Intestinal enzymes during malnutrition & infection in rabbits.

BACKGROUND & OBJECTIVES: Malnutrition plays an important role in the intestinal absorption of nutrients. However, reports are not consistent whether intestinal enzymes are decreased in the presence of malnutrition. It is also not clear whether simultaneous presence of malnutrition and infection adds to the problem of malabsorption of nutrients. The aim of the present study was to determine intestinal functions in terms of concentrations of disaccharidase enzymes during diarrhoea and protein energy malnutrition. METHODS: Concentrations of three disaccharidase enzymes, namely maltase, sucrase and lactase were measured in nine energy-restricted and five control rabbits during diarrhoea induced by rabbit diarrhoeagenic Escherichia coli (RDEC-1). Malnutrition was achieved in the rabbit model by feeding the animals for 30 days with half the amount of food fed to well-nourished control rabbits. Both the energy-restricted and the control groups were challenged by RDEC-1. Diarrhoea occurred on day 1-7 after administration of the strain. After onset of diarrhoea, both groups of rabbits were sacrificed and their intestinal mucosa was examined to determine the concentration of lactase, maltase and sucrase. RESULTS: The energy-restricted animals and controls did not differ significantly for concentrations (units/mg proteins) of lactase (0.65 +/- 0.28 vs 0.56 +/- 0.17 ), maltase (6.20 +/- 2.70 vs 6.47 +/- 1.90) and sucrase (5.42 +/- 2.30 vs 5.13 +/- 1.40) measured during acute infectious diarrhoea. INTERPRETATION & CONCLUSION: The results suggested that the enzymatic functions of the intestinal brush border were not statistically different during diarrhoea among malnourished rabbits compared with their well-nourished counterparts.

Efecto de la diarrea sobre la utilización de nutrientes en ratas con desnutrición proteico-calórica o proteica / Effect of diarrhea on nutrient utilization in protein deficient or protein-calorie deficient rats

La diarrea magnifica los efectos de la desnutrición. En consecuencia, aquí se estudió el efecto de la diarrea sobre dos tipos de desnutrición (proteica y proteico-calórica). El experimento incluyó 42 ratas jóvenes de la cepa Sprague Dawley que se distribuyeron en tres grupos (14 ratas/grupo). Durante los primeros 16 días del experimento, el primer grupo recibió una dieta control ad-libitum, el segundo recibió la misma dieta pero su consumo se redujo en un 50% y el tercer grupo recibió una dieta deficiente en proteína. Al final de este período había ratas bien nutridas (controles) y con desnutrición proteica y calórico-proteica. Luego, a la mitad de estas ratas en cada grupo, se les produjo diarrea con lactosa y todas las ratas continuaron con su dieta y el régimen de alimentación preasignado durante una semana. Así, durante este período había ratas controles así como con deficiencia proteica o calórico-proteica que tenían diarrea y grupos idénticos que no tenían diarrea. Los resultados mostraron que la diarrea causó una disminución del consumo y del crecimiento en las ratas del grupo control y deficiente en proteína. Sin embargo, el grupo con deficiencia calórico-proteica no redujo su consumo ni disminuyó su crecimiento en respuesta a la diarrea. La consecuencia de esto fue que la diarrea produjo desnutrición en el grupo control y aumentó la desnutrición en el grupo deficiente en proteína, pero no tuvo un efecto adicional en el grupo con deficiencia calórico-proteica. Además, la reducción en la absorción aparente del nitrógeno y de la grasa asociada con la diarrea, fue mayor en las ratas deficientes en proteína. Este grupo también presentó las actividades más bajas de disacaridasas intestinales. Esto resultados muestran que la diarrea tiene un efecto negativo mayor en ratas con deficiencia proteica que con deficiencia calórico-proteica.

Diarrhea increases the effects of malnutrition. Accordingly, the effect of diarrhea on two types of malnutrition (protein deficiency and protein-calorie deficiency) was studied. The experiment included 42 young Sprague Dawley rats. The rats were distributed into three groups with 14 rats per group. During the first 16 of the experiment, the first group was fed a control diet ad libitum, the second received the same diet but with food intake reduced in 50% whereas the third group was offered a protein deficient diet. Thus, at the end of this period there were well-fed rats (control), as well as protein and protein-calorie malnourished rats. Then one half of the rats in each group were given lactose to produce diarrhea and all rats continued with their previously assigned diet and feeding regime during one more week. Therefore, during this period there were control rats, protein deficient rats and protein-calorie deficient rats with and without diarrhea. The results showed that diarrhea caused a substantial reduction in food intake and growth in the well-fed rats and also in the group fed the protein deficient diet. However, the protein-calorie deficient group did not reduce its intake nor its growth rate. As a result, diarrhea caused malnutrition in the control group and increased malnutrition in the protein deficient but it did not have an additional effect in the protein-calorie deficient rats. The apparent absorption of lipids and nitrogen measured in these rats showed that the absorption reduction caused by diarrhea was more pronounced in the protein deficient group. This group also had the lowest activities of intestinal disaccharidases. These results showed that diarrhea had a more detrimental effect in protein deficient than in protein-calorie deficient rats.

Effects of malnutrition on the digestive enzymes of the large bowel of young rhesus monkeys.

The aim of the present study was to investigate the effect of mild-to-moderate protein-energy malnutrition (PEM) and rehabilitation on the digestive enzymes of the large bowel in young rhesus monkeys. The presence of these enzymes has already been reported in the large bowel by many authors. The activities of the digestive enzymes, i.e. lactase, sucrase, maltase, trehalase, glucoamylase, leucine aminopeptidase, alkaline phosphatase and gamma-glutamyl transpeptidase, from different parts of the large bowel were determined in 6 controls, 6 PEM and 6 rehabilitated young rhesus monkeys. These monkeys had been used to study the effect of malnutrition on the small intestine and the results have already been published. There was a significant decrease in the sucrase in the ascending colon (p < 0.05); maltase in all the parts of the large bowel (p < 0.05); and glucoamylase activities (p < 0.05) in the caecum segment of the large bowel in the PEM group. The activity of other enzymes, i.e. lactase, trehalase, alkaline phosphatase, gamma-glutamyl transpeptidase and leucine aminopeptidase, was unaffected in the PEM group. The changes in the enzyme activities recovered on rehabilitation of 21 weeks. The result of this study suggest that even mild-to-moderate malnutrition affects the enzyme activity of the large bowel, which recovers on rehabilitation.

Effects of pregnancy and protein-energy malnutrition on monooxygenase O-dealkylation activity in rat liver microsomes

Xenobiotic metabolism is influenced by a variety of physiological and environmental factors including pregnancy and nutritional status of the individual. Pregnancy has generally been reported to cause a depression of hepatic monooxygenase activities. Low-protein diets and protein-energy malnutrition have also been associated with a reduced activity of monooxygenases in nonpregnant animals. We investigated the combined effects of pregnancy and protein-energy malnutrition on liver monooxygenase O-dealkylation activity. On pregnancy day 0 rats were assigned at random to a group fed ad libitum (well-nourished, WN) or to a malnourished group (MN) which received half of the WN food intake (12 g/day). WN and MN rats were killed on days 0 (nonpregnant), 11 or 20 of pregnancy and ethoxy- (EROD), methoxy- (MROD) and penthoxy- (PROD) resorufin O-dealkylation activities were measured in liver microsomes. Only minor changes in enzyme activities were observed on pregnancy day 11, but a clear-cut reduction of monooxygenase activities (pmol resorufin min-1 mg protein-1) was noted near term (day 0 vs 20, means + or _ SD, Student t-test, P<0.05) in WN (EROD: 78.9 + or - 15.1 vs 54.6 + or - 10.2; MROD: 67.8 + or - 10.0 vs 40.9 + or - 7.2; PROD: 6.6 + or - 0.9 vs 4.3 + or - 0.8) and in MN (EROD: 89.2 + or - 23.9 vs 46.9 + or - 15.0; MROD: 66.8 + or - 13.8 vs 27.9 + or - 4.4; PROD: 6.3 + or - 1.0 vs 4.1 + or - 0.6) dams. On pregnancy day 20 MROD was lower in MN than in WN dams. Malnutrition did not increase the pregnancy-induced reduction of EROD and PROD activities. Thus, the present results suggest that the activities of liver monooxygenases are reduced in near-term pregnancy and that protein-energy malnutrition does not alter EROD or PROD in pregnant rats

Deficiencia proteica: impacto sobre el timo de ratas en crecimiento / Protein deficiency: effect of thymus of growing rats

Se analiza las consecuencias provocadas por desequilibrios nutricionales sobre el contenido de DNA y la actividad de las enzimas ADA y PNP en timo de ratas en crecimientos. Ratas Wistar al destete fueron alimentadas con: 1- dieta libre de proteínas hasta asemejar cuadros de malnutrición proteica leve, moderada y severa; 2- dieta conteniendo harina de maíz en baja concentración (6,5 por ciento). La subnutrición durante la lactancia se obtuvo duplicando la camada (12-14 crías por madre). Como controles se utilizaron ratas bien nutridas de igual edad, que desde el destete recibieron dieta stock. Al finalizar la experiencia, se les extrajo el timo (Pt)(mg). Se determinó DNA (mg/órgano), el número de núcleos, el tamaño celular- Pt(mg)/No. de Núcleos- y la actividad de las enzimas ADA y PNP (umol de ácido úrico x 10 - 1/P)(P=Pt(mg) /P corporal 0.75). Los resultados muestran que tanto la subnutrición durante la lactancia, como la malnutrición proteica al destete y la administración de dieta de baja calidad, afectan la proliferación celular en el timo, Sólo la carencia de proteína o su baja calidad, aumenta la actividad de ADA y PNP

Effect of protein malnutrition on the glycolytic and glutaminolytic enzyme activity of rat thymus and mesenteric lymph nodes

The activity of important glycolytic enzymes (hexokinase, phosphofructokinase, aldolase, phosphohexoseisomerase, pyruvate kinase and lactate dehydrogenase) and glutaminolytic enzymes (phosphate-dependent glutaminase) was determined in the thymus and mesenteric lymph nodes of wistar rats submited to protein malnutrition (6 percent protein in the diet rather than 20 percent) from conception to 12 weeks after birth. The wet weight (g) of the thymus and mesenteric lymph nodes decreased due to protein malnutrition by 87 percent (from 0.30 + 0.05 to 0.04 + 0.01) and 75 percent (0.40 + 0.04 to 0.10 + 0.02), respectively. The protein content was reduced only in the thymus from 102.3 + 4.4 (control rats) to 72.6 + 6.6 (malnourished rats). The glycolytic enzymes were not affected by protein malnutrition, but the glutaminase activity of the thymus and lymph nodes was reduced by halfing in protein-malnourished rats as compared to controls. This fact may lead to a decrease in the cellularity of the organ and thus in its size, weight and protein content.

Glyoxalase I activity in erythrocytes from severely malnourished children

The enzyme glycoxalase I (glyox I) is involved in metabolic detoxification, and requires glutathione (GSH) as a cofactor. Given the low concentration of whole blood GSH in children with oedematous malnutrition, it is possible that the function of this pathway may be compromised in these children. Glyox I activity was therfore assayed in erythocytes taken from 133 severely malnourished children and 21 age-matched controls. The mean values (ñSEM) for the marasmic group (marasmus: 105 ñ 4/u/gm Hb) and the group with kwashiorkor (Kwash: 103 ñ 4/u/gm Hb) were not significantly different from controls (cont: 104 ñ 2u/gm HB)>. In the group with marasmic-kwashiorkor (M-K: 88 ñ 4u/g Hb) Glyox I activity was significantly lower in controls (p < 0.005), as well as in children with marasmus (p < 0.005), and kwashiorkor (p < 0.05). Enzyme activity was lower than normal in 45 per cent of the MK group. Seven children died subsequent to admission; in five cases Glyox I activities were exceedingly low. There was a weak positive correlation between Glyox I activity and whole blood levels of GSH (r=0.215). We conclude that Glyox I activity is relatively unaffected in malnutrition, except in those with M-K and especially those who do not survive the acutely malnourished state

Cambios inducidos por rehabilitación nutricional temprana en la vía serotoninérgica cerebral activada por desnutrición gestacional / Changes induced by nutritional neonatal rehabilitation in the brain serotonergic path activated by gestational malnourished

Introducción. Se ha demostrado que la desnutrición gestacional produce desde la etapa fetal una aceleración de la síntesis de 5-hidroxitriptamina cerebral (5-HT), secundaria a un aumento de la afinidad de la triptófano-5-hidroxilasa (T5-H) por el L-triptófano (L-Trp) y una mayor capacidad de fosforilación. Estos hallazgos han sugerido un cambio conformacional de la enzima durante el desarrollo cerebral como mecanismo principal que explique la aceleración de la síntesis de 5-HT. El objetivo de este trabajo fue evaluar los diferentes cambios que se producen en el cerebro de las ratas desnutridas durante la gestación y que al nacer son sometidas a un esquema de rehabilitación nutricia, con el propósito de obtener información que nos permita apoyar la hipótesis de que el mecanismo de activación de la síntesis de 5-HT cerebral es debida a un cambio estructural de la T5-H. Material y Métodos. Se seleccionaron ratas cepa Wistar, adaptadas a condiciones ambientales estándar. Al término de este período se formaron dos grupos: uno con desnutrición proteínico-calórico (D) y el otro control (C). Las hembras fueron pareadas con machos normales. Al nacimiento las crías de ambos grupos fueron mezcladas y redistribuidas al azar a madres del mimsmo grupo; ademas se realizó un entrecruzamiento de las crías de estos grupos para formar dos subgrupos; el desnutrido recuperado (DR) y el desnutrido en la lactancia (DL). A las edades de 1, 10, 15 y 21 días, se obtuvo el encéfalo para los ensayos bioquímicos. Además se realizaron curvas de peso corporal, cerebral y de la longitud céfalo-sacra. Resultados. Los grupos D y DL mostraron un retraso significativo del crecimiento corporal, cerebral y de la longitud céfalo desde el primer día hasta los 21 días de edad en comparación a los controles. El mismo patrón se observó en las proteínas tisulares. El grupo DR alcanzó una recuperación física a los 15 días de edad. La actividad de la enzima en los desnutridos mostró un aumento significativo en todas las edades estudiadas; la misma elevación significativa persistió en el grupo DR hasta los 21 días en comparación al grupo control y una elevación significativa en la concentración de 5-HT. Conclusiones: Los resultados confirman que la desnutrición gestacional y posnatal producen una deficiencia en la composición corporal, cerebral y una aceleración en la síntesis de 5-hidroxitriptamina. Además apoyan el hecho de que la rebilitación nutricional neonatal produce una recuperación en la composición corporal. Sin embargo los hallazgos de que el L-Trp cerebral se normalice en el animal rehabilitado, de que la actividad de la T5-H permanezca elevada y persista un aumento en la síntesis de neurotransmisor, 5-HT, apoya indirectamente la hipótesis de que el mecanismo de activación de esta importante vía biosintética cerebral, es posiblemente debiido a un cambio relacionado a la estructura de la triptófano-5-hidroxilasa inducido por la desnutrición ontogénica. Desnutrición gestacional; 5-hidroxitriptamina; cerebro; rehabilitación nutricional; triptófano-5-hidroxilasa

Jejunal disaccharidases in protein energy malnutrition and recovery.

The jejunal disaccharidases, sucrase, maltase and lactase, were determined in jejunal biopsies obtained from 43 malnourished children and 10 controls. In the study group, 63% were girls and 93% had severe malnutrition. Lactase activity was significantly reduced in third and fourth degree malnutrition (p < 0.05 and p < 0.005, respectively), but maltase activity was significantly reduced only in the fourth degree malnutrition (p < 0.01). After recovery, maltase and sucrase activities showed a marginally significant increase (p = 0.06), where lactase showed no significant increase (p > 0.05). We conclude that jejunal disaccharidase activity decreases significantly with increasing severity of malnutrition, lactase being the most severely affected and the last to recover.

Serum enzyme abnormalities in protein energy malnutrition.

Six serum enzymes, alkaline phosphatase, cholinesterase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase were studied in 30 cases of protein energy malnutrition (PEM). The mean serum values of alkaline phosphatase, cholinesterase and lactate dehydrogenase in cases of PEM were significantly lower than the controls, lowering being maximum in PEM Grade IV. The mean serum values of aspartate aminotransferase and alanine aminotransferase in patients with PEM were significantly higher than the controls. The mean serum values of gamma-glutamyl transpeptidase showed similar significant rise in all but PEM Grade IV. The degree of increase in the serum values of these three enzymes were maximum in cases with PEM Grade I. These findings suggest that abnormalities in blood levels of these enzymes occur in any form of PEM and these are related to the severity of the disease.

Effects of undernutrition during suckling on ATP and ADP hydrolysis by synaptosomes from the cerebral cortex of adult rats

Early undernutrition can cause permanent functional changes in the nervous system. Alterations in enzymes involved in neurotransmiter metabolism have been reported to result from early undernutrition. In a previous study, we demonstrated that undernutrition during suckling decreaseATP and ADP hydrolysis by synaptosomes from cerebral cortex by abouth 20% of the value found in 20-day-old well-nourished rats (j.B.T. Rocha, C.F. Melo, J.J.F.Sarkis and R.D. Dias, British Journal of Nutrition, 63:273-283, 1990). In the present study, we investigated whether this deficit persists in synaptosomes from cerebral cortex of nutritionally rehabilitated adult rats. rats were undernourished from birth to 25 days of life by feeding their dams a 7% casein (w/w) diet, while well-nourished offspring were fed by mothers maintained on a 28% casein diet. In contrast to the results previously obtained in young rats, the synaptosomes obtained from the cerebral cortex of early undernourished adult rats hydrolyzed ATP and ADP more efficiently than did those obtained from well-nourished rats. Specific activity (nmol min-1 mg protein-1, mean ñ SD) was 114.9ñ9.5 for undernourished rats (N=8) for ATP, and 50.4ñ6.1 (N=8) vs 38.8ñ4.5 (N=8) for ADP. These results suggest that the deficits found in young rats disappear in rehabilitation adult rats

Effect of protein-calorie malnutrition on drug metabolising enzymes in rat liver.

Drugs are chiefly metabolised in the liver usually in two phases, viz. oxidation and conjugation. The present study was undertaken to investigate the effect of protein-calorie malnutrition (PCM), rehabilitation and effect of phenobarbitone on the hepatic drug metabolising enzymes in weanling albino rats, fed on a semisynthetic diet containing 18% or 0.5% protein. The two representative enzymes of oxidation and conjugation employed were aminopyrine N-demethylase and bilirubin UDP-glucuronyl transferase, respectively. The study revealed that PCM severely impairs oxidative drug metabolising enzyme but less so in conjugation stage. On refeeding 18% protein diet, drug metabolising enzymes returned to normal within 2-3 weeks. Phenobarbitone administration increased the activities of drug metabolising enzymes.