hepatobiliar, como colelitíase, neoplasias e hepatites crônicas.

Hepatic encephalopathy in adult dog secondary to cirrhosis due to congenital biliary agenesis: a case report / Encefalopatia hepática em cão adulto secundária a cirrose causada por agenesia biliar congênita: relato de caso

Gallbladder agenesis is a congenital malformation that is considered extremely rare in dogs. The disease can course asymptomatically or with clinical signs, usually non-specific and including vomiting, anorexia, diarrhea, ascites, and lethargy. The objective of this report was to describe the clinical and anatomopathological aspects of a dog with hepatic encephalopathy secondary to gallbladder agenesis. This condition can be diagnosed during surgery or imaging examinations; however, it is often an incidental finding. In the biochemical examinations, a decrease in alanine aminotransferase and an increase in alkaline phosphatase and hypoalbuminemia were observed. During the necropsy, hepatomegaly was observed with absence of the gallbladder, congestion, cerebral edema, lipiduria, and pulmonary edema. Microscopically, there was intense fibrosis and inflammation in the liver due to chronic cholangiohepatitis (cirrhosis of the liver). The consequence of this lesion secondary to gallbladder agenesis was hepatic encephalopathy. Chronic liver failure exposes the cerebral cortex to toxins that are not metabolized by the liver, such as ammonia, mercaptans, short-chain fatty acids, scatols, indols, and aromatic amino acids. These toxins cause reversible damage to the brain, which results in neurological disorders. In this report, the dog had no clinical neurological signs, and the diagnosis of this condition was observed histologically. Dogs with gallbladder agenesis usually have clinical and pathological findings of hepatobiliary lesions such as cholestasis, cholangiohepatitis, and, in severe cases, hepatic encephalopathy, which are necessary to differentiate from other diseases that affect the hepatobiliary system, such as cholelithiasis, neoplasms, and chronic hepatitis.(AU)

A agenesia de vesícula biliar é uma má formação congênita, considerada extremamente rara em cães. A doença pode cursar de forma assintomática ou com sinais clínicos, geralmente, inespecíficos que incluem vômitos, anorexia, diarreia, ascite e letargia. O objetivo deste relato foi descrever os aspectos clínicos e anatomopatológicos de um cão com encefalopatia hepá-tica secundária a agenesia da vesícula biliar, esta condição pode ser diagnosticada durante uma cirurgia ou exames de imagem, entretanto frequentemente é um achado incidental. Como resultados, nos exames bioquímicos observou-se a diminuição da alanina aminotransferase, aumento da fosfatase alcalina e hipoalbuminemia. Durante a necropsia foi observado hepatomegalia com ausência da vesícula biliar, congestão e edema cerebral, lipidúria e edema pulmonar. Microscopicamente, no fígado havia intensa fibrose e inflamação pela colangiohepatite crônica (cirrose hepática). A consequência desta lesão secundária a agenesia da vesícula biliar, foi a encefalopatia hepática. A insuficiência hepática crônica expõe o córtex cerebral às toxinas não metabo-lizadas pelo fígado, tais como a amônia, mercaptanos, ácidos graxos de cadeia curta, escatóis, indóis e aminoácidos aromáti-cos. Essas toxinas causam danos reversíveis ao encéfalo, o que resulta em distúrbios neurológicos. No presente caso, o cão não apresentou sinais clínicos neurológicos e o diagnóstico desta condição foi observado histologicamente. Cães com agenesia de vesícula biliar, geralmente exibem achados clínicos e patológicos de lesões hepatobiliares, como colestase, conlangiohepatite e, em casos graves, encefalopatia hepática, sendo necessário diferenciar de outras doenças que acometem o sistema hepatobiliar, como colelitíase, neoplasias e hepatites crônicas.(AU)

Acute necrotic hepatotoxicity caused by Lantana camara L. ingestion in dairy cattle / Hepatotoxicidade necrótica aguda por ingestão de Lantana camara L. em bovinos leiteiros

This study describes an outbreak of acute necrotic hepatopathy associated with spontaneous poisoning by Lantana camara L. in dairy cattle. A herd of 15 cows and heifers was introduced into a native pasture with limited food supply, and, sixteen days later, eight animals had spontaneous nasal hemorrhage, fever, lethargy, jaundice, and dry, dark stools with mucus and blood. The clinical course varied from two to five days. In the pasture where the cattle were kept, abundant adult specimens of L. camara L. with evident signs of consumption were observed. In total, seven cattle died and necropsy was performed in three of them. All animals had moderate jaundice, hemorrhage in the subcutaneous tissue and on the surface of different organs. The liver was slightly enlarged, with orange discoloration and enhanced lobular pattern. Histologically, multifocal areas of coagulative necrosis of hepatocytes in the centrilobular area, occasionally extending to the midzonal area, were observed, as well as marked hepatocellular degeneration and prominent cholestasis. The current study suggests that L. camara L. poisoning should be considered a differential diagnosis of acute and necrotic hepatotoxicity in cattle, despite the absence of photosensitization.(AU)

Esse estudo descreve um surto de hepatopatia necrótica aguda associada a intoxicação espontânea por Lantana camara L. em bovinos leiteiros. Um lote de 15 vacas e novilhas foram introduzidas em um piquete com campo nativo, com escassa oferta de alimento. Após dezesseis dias, oito animais manifestaram epistaxe, febre, apatia, icterícia, fezes ressecadas e escuras com muco e sangue. A evolução do quadro clínico variou de dois a cinco dias. No piquete em que os bovinos estavam alojados havia grande quantidade de L. camara L. com sinais evidentes de consumo. No total, sete bovinos morreram, e destes, o exame post mortem foi realizado em três. Os bovinos exibiam moderada icterícia, hemorragias no tecido subcutâneo e na superfície de diferentes órgãos. O fígado estava discretamente aumentado, com coloração alaranjada e padrão lobular evidente. As lesões histológicas consistiam em acentuada necrose de coagulação de hepatócitos em região centrolobular, por vezes se estendendo a região mediozonal, além de acentuada degeneração dos hepatócitos e evidente Colestase. O presente trabalho alerta para que intoxicação por L. camara L. seja levada em consideração nos diagnósticos diferenciais de hepatotoxicidade necrótica aguda em bovinos, mesmo sem indícios de fotossensibilização.(AU)

Acute necrotic hepatotoxicity caused by Lantana camara L. ingestion in dairy cattle / Hepatotoxicidade necrótica aguda por ingestão de Lantana camara L. em bovinos leiteiros

This study describes an outbreak of acute necrotic hepatopathy associated with spontaneous poisoning by Lantana camara L. in dairy cattle. A herd of 15 cows and heifers was introduced into a native pasture with limited food supply, and, sixteen days later, eight animals had spontaneous nasal hemorrhage, fever, lethargy, jaundice, and dry, dark stools with mucus and blood. The clinical course varied from two to five days. In the pasture where the cattle were kept, abundant adult specimens of L. camara L. with evident signs of consumption were observed. In total, seven cattle died and necropsy was performed in three of them. All animals had moderate jaundice, hemorrhage in the subcutaneous tissue and on the surface of different organs. The liver was slightly enlarged, with orange discoloration and enhanced lobular pattern. Histologically, multifocal areas of coagulative necrosis of hepatocytes in the centrilobular area, occasionally extending to the midzonal area, were observed, as well as marked hepatocellular degeneration and prominent cholestasis. The current study suggests that L. camara L. poisoning should be considered a differential diagnosis of acute and necrotic hepatotoxicity in cattle, despite the absence of photosensitization.(AU)

Esse estudo descreve um surto de hepatopatia necrótica aguda associada a intoxicação espontânea por Lantana camara L. em bovinos leiteiros. Um lote de 15 vacas e novilhas foram introduzidas em um piquete com campo nativo, com escassa oferta de alimento. Após dezesseis dias, oito animais manifestaram epistaxe, febre, apatia, icterícia, fezes ressecadas e escuras com muco e sangue. A evolução do quadro clínico variou de dois a cinco dias. No piquete em que os bovinos estavam alojados havia grande quantidade de L. camara L. com sinais evidentes de consumo. No total, sete bovinos morreram, e destes, o exame post mortem foi realizado em três. Os bovinos exibiam moderada icterícia, hemorragias no tecido subcutâneo e na superfície de diferentes órgãos. O fígado estava discretamente aumentado, com coloração alaranjada e padrão lobular evidente. As lesões histológicas consistiam em acentuada necrose de coagulação de hepatócitos em região centrolobular, por vezes se estendendo a região mediozonal, além de acentuada degeneração dos hepatócitos e evidente Colestase. O presente trabalho alerta para que intoxicação por L. camara L. seja levada em consideração nos diagnósticos diferenciais de hepatotoxicidade necrótica aguda em bovinos, mesmo sem indícios de fotossensibilização.(AU)

Colecistoduodenostomia para tratamento de obstrução biliar secundária a platinossomose felina / Cholecystoduodenostomy for treatment of biliary obstruction secondary to feline platinossomosis

Background: Platynosomum spp. it is a trematode that has a predilection for the liver and biliary tissues whose infection isacquired through the ingestion of metacercarian gecko viscera. Felines are the definitive hosts and clinical signs are variable.The diagnosis is through history, hematological and biochemical exams, ultrasound, bile cytology or histopathology. Thetreatment of choice is cholecystoduodenostomy. This paper aims to report the case of a cat who was treated at the UberabaVeterinary Hospital with chronic cholangitis secondary to platinosomosis, but there was a transfusion reaction and she died.Case: A 4-year-old, uncastrated SRD cat was treated at the Uberaba Veterinary Hospital complaining of severe episodesof vomiting three days ago, hyporexia and darkened urine. The general clinical examination showed moderate dehydration, jaundice and hepatomegaly. The animal was hospitalized for better investigation of its condition. Increased valuesof ALT, alkaline phosphatase and all bilirubins were observed. Ultrasound showed liver suggestive of liver disease andsteatosis, and gallbladder without alteration. During hospitalization, she remained jaundiced and hypoxic, and the esophageal tube was placed. The initial clinical suspicion was cholangiohepatitis. Liver biopsy and cholecystoduodenostomywere then suggested, with refusal by the tutor. The ultrasound was repeated and showed the same alterations described,besides cholangitis. Stool examination was negative for Platynosomum spp. and positive for Isospora spp. The patientwas treated with anthelmintic for three days and received supportive treatment for another week until the tutor authorizedcholecystoduodenostomy. During surgery, cholecystocentesis was performed and the parasite Platynosomum spp. in adultform. After four days, a new blood count was done and the animal was still anemic and the blood...

Colecistoduodenostomia para tratamento de obstrução biliar secundária a platinossomose felina / Cholecystoduodenostomy for treatment of biliary obstruction secondary to feline platinossomosis

Background: Platynosomum spp. it is a trematode that has a predilection for the liver and biliary tissues whose infection isacquired through the ingestion of metacercarian gecko viscera. Felines are the definitive hosts and clinical signs are variable.The diagnosis is through history, hematological and biochemical exams, ultrasound, bile cytology or histopathology. Thetreatment of choice is cholecystoduodenostomy. This paper aims to report the case of a cat who was treated at the UberabaVeterinary Hospital with chronic cholangitis secondary to platinosomosis, but there was a transfusion reaction and she died.Case: A 4-year-old, uncastrated SRD cat was treated at the Uberaba Veterinary Hospital complaining of severe episodesof vomiting three days ago, hyporexia and darkened urine. The general clinical examination showed moderate dehydration, jaundice and hepatomegaly. The animal was hospitalized for better investigation of its condition. Increased valuesof ALT, alkaline phosphatase and all bilirubins were observed. Ultrasound showed liver suggestive of liver disease andsteatosis, and gallbladder without alteration. During hospitalization, she remained jaundiced and hypoxic, and the esophageal tube was placed. The initial clinical suspicion was cholangiohepatitis. Liver biopsy and cholecystoduodenostomywere then suggested, with refusal by the tutor. The ultrasound was repeated and showed the same alterations described,besides cholangitis. Stool examination was negative for Platynosomum spp. and positive for Isospora spp. The patientwas treated with anthelmintic for three days and received supportive treatment for another week until the tutor authorizedcholecystoduodenostomy. During surgery, cholecystocentesis was performed and the parasite Platynosomum spp. in adultform. After four days, a new blood count was done and the animal was still anemic and the blood...(AU)

Protective effect of Echinochrome against intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats / Efeito protetor de Echinochrome contra colestase intra-hepática induzida por isotiocianato de alfa-naftilo em ratos

The present study was designed to evaluate the protective effects of echinochrome (Ech) on intrahepatic cholestasis in rats induced by a single (i.p.) injection of alpha-naphthylisothiocyanate (ANIT) (75 mg/kg body weight). The rats were pre-treated orally for 48hr (one dose / 24hr) with Ech (1, 5 and 10 mg/kg body weight) or ursodeoxycholic acid (UDCA) 80 mg/kg body weight drug then, injected with ANIT. ANIT markedly increased serum activities of alanine amino transaminase (ALT), aspartate amino transaminase (AST) and alkaline phosphatase (ALP), which was accompanied by a massive inflammation of epithelial cells on bile duct at 24h after ANIT injection. ANIT also increased the levels of total protein (TP), total bilirubin (TB), direct bilirubin (DB), indirect bilirubin (IB), however decrease albumin content (ALB). In addition ANIT increased hepatic MDA and NO level and decreased GSH level and GST activity. The Ech exerted hepatoprotective and anticholestatic effects as assessed by a significant decrease in the activities of serum AST, ALT and ALP, and the levels of TP, TB, DB and IB as well as liver MDA level and NO level. In conclusion, Ech was found to possess hepatoprotective effect against intrahepatic cholestasis induced by hepatotoxin such as ANIT.(AU)

O presente estudo destinou-se a avaliar os efeitos protetores do Ech na colestase intra-hepática em ratos induzidos por uma única injeção (i.p.) de alfa-naftilisotiocianato (ANIT) (75 mg / kg de peso corporal). Os ratos foram pré-tratados oralmente durante 48 horas (uma dose / 24 horas) com cada (1, 5 e 10 mg / kg de peso corporal) e ácido ursodeoxicólico (UDCA) 80 mg / kg de peso corporal, em seguida, injetado com ANIT. ANIT atividades de soro marcadamente aumentadas de alanina amino transaminasa (ALT), aspartato de amino transaminases (AST) e fosfatase alcalina (ALP), que foi acompanhada por uma inflamação maciça de células epiteliais no ducto biliar às 24h após a injeção de ANIT. A ANIT também aumentou os níveis de proteína total (TP), bilirrubina total (TB), bilirrubina direta (DB), bilirrubina indireta (IB), no entanto, diminuem o teor de albumina (ALB). Além disso, a ANIT aumentou o nível de MDA hepático e NO e diminuiu o nível de GSH e a atividade de GST. O Ech exerceu efeitos hepatoprotectores e anticolestáticos como avaliado por uma diminuição significativa nas atividades de AST sérica, ALT e ALP e os níveis de TP, TB, DB e IB, bem como o nível de MDA no fígado e o nível de NO. Ech foi encontrado para possuir efeito protetor no fígado contra a colestase intra-hepática induzida por hepatotoxina, como a ANIT.(AU)

Chronic copper poisoning in beef cattle in the state of Mato Grosso, Brazil / Intoxicação crônica por cobre em bovinos de corte no Estado de Mato Grosso, Brasil

Copper is an essential micromineral in animal feed; however, when consumed in excess, it can cause liver necrosis, hemolytic crisis, hemoglobinuric nephrosis and death in cattle. Although uncommon in this species, copper poisoning occurs as a result of exacerbated supplementation, deficiency of antagonist microminerals, or previous liver lesions. An outbreak of chronic copper poisoning is reported in semi-confined cattle after supplementation with 50 mg/Kg of dry matter copper. The cattle showed clinical signs characterized by anorexia, motor incoordination, loss of balance, jaundice, brownish or black urine, diarrhea and death, or were found dead, 10 to 302 days after consumption. Of the 35 cattle that died, 20 underwent necropsy, whose frequent findings were jaundice, enlarged liver with evident lobular pattern, black kidneys, and urinary bladder with brownish to blackish content. Microscopically, the liver showed vacuolar degeneration and/or zonal hepatocellular centrilobular or paracentral coagulative necrosis, in addition to cholestasis, mild periacinal fibrosis, apoptotic bodies, and mild to moderate mononuclear inflammation. Degeneration and necrosis of the tubular epithelium and intratubular hemoglobin cylinders were observed in the kidneys. Copper levels in the liver and kidneys ranged from 5,901.24 to 28,373.14 µmol/kg and from 303.72 to 14,021 µmol/kg, respectively. In conclusion, copper poisoning due to excessive nutritional supplementation is an important cause of jaundice, hemoglobinuria, and death in semi-confined cattle.(AU)

Cobre é um micromineral essencial, que quando em excesso induz necrose hepática, crise hemolítica, nefrose hemoglobínurica e morte em bovinos. As intoxicações, apesar de incomuns nessa espécie, ocorrem devido a suplementação exacerbada de cobre, pela deficiência de microminerais antagonistas ou secundária a lesão hepática prévia. Relata-se um surto de intoxicação crônica por cobre em bovinos semiconfinados após suplementação com 50mg/kg de cobre em matéria seca. Os bovinos manifestaram sinais clínicos caracterizados por anorexia, incoordenação motora, perda de equilíbrio, icterícia, urina acastanhada ou negra, diarreia e morte ou foram encontrados mortos, após 10 a 302 dias do início de consumo. De 35 bovinos que morreram 20 foram submetidos à necropsia sendo achada frequente icterícia, fígado aumentado e com padrão lobular evidente, rins pretos e bexiga urinária repleta de conteúdo acastanhado a enegrecida. Microscopicamente, no fígado havia degeneração vacuolar e ou necrose coagulativa hepatocelular zonal, centrolobular ou paracentral, além de degeneração vacuolar com corpúsculos de Councilman, colestase, fibrose periascinar leve, e inflamação de discreta a moderada. Nos rins havia degeneração e necrose do epitélio tubular assim como cilindros de hemoglobina intratubulares. Os níveis de cobre no fígado e rim foram de 5.901,24 a 28.373,14µmol/kg e 303,72 a 14.021µmol/kg respectivamente. A suplementação nutricional excessiva com cobre pode causar doença hemolítica com icterícia, hemoglobinúria e morte de bovinos mantidos em sistema de semiconfinamento.(AU)

Chronic copper poisoning in beef cattle in the state of Mato Grosso, Brazil / Intoxicação crônica por cobre em bovinos de corte no Estado de Mato Grosso, Brasil

Copper is an essential micromineral in animal feed; however, when consumed in excess, it can cause liver necrosis, hemolytic crisis, hemoglobinuric nephrosis and death in cattle. Although uncommon in this species, copper poisoning occurs as a result of exacerbated supplementation, deficiency of antagonist microminerals, or previous liver lesions. An outbreak of chronic copper poisoning is reported in semi-confined cattle after supplementation with 50 mg/Kg of dry matter copper. The cattle showed clinical signs characterized by anorexia, motor incoordination, loss of balance, jaundice, brownish or black urine, diarrhea and death, or were found dead, 10 to 302 days after consumption. Of the 35 cattle that died, 20 underwent necropsy, whose frequent findings were jaundice, enlarged liver with evident lobular pattern, black kidneys, and urinary bladder with brownish to blackish content. Microscopically, the liver showed vacuolar degeneration and/or zonal hepatocellular centrilobular or paracentral coagulative necrosis, in addition to cholestasis, mild periacinal fibrosis, apoptotic bodies, and mild to moderate mononuclear inflammation. Degeneration and necrosis of the tubular epithelium and intratubular hemoglobin cylinders were observed in the kidneys. Copper levels in the liver and kidneys ranged from 5,901.24 to 28,373.14 µmol/kg and from 303.72 to 14,021 µmol/kg, respectively. In conclusion, copper poisoning due to excessive nutritional supplementation is an important cause of jaundice, hemoglobinuria, and death in semi-confined cattle.(AU)

Cobre é um micromineral essencial, que quando em excesso induz necrose hepática, crise hemolítica, nefrose hemoglobínurica e morte em bovinos. As intoxicações, apesar de incomuns nessa espécie, ocorrem devido a suplementação exacerbada de cobre, pela deficiência de microminerais antagonistas ou secundária a lesão hepática prévia. Relata-se um surto de intoxicação crônica por cobre em bovinos semiconfinados após suplementação com 50mg/kg de cobre em matéria seca. Os bovinos manifestaram sinais clínicos caracterizados por anorexia, incoordenação motora, perda de equilíbrio, icterícia, urina acastanhada ou negra, diarreia e morte ou foram encontrados mortos, após 10 a 302 dias do início de consumo. De 35 bovinos que morreram 20 foram submetidos à necropsia sendo achada frequente icterícia, fígado aumentado e com padrão lobular evidente, rins pretos e bexiga urinária repleta de conteúdo acastanhado a enegrecida. Microscopicamente, no fígado havia degeneração vacuolar e ou necrose coagulativa hepatocelular zonal, centrolobular ou paracentral, além de degeneração vacuolar com corpúsculos de Councilman, colestase, fibrose periascinar leve, e inflamação de discreta a moderada. Nos rins havia degeneração e necrose do epitélio tubular assim como cilindros de hemoglobina intratubulares. Os níveis de cobre no fígado e rim foram de 5.901,24 a 28.373,14µmol/kg e 303,72 a 14.021µmol/kg respectivamente. A suplementação nutricional excessiva com cobre pode causar doença hemolítica com icterícia, hemoglobinúria e morte de bovinos mantidos em sistema de semiconfinamento.(AU)

Protective effect of Echinochrome against intrahepatic cholestasis induced by alpha-naphthylisothiocyanate in rats

Abstract The present study was designed to evaluate the protective effects of echinochrome (Ech) on intrahepatic cholestasis in rats induced by a single (i.p.) injection of alpha-naphthylisothiocyanate (ANIT) (75 mg/kg body weight). The rats were pre-treated orally for 48hr (one dose / 24hr) with Ech (1, 5 and 10 mg/kg body weight) or ursodeoxycholic acid (UDCA) 80 mg/kg body weight drug then, injected with ANIT. ANIT markedly increased serum activities of alanine amino transaminase (ALT), aspartate amino transaminase (AST) and alkaline phosphatase (ALP), which was accompanied by a massive inflammation of epithelial cells on bile duct at 24h after ANIT injection. ANIT also increased the levels of total protein (TP), total bilirubin (TB), direct bilirubin (DB), indirect bilirubin (IB), however decrease albumin content (ALB). In addition ANIT increased hepatic MDA and NO level and decreased GSH level and GST activity. The Ech exerted hepatoprotective and anticholestatic effects as assessed by a significant decrease in the activities of serum AST, ALT and ALP, and the levels of TP, TB, DB and IB as well as liver MDA level and NO level. In conclusion, Ech was found to possess hepatoprotective effect against intrahepatic cholestasis induced by hepatotoxin such as ANIT.

Resumo O presente estudo destinou-se a avaliar os efeitos protetores do Ech na colestase intra-hepática em ratos induzidos por uma única injeção (i.p.) de alfa-naftilisotiocianato (ANIT) (75 mg / kg de peso corporal). Os ratos foram pré-tratados oralmente durante 48 horas (uma dose / 24 horas) com cada (1, 5 e 10 mg / kg de peso corporal) e ácido ursodeoxicólico (UDCA) 80 mg / kg de peso corporal, em seguida, injetado com ANIT. ANIT atividades de soro marcadamente aumentadas de alanina amino transaminasa (ALT), aspartato de amino transaminases (AST) e fosfatase alcalina (ALP), que foi acompanhada por uma inflamação maciça de células epiteliais no ducto biliar às 24h após a injeção de ANIT. A ANIT também aumentou os níveis de proteína total (TP), bilirrubina total (TB), bilirrubina direta (DB), bilirrubina indireta (IB), no entanto, diminuem o teor de albumina (ALB). Além disso, a ANIT aumentou o nível de MDA hepático e NO e diminuiu o nível de GSH e a atividade de GST. O Ech exerceu efeitos hepatoprotectores e anticolestáticos como avaliado por uma diminuição significativa nas atividades de AST sérica, ALT e ALP e os níveis de TP, TB, DB e IB, bem como o nível de MDA no fígado e o nível de NO. Ech foi encontrado para possuir efeito protetor no fígado contra a colestase intra-hepática induzida por hepatotoxina, como a ANIT.

Relations of neuropeptide Y and heme oxygenase-1 expressions with fetal brain injury in rats with intrahepatic cholestasis of pregnancy

Purpose: To investigate the relations of neuropeptide Y (NPY) and heme oxygenase-1 (HO-1) expressions with fetal brain injury in rats with intrahepatic cholestasis of pregnancy (ICP). Methods: Sixty rats pregnant for 15 days were randomly divided into experimental and control groups. The ICP model was established in experimental group. On the 21st day, the blood biochemical test, histopathological examination of pregnant rat liver and fetal brain tissues and immunohistochemical analysis of fetal rat brain tissues were performed. Results: On the 21st day, the alanineaminotransferase, aspartate aminotransferase and total bile acid levels in experimental group were significantly higher than control group (P<0.01). Compared with control group, there was obvious vacuolar degeneration in pregnant rat liver tissue and fetal brain tissue in experimental group. NPY expression in fetal brain tissue was negative in control group and positive in experimental group. HO-1 expression in fetal brain tissue was strongly positive in control group and positive in experimental group. There was significant difference of immunohistochemical staining optical density between two groups (P<0.01). Conclusion: In fetal brain of ICP rats, the NPY expression is increased, and the HO-1 expression is decreased, which may be related to the fetal brain injury.(AU)

Colecistoduodenostomia devido a obstrução total de ducto biliar comum em felino: relato de caso / Colecistoduodenostomia due total obstruction of common biliary duct in feline: case report

As doenças do trato biliar são as patologias hepato-biliares de maior ocorrência em felinos, comumente associadas a processos inflamatórios intestinais e pancreáticos. A obstrução do ducto biliar comum está associada a alta mortalidade e morbidade e pode ocorrer devido doenças inflamatórias, colelitíases, neoplasias, dentre outras causas menos comum. As manifestações clínicas iniciais são inespecíficas, mas a progressão da doença leva a icterícia, emese, anorexia, perda de peso e fezes acólicas. O diagnóstico se dá através de exames laboratoriais e ultrassonografia. A definição de obstrução total do ducto biliar comum requer intervenção cirúrgica, e a definição da técnica irá depender da possível desobstrução do ducto ou restabelecimento do fluxo biliar através da colecistoduodenostomia, ou colecistojejunostomia, associadas a um grande risco cirúrgico e anestésico. Este relato apresenta um caso de um paciente com obstrução total do ducto biliar comum, diagnosticado através da ultrassonografia, sinais clínicos e exames laboratoriais e sua resolução cirúrgica através da técnica de colecistoduodenostomia, que se mostrou efetiva para a melhora clínica do paciente.

Diseases of the biliary tract are the most frequent hepatic biliary diseases in felines, commonly associated with inflammatory bowel and pancreatic processes. Obstruction of the common bile duct is associated with high mortality and morbidity and can occur due to inflammatory diseases, cholelithiasis, neoplasias, among other less common causes. Initial clinical manifestations are nonspecific, but progression of the disease leads to jaundice, emesis, anorexia, weight loss, and stool. The diagnosis is made through laboratory tests and ultrasonography. The definition of total obstruction of the common bile duct requires surgical intervention, and the definition of the technique will depend on the possible duct clearance or reestablishment of the biliary flow through cholecystoduodenostomy, or cholecystochejunostomy, associated with a great surgical and anesthetic risk. This report presents a case of a patient with total obstruction of the common bile duct, diagnosed through ultrasonography, clinical signs and laboratory tests and their surgical resolution through the cholecystoduodenostomy technique, which proved to be effective for the patient’s clinical improvement.

Colecistoduodenostomia devido a obstrução total de ducto biliar comum em felino: relato de caso / Colecistoduodenostomia due total obstruction of common biliary duct in feline: case report

As doenças do trato biliar são as patologias hepato-biliares de maior ocorrência em felinos, comumente associadas a processos inflamatórios intestinais e pancreáticos. A obstrução do ducto biliar comum está associada a alta mortalidade e morbidade e pode ocorrer devido doenças inflamatórias, colelitíases, neoplasias, dentre outras causas menos comum. As manifestações clínicas iniciais são inespecíficas, mas a progressão da doença leva a icterícia, emese, anorexia, perda de peso e fezes acólicas. O diagnóstico se dá através de exames laboratoriais e ultrassonografia. A definição de obstrução total do ducto biliar comum requer intervenção cirúrgica, e a definição da técnica irá depender da possível desobstrução do ducto ou restabelecimento do fluxo biliar através da colecistoduodenostomia, ou colecistojejunostomia, associadas a um grande risco cirúrgico e anestésico. Este relato apresenta um caso de um paciente com obstrução total do ducto biliar comum, diagnosticado através da ultrassonografia, sinais clínicos e exames laboratoriais e sua resolução cirúrgica através da técnica de colecistoduodenostomia, que se mostrou efetiva para a melhora clínica do paciente.(AU)

Diseases of the biliary tract are the most frequent hepatic biliary diseases in felines, commonly associated with inflammatory bowel and pancreatic processes. Obstruction of the common bile duct is associated with high mortality and morbidity and can occur due to inflammatory diseases, cholelithiasis, neoplasias, among other less common causes. Initial clinical manifestations are nonspecific, but progression of the disease leads to jaundice, emesis, anorexia, weight loss, and stool. The diagnosis is made through laboratory tests and ultrasonography. The definition of total obstruction of the common bile duct requires surgical intervention, and the definition of the technique will depend on the possible duct clearance or reestablishment of the biliary flow through cholecystoduodenostomy, or cholecystochejunostomy, associated with a great surgical and anesthetic risk. This report presents a case of a patient with total obstruction of the common bile duct, diagnosed through ultrasonography, clinical signs and laboratory tests and their surgical resolution through the cholecystoduodenostomy technique, which proved to be effective for the patients clinical improvement.(AU)

Colangiografia transcolecística percutânea em cães / Percutaneous transcholecystic cholangiography in dogs

Enfermidades que acometem o sistema biliar dos cães, principalmente as relacionadas a processos obstrutivos, não são raras, sendo em sua maioria, de etiologia grave, necessitando de tratamento cirúrgico. Os métodos de diagnóstico por imagem para investigação de obstruções biliares atualmente realizados na medicina veterinária como a ultrassonografia, radiografia convencional e tomografia computadorizada, apresentam algumas restrições, como sensibilidade insuficiente, e em muitas regiões inviabilidade de realização. Desta forma, vários pacientes são submetidos a procedimentos cirúrgicos antes da obtenção do diagnóstico preciso, que caracterize e identifique o local de obstrução. Neste contexto, o presente trabalho objetivou padronizar e descrever a técnica de colangiografia transcolecística percutânea em cães, consistindo na injeção percutânea de contraste no interior da vesícula biliar por meio de punção ecoguiada, permitindo a visualização e avaliação semiológica das vias biliares intra e extra-hepáticas, mediante projeções radiográficas. A técnica foi executada 10 vezes em seis cães clinicamente saudáveis, sendo a punção da vesícula biliar realizada através do nono espaço intercostal direito próximo ao esterno com auxílio de um cateter 20G, injetando a dose de 1ml de contraste para cada 4kg de peso vivo. Após a injeção do contraste foram efetuadas radiografias seriadas da região abdominal, em projeção lateral esquerda e ventrodorsal, as primeiras projeções foram realizadas imediatamente após a injeção do contraste sendo repetidas após cinco e dez minutos. Nenhum dos animais apresentou quaisquer efeitos colaterais decorrentes da técnica, sendo verificados por meio de observação dos mesmos e provas de função hepática comparativas pré e pós procedimento. A técnica demonstrou eficácia na demonstração radiográfica da árvore biliar, possibilitando a avaliação semiológica das vias biliares intra e extra-hepáticas. Tal avaliação permite identificar, caracterizar e localizar possíveis processos obstrutivos que acometem as vias biliares na espécie canina.(AU)

Obstructive biliary pathway diseases are not rare in dogs, especially those with severe clinical signs and those that need surgical treatment. Image diagnostic exams to evaluate biliary tract, like ultrasound, conventional X-ray and CT, have been used in veterinary medicine with some restrictions such as low sensibility, and in many regions unfeasibility of achievement. Due to this, most of the pacients with biliary obstruction sings are submitted to surgical procedure before an accurate diagnostic of the disease. This paper aimed to standardize and describe the percutaneous transcolecystic cholangiography in dogs that consists in the injection of contrast inside of the gall bladder guided by ultrasound. It allows to see all the bililary tract, using X-ray. The technique was performed 10 times in six clinical healthy dogs. The puncture was performed in the 9th intercostal right space near to the sternum using a 20G catheter, the dose was 1ml per 4kg. After contrast injection, serial radiographs of the abdominal region were made, in left lateral projection and ventrodorsal, the first projections were performed immediately after contrast injection and repeated after five and ten minutes. No animal showed any side effect due to the technique, this was confirmed by observation and by hepatic function evaluation. The technique was considered efficacious to visualize all the biliary tree and to see any possible obstruction in ill dogs.(AU)

Colangiografia transcolecística percutânea em cães / Percutaneous transcholecystic cholangiography in dogs

Enfermidades que acometem o sistema biliar dos cães, principalmente as relacionadas a processos obstrutivos, não são raras, sendo em sua maioria, de etiologia grave, necessitando de tratamento cirúrgico. Os métodos de diagnóstico por imagem para investigação de obstruções biliares atualmente realizados na medicina veterinária como a ultrassonografia, radiografia convencional e tomografia computadorizada, apresentam algumas restrições, como sensibilidade insuficiente, e em muitas regiões inviabilidade de realização. Desta forma, vários pacientes são submetidos a procedimentos cirúrgicos antes da obtenção do diagnóstico preciso, que caracterize e identifique o local de obstrução. Neste contexto, o presente trabalho objetivou padronizar e descrever a técnica de colangiografia transcolecística percutânea em cães, consistindo na injeção percutânea de contraste no interior da vesícula biliar por meio de punção ecoguiada, permitindo a visualização e avaliação semiológica das vias biliares intra e extra-hepáticas, mediante projeções radiográficas. A técnica foi executada 10 vezes em seis cães clinicamente saudáveis, sendo a punção da vesícula biliar realizada através do nono espaço intercostal direito próximo ao esterno com auxílio de um cateter 20G, injetando a dose de 1ml de contraste para cada 4kg de peso vivo. Após a injeção do contraste foram efetuadas radiografias seriadas da região abdominal, em projeção lateral esquerda e ventrodorsal, as primeiras projeções foram realizadas imediatamente após a injeção do contraste sendo repetidas após cinco e dez minutos. Nenhum dos animais apresentou quaisquer efeitos colaterais decorrentes da técnica, sendo verificados por meio de observação dos mesmos e provas de função hepática comparativas pré e pós procedimento... (AU)

Obstructive biliary pathway diseases are not rare in dogs, especially those with severe clinical signs and those that need surgical treatment. Image diagnostic exams to evaluate biliary tract, like ultrasound, conventional X-ray and CT, have been used in veterinary medicine with some restrictions such as low sensibility, and in many regions unfeasibility of achievement. Due to this, most of the pacients with biliary obstruction sings are submitted to surgical procedure before an accurate diagnostic of the disease. This paper aimed to standardize and describe the percutaneous transcolecystic cholangiography in dogs that consists in the injection of contrast inside of the gall bladder guided by ultrasound. It allows to see all the bililary tract, using X-ray. The technique was performed 10 times in six clinical healthy dogs. The puncture was performed in the 9th intercostal right space near to the sternum using a 20G catheter, the dose was 1ml per 4kg. After contrast injection, serial radiographs of the abdominal region were made, in left lateral projection and ventrodorsal, the first projections were performed immediately after contrast injection and repeated after five and ten minutes. No animal showed any side effect due to the technique, this was confirmed by observation and by hepatic function evaluation. The technique was considered efficacious to visualize all the biliary tree and to see any possible obstruction in ill dogs.(AU)

Ameliorative effect of curcumin and vitamin B6 against lithocholic acid-induced cholestasis and liver injury in mice

To examine the therapeutic effect of curcumin and/or vitamin B6 in treatment of cholestasis, a model of cholestasis was induced in mice using lithocholic acid (LCA). Alterations in biochemical parameters and liver histopathological and histochemical changes were examined in cholestatic mice and after treatments with curcumin, vitamin B6 and combination of both. Moreover, hepatic expressions of bilirubin-metabolizing enzymes, their regulatory nuclear receptors, and bile acid lipid transporters were examined using RT-PCR. Cholestatic mice showed an increase in the blood levels of AST, ALT, ALP, direct and total bilirubin and a decrease in cholesterol levels that were ameliorated by treatments. Liver histopathology showed multiple necrotic foci of different sizes spread all over the liver with congestion of hepatic blood vessels in LCA group. These foci were regenerated in hepatic tissues after administration of curcumin and vitamin B6. Immunohistochemical examination of liver showed an increase in glutathione and NF-kB expressions in treated mice. Cholestatic mice showed down-regulation of mRNA expression of hepatic bile acid and bilirubin-metabolizing/detoxifying enzymes (Cyp2b10, Ugt1a1, Sult2a1), their regulatory nuclear receptors (CAR, PXR, farnesoid X receptor), and bile acid/organic anion and lipid transporters (Oatp2, Bsep, Mrp2, Abcg8, Asbt). These changes were ameliorated and restored by treatment with curcumin, vitamin B6 and both. Only of examined genes, NTCP was up-regulated in cholestatic mice. In conclusion, treatment with curcumin mainly, vitamin B6 or the combination of them has the potential to ameliorate changes observed in induced cholestasis.

Ameliorative effect of curcumin and vitamin B6 against lithocholic acid-induced cholestasis and liver injury in mice

To examine the therapeutic effect of curcumin and/or vitamin B6 in treatment of cholestasis, a model of cholestasis was induced in mice using lithocholic acid (LCA). Alterations in biochemical parameters and liver histopathological and histochemical changes were examined in cholestatic mice and after treatments with curcumin, vitamin B6 and combination of both. Moreover, hepatic expressions of bilirubin-metabolizing enzymes, their regulatory nuclear receptors, and bile acid lipid transporters were examined using RT-PCR. Cholestatic mice showed an increase in the blood levels of AST, ALT, ALP, direct and total bilirubin and a decrease in cholesterol levels that were ameliorated by treatments. Liver histopathology showed multiple necrotic foci of different sizes spread all over the liver with congestion of hepatic blood vessels in LCA group. These foci were regenerated in hepatic tissues after administration of curcumin and vitamin B6. Immunohistochemical examination of liver showed an increase in glutathione and NF-kB expressions in treated mice. Cholestatic mice showed down-regulation of mRNA expression of hepatic bile acid and bilirubin-metabolizing/detoxifying enzymes (Cyp2b10, Ugt1a1, Sult2a1), their regulatory nuclear receptors (CAR, PXR, farnesoid X receptor), and bile acid/organic anion and lipid transporters (Oatp2, Bsep, Mrp2, Abcg8, Asbt). These changes were ameliorated and restored by treatment with curcumin, vitamin B6 and both. Only of examined genes, NTCP was up-regulated in cholestatic mice. In conclusion, treatment with curcumin mainly, vitamin B6 or the combination of them has the potential to ameliorate changes observed in induced cholestasis.(AU)