Cytochrome P450 and glutathione in the liver of rats under exclusive sucrose ingestion

1. The objective of the present investigation was to study some of the possible mechanisms involved in the protective effect of sucrose ingestion against liver necrosis induced by acetaminophen. Three groups of male Wistar rats (220-260 g) were submitted to the following experimental conditions for a period of 42 h: free access to a balanced commercial diet (Group I), an exclusive sucrose diet (Group II) and fasting (Group III). At the end of the experiment, hepatic cytochrome P450 levels were measured in 11 rats from each group, plasma antipyrine half-life (t1/2) was determined in 40 rats from each group, and hepatic glutathione (GSH) concentration in 10 rats from each group. GSH consumption elicited by a high dose of acetaminophen (ACP, 1.0 g/kg, by gavage) was also determined in 30 rats each from Groups II and III. 2. The liver of Group II rats presented a significant reduction of cytochrome P450 levels in the microsome fraction (range 0.31-0.46, median, 0.37 nmol/mg vs range 0.60-0.93, median 0.74 for group I, and range 0.63-1.22, median 0.91 for group III, reported as nmol/mg microsome protein; range 23.8-48.4, median 40.4 vs 66.6-130, median 81.8 for group I and range 59.0-117.1, median 77.1 for group III, reported as nmol/100 g body weight), and a prolongation of antipyrine half-life (146.4 vs 83.4 min for group I and 93.6 for group III) when compared with the rats of the two other groups. 3. Since the toxicity of acetaminophen depends on the production of a reactive metabolite by the cytochrome P450 system in the liver, we conclude that changes in this system brought about by exclusive sucrose ingestion for 42 h may explain the liver protection against the toxicity of a high dose of the drug even in the presence of a significant concomitant reduction in liver GSH levels

Effect of the intake of an exclusive sucrose diet on acetaminophen hepatotoxicity in rats

To test the effect of a sucrose diet on acetaminophen hepatotoxicity, 20 male Wistar rats were fasted and 20 were maintained exclusively on a sucrose diet ad libitum for 66 h. After 42 h, acetaminophen (1 g/kg) was administered through an orogastric tube to 10 fasted animals and to 10 animals on the sucrose diet, or intraperitoneally to the remaining animals. Animals were killed 24 h later and blood was collected for the measurement of alanine and aspartate aminotransferase activity and the liver was removel for macroscopic and microscopic examination. Plasma alanine and aspeartate aminotransferase levels were significantly lower (P<0.001) in all animals maintained on the sucrose diet. Macroscopic examination revealed parenchymatous necrosis in 90% (18/20) of the fasted animals but in none of the animals fed sucrosel. Microscopic examination confirmed the macroscopic findings and permited the detection of liver necrosis in one additional fasted animal. We conclude that ingestion of a sucrose diet protected the animals from the hepatotoxic effects of acetaminophen regardless of the route of administration of the drug

Diferenca de comprometimento do peristaltismo entre a parte superior e inferior do esofago na doenca de Chagas. / Difference of involvement of peristalsis between the upper and the lower part of the esophagus in Chagas disease

Os autores estudaram manometricamente o peristaltismo esofagico em 16 pacientes com esofagopatia chagasica com poucas alteracoes radiologicas. Em 6 foram observadas ondas peristalticas em todo o esofago e em 6 ondas sincronas. Em 4 pacientes observou-se ondas peristalticas na parte superior e ondas sincronas na parte inferior. A exemplo do que acontece em outras patologias que comprometem a motilidade esofagica, tambem na esofagopatia chagasica a perda do peristaltismo e mais precoce na parte inferior que na superior

Doenca de Crohn associada a sindrome de Turner. (Um possivel mecanismo fisiopatologico). / Crohn disease associated with Turner's syndrome. (A possible physiopathological mechanism)

Descreve-se o caso de uma paciente portadora de sindrome de Turner que desenvolveu diarreia cronica, fissuras anais e fistulas perianais e reto-vaginal. O estudo radiografico do ileo e a biopsia da mucosa retal confirmaram o diagnostico de doenca de Crohn. Como na maioria dos casos previamente descritos com associacao patologica semelhante, nessa paciente, a doenca intestinal iniciou-se na epoca em que acontece a crise puberal da hipofise. A falta de contra-regulacao pela gonada, em seguida a crise puberal da hipofise, produz um desiquilibrio hormonal com elevados niveis de FSH e LH. Supoe-se que este desiquilibrio hormonal possa ativar mecanismos imunopatogenicos relacionados a doenca de Crohn

A contratilidade esofatica em pacientes chagasicos com peristaltismo e com aperistalse. / The contractility of the esophagus in Chagas' patients with peristalsis and aperistalsis

Os autores estudaram manometricamente a contratilidade esofagica de 6 pacientes chagasicos com peristaltismo, 6 pacientes chagasicos com aperistalse (sincronos) e de 14 pacientes controles. A amplitude da onda de contracao foi menor na parte inferior do esofago, nos chagasicos com peristaltismo e com aperistalse. Observou-se uma tendencia, no esofago do chagasico, a apresentar a mesma amplitude e a mesma duracao da onda de contracao em todo seu corpo. Concluem que o esofago dos pacientes chagasicos com sinais de desnervacao no aparelho digestivo, que ainda nao apresentam dilatacao ou retarde de esvaziamento e mantem ondas peristalticas no exame manometrico, tem contratilidade diminuida na sua parte inferior

O comportamento do esfincter inferior do esofago durante a degluticao na esofagopatia chagasica. / Behavior of lower esophageal sphincter during deglutition in chagasic esophagopathy

Foram estudados 14 pacientes chagasicos cronicos sem acalasia e 14 controles quanto ao comportamento do esfincter inferior do esofago durante a degluticao. Foi utilizado o metodo manometrico, sem perfusao continua.Observou-se que, em media, o esfincter do esofago dos pacientes chagasicos tem menor comprimento na zona de alta pressao, demora mais a responder ao estimulo de degluticao e permanece aberto durante tempo menor que os controles