Protein Malnourished Rats Research Articles

Diurnal Behavioral and Metabolic Patterns in Chronic Malnourished Rats

The temporal organization of behavioral patterns and metabolic activity was assessed in chronic low protein malnourished rats and their nutritional controls at 60 days of age. Spontaneous activity was video-recorded during 3 days for 10 min every hour and the frequency of exploration, grooming and ingestive behaviors was obtained, their basal metabolic rate was measured during 5 min every hour for one 24 h cycle. Rats of both nutritional groups showed a clear diurnal rhythmicity in all behavioral patterns, characterized by an increase of activity during the dark phase and a decrease during the light phase. Effects of malnutrition were selective and produced mainly a general decrease of the mean value and amplitude of the rhythm of ingestive behavior, as well as a bimodal pattern and rhythmic components of 12, 24 and 30 h according to autocorrelation and cosinor analysis. In both groups, the metabolic rate showed a bimodal diurnal rhythm, which fitted significantly to a 12 h period model and was not affected in malnourished rats. These data provide evidence that the circadian system is highly resistant to malnutrition. In malnourished rats rhythmicity of ingestive behavior was specifically affected, probably because the relation between metabolic processes and ingestive behaviors may be enhanced as a compensatory mechanism aimed to counteract the deficient diet composition.

Dietary Protein Level Regulates Expression of the Mitochondrial Branched-Chain Aminotransferase in Rats

The first step in the degradation of branched-chain amino acids (BCAA) is transamination catalyzed by the branched-chain aminotransferase (BCAT), which is located in extrahepatic tissues. Studies of the effect of dietary protein on BCAT activity have given contradictory results. Therefore, we established the levels of BCAT activity and mitochondrial BCAT (BCATm) mRNA expression in different organs and tissues of rats. We then determined the effect of different levels of dietary protein in well-nourished rats, the effect of feeding a 0.5% casein diet for 5 wk (protein-malnourished rats) and nutritional rehabilitation of these rats with different levels of dietary protein on BCAT activity and BCATm mRNA expression in selected tissues. Finally, the response of tissue BCAT activity and BCATm mRNA levels in rats fed a 10% casein diet and injected with glucagon (4 d) or hydrocortisone (7 d) was determined. The highest concentration of BCATm mRNA was found in stomach, followed by kidney, heart, muscle, brain, skin and lung. Low levels were found in intestine, and no BCATm mRNA was detectable in liver. Although BCAT activity was significantly higher in muscle, kidney and brain from rats adapted to consume a 50% casein diet for 7 h/d for 10 d than in rats fed 6, 18 or 35% casein diets, only muscle had significantly higher levels of BCATm mRNA. In protein-malnourished rats, BCAT activity and BCATm mRNA expression in kidney, muscle and heart were not different from those of rats with free access to an 18% casein diet. Nutritional rehabilitation of the protein-malnourished rats with 50% casein for 21 d significantly increased the BCAT activity and BCATm mRNA expression in muscle. Neither hydrocortisone nor glucagon injection affected BCAT activity or BCATm mRNA concentrations in rat kidney, muscle or heart. We conclude that the nutritional regulation of BCATm is extrahepatic, tissue specific and may involve transcriptional and post-translational mechanisms.

Effects of dietary protein and tumor necrosis factor on components of the insulin-like growth factor-I pathway in the colon and small intestine in protein-depleted rats

Intestinal cell growth is markedly affected by nutrient intake and the presence of cytokines. Since insulin-like growth factor-I (IGF-I) is an important hormone regulator of intestinal proliferation, this study examined the effects of dietary protein content and tumor necrosis factor (TNF) on mRNA levels of IGF-I, IGF-I receptor, IGF binding protein-3 (IGFBP-3), and IGFBP-4 and on the histology of the colon, jejunum, and ileum in protein-malnourished rats. After 2 weeks of feeding a 2% casein diet, rats continued on the 2% casein diet or were refed with a 20% casein diet and received daily intraperitoneal injections of either TNF (50 μg/kg) or saline for 4 days. The abundance of mRNA in the intestine was determined by RNA dot-blot analysis, and morphology measurements were performed by light microscopy. Simultaneous refeeding with the 20% casein diet and administration of TNF led to a modest increase in IGF-I and IGFBP-4 mRNA abundance in the colon. However, in the jejunum and ileum, refeeding had no effect but TNF caused a decrease in IGF-I and IGFBP-3 mRNA levels in malnourished rats. Refeeding with the 20% casein diet resulted in relatively modest histologic changes, which were greater in the colon versus the small intestine. The decreased magnitude of histologic changes in the order of the colon, ileum, and jejunum may reflect a response to a gradient of amino acid availability from intraluminal nutrients. These data demonstrate that TNF has distinct effects on colon and small intestine mRNA, but these mild changes had only a slight impact in the colon and did not translate into identifiable histologic changes in the small intestine. Combined protein restrictio and TNF administration had only a modest effect on intestinal mRNA levels and mucosal histology.

Effects of protein malnutrition on liver cytochrome p450s

Microsomal cytochrome P450s (CYPs) are the key enzymes that control the rate of drug metabolism. In turn, hepatic drug biotransformation is influenced by dietary macronutrients. We examined the effects of protein malnutrition on hepatic CYP1A and 3A in rats. Weanling male rats were fed protein-restricted diets with either 0.5% or 1.0% lactalbumin for 13 weeks. Control rats were fed similar diets but with 18% lactalbumin. Severe protein malnutrition resulted in rats fed the 0.5% and 1.0% lactalbumin diets as evidenced by stunting of growth, lowering of hematocrit and plasma albumin concentrations. Protein malnourished rats had a reduction in their hepatic microsomal concentrations only when expressed as per gm tissue but not as per protein concentration. Western blot analyses showed that protein malnutrition had no effect on hepatic CYP1A1 and only affected CYP1A2 at the most severe conditions (ie. in rats fed the 0.5% lactalbumin diet). Protein malnutrition however, led to >50% reduction in hepatic microsomal CYP3A proteins. Liver microsomal steroid metabolizing enzyme activities were evaluated by quantitation of specific metabolites formed following incubation with 4-C 14 progesterone and TLC separation. Protein malnutrition led to reductions in both 6β- and 16 α- progesterone hydroxylase, but did not affect either 17α-hydroxylase or 5α-reductase activity. Protein malnutrition, thus, modulates the various CYPs differently. Such changes in hepatic CYP concentrations might be the cause of altered drug metabolism accompanying protein malnutrition.

Altered adipocyte properties in the offspring of protein malnourished rats.

It is becoming well established that poor fetal and early postnatal growth can have long-term effects on adult health, including susceptibility to non-insulin-dependent diabetes mellitus, cardiovascular disease and hypertension. It is suggested that this results from poor nutrition during early life having permanent effects on the structure and metabolism of certain organs and tissues. In the present study we investigated the effect of a low-protein diet during pregnancy and lactation on adipocyte properties and glucose tolerance. Rat dams were fed on a diet containing either 200 (control) or 80 (low protein) g protein/kg during pregnancy and lactation. In addition cross-fostering techniques were employed to enable a separate evaluation of the prenatal and postnatal periods. All offspring were weaned onto a 200 g protein/kg diet at 21 d of age and then studied at 6 weeks of age. The mothers' protein supply during lactation appeared to be the most critical time window for long-term growth. In contrast, the offspring of mothers fed on a low-protein diet during pregnancy or lactation were significantly more glucose tolerant than controls, suggesting that both time windows can have long-term effects on glucose tolerance. In addition offspring of mothers fed on a low-protein diet during pregnancy or lactation had significantly smaller adipocytes than controls. However the largest reduction in adipocyte size was observed when there was a low-protein diet during both pregnancy and lactation. The amount of insulin receptor present in adipocyte membranes was increased in the three animal groups that had been exposed to the low-protein diets while levels of the insulin responsive glucose transporter (GLUT 4) were similar in adipocyte membranes from all groups.

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 submitted to protein malnutrition (6% protein in the diet rather than 20%) 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% (from 0.30 +/- 0.05 to 0.04 +/- 0.01) and 75% (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 half 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.

Role of bacterial adherence and the mucus barrier on bacterial translocation: effects of protein malnutrition and endotoxin in rats.

The purpose of the study was to investigate the potential relations between mucosal bacterial adherence, intestinal mucus and mucin content, and bacterial translocation. The attachment of bacteria to mucosal surfaces is the initial event in the pathogenesis of most bacterial infections that originate at mucosal surfaces, such as the gut. The intestinal mucus layer appears to function as a defensive barrier limiting micro-organisms present in the intestinal lumen from colonizing enterocytes. Consequently, studies focusing on the biology of bacterial adherence to the intestinal mucosa likely are to be important in clarifying the pathogenesis of gut origin sepsis. To explore the relations between intestinal bacterial adherence, mucus bacterial binding, and bacterial translocation, two models were used. One (protein malnutrition) in which profound alterations in intestinal morphology occurs in the absence of significant translocation and one (endotoxin challenge) in which bacterial translocation occurs and intestinal morphology is relatively normal. Protein malnutrition was not associated with bacterial translocation and measurement of enteroadherent, mucosally associated bacterial population levels documented that the total number of gram-negative enteric bacilli adherent to the ileum and cecum was less in the protein-malnourished rats than in the normally nourished animals (p < 0.01). Furthermore, there was an inverse relation between the duration of protein malnutrition and bacterial adherence to the intestinal mucosa (r = 0.62, p < 0.002). In contrast, after endotoxin challenge, the level of enteroadherent bacteria was increased and bacterial translocation was observed. The binding of Escherichia coli to immobilized ileal mucus in vitro was decreased significantly in protein-malnourished rats, whereas E. coli binding to insoluble ileal mucus was increased in the rats receiving endotoxin. This study indicates that the adherence of bacteria to the intestinal mucosal surface is an important factor in bacterial translocation, that intestinal mucus modulates bacterial adherence, and that increased levels of mucosally associated bacteria are associated with a loss intestinal barrier function to bacteria.

Glucose-Induced Insulin Secretion Is Impaired and Insulin-Induced Phosphorylation of the Insulin Receptor and Insulin Receptor Substrate-1 Are Increased in Protein-Deficient Rats

Malnutrition is related to diabetes in tropical countries. In experimental animals, protein deficiency may affect insulin secretion. However, the effect of malnutrition on insulin receptor phosphorylation and further intracellular signaling events is not known. Therefore, we decided to evaluate the rate of insulin secretion and the early molecular steps of insulin action in insulin-sensitive tissues of an animal model of protein deficiency. Pancreatic islets isolated from rats fed a standard (17%) or a low (6%) protein diet were studied for their secretory response to increasing concentrations of glucose in the culture medium. Basal as well as maximal rates of insulin secretion were significantly lower in the islets isolated from rats fed a low protein diet. Moreover, the dose-response curve to glucose was significantly shifted to the right in the islets from malnourished rats compared with islets from control rats. During an oral glucose tolerance test, there were significantly lower circulating concentrations of insulin in the serum of rats fed a low protein diet in spite of no difference in serum glucose concentration between the groups, suggesting an increased peripheral insulin sensitivity. Immunoblotting and immunoprecipitation were used to study the phosphorylation of the insulin receptor and the insulin receptor substrate-1 as well as the insulin receptor substrate-1-p85 subunit of phosphatidylinositol 3-kinase association in response to insulin. Values were greater in hind-limb muscle from rats fed a low protein diet compared with controls. No differences were detected in the total amount of protein corresponding to the insulin receptor or insulin receptor substrate-1 between muscle from rats fed the two diets. Therefore, we conclude that a decreased glucose-induced insulin secretion in pancreatic islets from protein-malnourished rats is responsible, at least in part, for an increased phosphorylation of the insulin receptor, insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase. These might represent some of the factors influencing the equilibrium in glucose concentrations observed in animal models of malnutrition and undernourished subjects.

Response threshold to aversive stimuli in stimulated early protein-malnourished rats.

Two animal models of pain were used to study the effects of short-term protein malnutrition and environmental stimulation on the response threshold to aversive stimuli. Eighty male Wistar rats were used. Half of the pups were submitted to malnutrition by feeding their mothers a 6% protein diet from 0 to 21 days of age while the mothers of the other half (controls) were well nourished, receiving 16% protein. From 22 to 70 days all rats were fed commercial lab chow. Half of the animals in the malnourished and control groups were maintained under stimulating conditions, including a 3-min daily handling from 0 to 70 days and an enriched living cage after weaning. The other half was reared in a standard living cage. At 70 days, independent groups of rats were exposed to the shock threshold or to the tail-flick test. The results showed lower body and brain weights in malnourished rats when compared with controls at weaning and testing. In the shock threshold test the malnourished animals were more sensitive to electric shock and environmental stimulation increased the shock threshold. No differences due to diet or environmental stimulation were found in the tail-flick procedure. These results demonstrate that protein malnutrition imposed only during the lactation period is efficient in inducing hyperreactivity to electric shock and that environmental stimulation attenuates the differences in shock threshold produced by protein malnutrition.

Altered muscle insulin sensitivity in the male offspring of protein-malnourished rats.

Insulin sensitivity of skeletal muscle was studied in male offspring of rat dams fed either a 20% (control) or 8% (low-protein) diet during pregnancy and lactation. Freshly isolated muscle strips took up more [3H]methylglucose from low-protein animals than from controls (19.2 +/- 2.5 and 4.26 +/- 0.45 nmol.min-1.mg muscle-1, respectively, P < 0.001). However, after a 60-min preincubation there was no significant difference in basal glucose transport (4.02 +/- 0.42 and 4.23 +/- 0.35 nmol.min-1.mg-1 for control and low-protein animals, respectively). Insulin (300 pM) had a significantly greater (P < 0.001) effect on stimulation of glucose transport into preincubated low-protein muscle strips than into controls (to 14.14 +/- 1.25 and 9.61 +/- 0.71 nmol.min-1.mg-1, respectively). There were no differences in total GLUT-4 protein content. However, subcellular fractionation revealed significantly (P < 0.001) more GLUT-4 in muscle plasma membranes of low-protein animals compared with controls. Insulin increased (P < 0.001) the GLUT-4 content of control plasma membranes but had no effect in low-protein animals. There were twofold more insulin receptors in low-protein muscle membranes compared with controls (2.35 +/- 0.17 x 10(11) and 1.28 +/- 0.10 x 10(11) and insulin receptors/mg muscle membrane protein, respectively, P < 0.01). These results suggest that programming of muscle insulin sensitivity can occur during fetal life.

Nutrient Metabolism in Pancreatic Islets from Protein Malnourished Rats

The metabolism ofD-[5-3H]glucose,D-[3,4-14C]glu- cose, [2-3H]glycerol,L-[U-14C]glutamine,L-[1-14C]leucine, andL-[U-14C]leucine was investigated in pancreatic islets isolated from either control rats or animals fed a low-protein isocaloric diet, containing 8% instead of 20% protein, during both fetal and postnatal life. In the latter animals, decreases in body weight, plasma insulin concentration, and insulinogenic index were associated with two major anomalies of islet nutrient metabolism. First, an imbalance between oxidative and anaerobic glycolysis was found in the islets of rats fed the low-protein isocaloric diet. It coincided with a decreased circulation in the glycerol phosphate shuttle, as judged by the generation of3HOH from [2-3H]glycerol, and was probably attributable to the deficiency of mitochondrial FAD-linked glycerophosphate dehydrogenase previously documented in islet homogenates of the rats fed low protein. Second, the transamination ofL-leucine to 2-ketoisocaproate was decreased in the low-protein-fed rats, while the oxidative decarboxylation of the 2-keto acid and the further catabolism of isovaleryl CoA occurred at normal rates when expressed relative to the initial transamination rate. These metabolic anomalies may account, in part at least, for the impairment of insulin release in protein malnutrition.

Altered regulation of hepatic glucose output in the male offspring of protein-malnourished rat dams.

Offspring of protein-malnourished rat dams have permanent alterations in hepatic enzyme activities associated with glucose homeostasis. Hormonal control of hepatic glucose output (HGO) was studied in male offspring of dams fed either a 20% (control) or 8% (low protein) protein diet during pregnancy and lactation. Glucagon (210 pM) stimulated HGO significantly more (P < 0.04) in controls (from 0.72 +/- 0.11 to 3.18 +/- 0.30 mumol.min-1.g liver-1) compared with low-protein animals (from 0.53 +/- 0.11 to 2.05 +/- 0.24 mumol.min-1.g liver-1). Insulin (1 nM) decreased (P < 0.001) HGO in controls to 2.39 +/- 0.37 mumol.min-1.g liver-1 after 10 min but increased HGO (to 2.82 +/- 0.40 mumol.min-1.g liver-1; P < 0.04) in low-protein rats. There were fivefold fewer (P = 0.01) glucagon receptors but a threefold increase (P < 0.05) in hepatic insulin receptor number in the low-protein rats, which was reflected by increased in insulin degradation (P < 0.001). The glucose transporter GLUT-2 was also raised threefold in the low-protein group (P < 0.001). The anomalous response to insulin indicates changes in its metabolic signaling, but normal insulin binding suggests that this alteration is a postreceptor event.

Effect of growth hormone on wound healing in protein-malnourished rats treated with corticosteroids.

Effect of growth hormone on wound healing in protein-malnourished rats treated with corticosteroids.

The effects of gossypol and chloroquine interaction on serum electrolytes of protein-malnourished rats

Serum sodium (Na), potassium (K), chloride (Cl), phosphate (Po), and calcium (Ca) were assayed in adult male Wistar rats fed a low protein diet (LP) and a normal protein diet (control, NP) and administered gossypol (GP) and chloroquine (CQ) alone and in combination (GPCQ), for 4 and 8 weeks. Gossypol was administered at 20 mg/kg body wt/rat/day in Goya oil and chloroquine at 5 mg/kg body wt/rat for 3 days/week in distilled water. The data, analyzed by two-way ANOVA, showed that the interaction had significant effects on the serum levels of Na, K, and Po (P<0.001) but not on chloride and calcium (P>0.05). Serum levels of sodium, potassium and phosphate in LP rats were significantly lower than in NP rats. In LP and NP rats, the levels of Na, K, and Po at 8 weeks were significantly higher than at 4 weeks; and GPCQ treatment produced significantly lower sodium levels in LP and NP rats, lower phosphate in LP rats and higher phosphate in NP-fed rats than GP or CQ administered alone. Potassium level in GPCQ was between levels in Gp- and CQ-treated rats. The administration of gossypol and chloroquine together may not adversely affect serum electrolytes in protein-malnutrition state any more than gossypol or chloroquine administered alone.

Dietary protein regimens and chronic ethanol administration effects on sodium- and proton-dependent solute uptake in rat intestine

The effect of feeding ethanol daily for 40 days has been studied on intestinal uptake of glucose, glycine, and leucine in rats fed control, 8% protein (LP), and 30% protein (HP) diets. Na +-dependent uptake of glucose and glycine both at pH 7.2 and pH 5.5 was significantly depressed ( p < 0.001) in ethanol or LP diet-fed animals and remained unaffected in HP-fed rats compared to the controls. But ethanol administration to protein-malnourished rats enhanced the Na +-linked glucose and glycine uptakes. Leucine uptake remained unaffected under these conditions. Glucose uptake remained unaltered whereas glycine uptake was reduced when ethanol was administered to rats given HP diet. In the absence of Na +, uptake of glucose, glycine, and leucine was more at acidic pH compared to that at pH 7.2 under all the experimental conditions investigated. Proton-linked uptake of solutes was unaffected by feeding ethanol, LP, or HP diet in rats. Thus, chronic ethanol feeding specifically depresses the Na +-dependent uptake of glucose and glycine. Dietary protein content modifies ethanol effects on intestinal solute uptake in rats.

Effects of an every other day rapid kindling procedure in prenatally protein malnourished rats

Prenatally protein malnourished ( 625) rats have been reported to require significantly more stimulations to attain a stage 5 seizure than well-nourished controls ( 2525) when using either a traditional or rapid every day, kindling procedure. In the present study, a rapid kindling procedure was utilized where both prenatally malnourished and control rats received every other day perforant path kindling (50 Hz, 10 s train) 12 times a day at 5-min intervals. Using this procedure, stage 5 seizures and a fully kindled state were attained in both nutritional groups at approximately the same rate. It is postulated that it is the every other day component of the present procedure which overcomes seizure-induced inhibition in the 625 subjects, thereby allowing them to attain stage 5 seizures at the same rate as controls.

Effect of growth hormone on wound healing in protein-malnourished rats treated with corticosteroids

This study was designed to evaluate the efficacy of human growth hormone (GH) in improving the tensile strength of wounds weakened by chronic protein malnourishment and corticosteroid (CS) administration. Eighty-six female Sprague-Dawley rats, weighing 80 to 100 g, were divided into five groups. Group 1 (control) received 23.4% protein chow for 8 weeks before surgery. Groups 2, 3, 4, and 5 received nonprotein chow on alternate days for the same duration. Groups 3 and 5 received prednisolone (2 mg/kg/d intramuscularly) for 3 weeks preoperatively and for 5 days postoperatively. Groups 4 and 5 were given GH (somatotropin, 1 IU/d) for 5 days postoperatively. All the animals underwent a precise 4-cm midline celiotomy. Wound testing was performed on the sixth postoperative day, after removal of the sutures. The bursting strength (BS, mean ± SD) for group 1 was 145 ± 16 mm Hg. The BS for groups 4 (137 ± 13 mm Hg) and 5 (134 ± 7 mm Hg) were significantly stronger than those for groups 2 (115 ± 15 mm Hg) and 3 (91 ± 16 mm Hg). The authors conclude that postoperative systemic GH restored the wound BS in protein-malnourished animals treated with CS, to the level of the normally nourished controls.

An analysis of spatial navigation in prenatally protein malnourished rats

Developing rats were either malnourished or adequately nourished during the prenatal period by feeding their dams diets of low (6% casein) or adequate (25% casein) protein content 5 weeks prior to mating and throughout pregnancy. All pups received adequate nutrition from the day of birth onwards. Male offspring were tested in one of two spatial navigation tests in the Morris water tank. In proximal-cue tests (postnatal days 16–20), the position of a platform, which provided a means to escape from swimming, was denoted by an obvious visual cue located directly on the platform. In distal-cue tests (postnatal days 20–27 and adult ages, days 70–71 and days 220–221), the escape platform was submerged below the surface of the water so that the rats were required to use extramaze visual cues to guide them to the platform. Neither proximal-cue nor distal-cue navigation was significantly impaired in the prenatally malnourished rats relative to controls, at any of the ages tested.

Prenatal protein malnutrition effects on the serotonergic system in the hippocampal formation: An immunocytochemical, ligand binding, and neurochemical study

Prenatally protein malnourished rats bom to dams maintained on a 6% casein diet during pregnancy and then fostered at birth to females on a 25% casein diet show adult alterations in hippocampal kindling and longterm potentiation and behavioral changes that all suggest dysfunction of hippocampal formation (HF). In the present investigation, compared to well-nourished controls, 220 day malnourished rats exhibited a decrease in the 5-HT fiber density in the dentate gyrus (DG) and CA3 subfield and, a 15–25% decrease 5-HT uptake sites assayed with [ 3H]-citalopram in CA3 andCA1. In malnourished rats, 5-HT 1A receptors assayed with [ 3H]8-OH-DPAT were decreased by 20% in CA3. Because most hippocampal subfields showed no 5-HT changes, hippocampal 5-HT levels determined via HPLC methods were similar in adult malnourished and control rats. These results suggest that there are localized changes in the 5-HT afferent system in the hippocampal formation of the 220 day prenatally protein malnourished rat. Considering the 5-HT afferent input to inhibitory intrahippocampal neurons, the decreased 5-HT plexus may result in increased inhibition within specific hippocampal subfields despite overall normal levels of 5-HT in the total HF.

Growth hormone reverses impaired wound healing in protein-malnourished rats treated with corticosteroids

Corticosteroid (CS) administration amplifies the inhibitory effect of protein malnutrition (PM) on wound healing. Abdominal surgery in protein malnourished patients receiving corticosteroids (eg, advanced malignancy, transplant recipients) may be complicated by wound dehiscence or anastomotic breakdown. Although preoperative parenteral nutrition can reduce the incidence of these complications, this is not possible in patients requiring urgent surgical intervention. In a previous report we demonstrated that postoperative growth hormone (GH) administration could restore normal wound healing in PM rats. This study evaluates the effect of GH on wound healing in PM rats treated with CS. Forty-eight female Sprague-Dawley rats weighing 180 to 210 g were divided into four groups: (1) normally nourished; (2) PM only; (3) PM + CS; and (4) PM + CS + GH. PM rats (groups 2 to 4) received 5.5% protein chow every other day for 8 weeks. Control rats (group 1) received 23.4% protein chow for the same duration. Group 3 and 4 rats received prednisolone (2 mg/kg, intramuscularly) during the last 3 weeks of PM. All animals underwent precise 5-cm midline celiotomies. Postoperatively, rats in all groups were given 23.4% protein chow. Group 3 and 4 rats continued to receive CS postoperatively. Group 4 rats were given GH (0.5 mg/d, intraperitoneally) postoperatively for 5 days. Wound testing was performed on the 6th postoperative day after removal of the sutures. A balloon inserted into the peritoneal cavity through the vagina was gradually inflated. The pressure at which the wound disrupted was recorded as the wound bursting strength. The results of this study suggest that (1) postoperative GH restored the wound bursting strength in PM animals treated with CS to that seen in normally nourished controls, and (2) the wound healing enhancement of GH occurs at an early stage when compromised abdominal wounds are most likely to dehisce.