Adaptation of siblings of female rats given ethanol effect of N-acetyl-L-cysteine

Summary Ethanol administration to female rats before and during pregnancy resulted in decreased number of litters and increased activities of serum GOT, GPT and ALP. The hepatotoxicity of ethanol was indicated by the histological alterations both in the mother and siblings. There was increased levels of tissue lipids in mother and litters born to alcoholic rats. The concentration of TBARS in the liver and kidney were significantly increased in alcohol treated rats and their litters. The activities of the anti-peroxidative enzymes SOD and CAT were decreased on alcohol treatment in female rats. The glutathione content in liver and kidney decreased significantly in litters born to alcoholic rats.We have observed that the treatment with N-acetylcysteine offers protection against the toxic effect of alcohol in female rats during pregnancy and litters born to them. In N-acetylcysteine treated rats the number of litters as well as the average birth weight were close to that of control animals. Nacetylcysteine decreases the activities of serum GOT, GPT and ALP in female rats. We have also observed decreased levels of tissue lipids in mother and litters born to alcoholic rats given N-acetylcysteine when compared to alcoholic rats. The levels of TBARS in liver, kidney were also decreased both in mother and litter born to alcohol + N-acetylcysteine, while the activities of SOD and CAT were increased in liver of alcoholic rats given N-acetylcysteine when compared to alcoholic rats. Histopathological studies also showed the protective effect of N-acetylcysteine in both mother and litter in liver and kidney against alcoholic induced toxicity.     

Influences of crude extract of tea leaves,Camellia sinensis,on streptozotocin diabetic male albino mice

Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for diabetes mellitus. The aim of the present study was to investigate the hypoglycemic activity of the crude tea leaves extract on streptozotocin (STZ)-induced diabetic mice. The average body weight of animals with diabetes and their percentage changes of body weight gain after 15 and 30 days were significantly lower than that of the normal control mice. In diabetic mice, supplementation with tea leaves extract decreased the loss of body weight. After 15 and 30 days, significant increases in the levels of serum glucose, triglycerides, cholesterol, creatinine, urea, uric acid, glutamic pyruvic acid transaminase (GPT) and glutamic oxaloacetic acid transaminase (GOT) were noted in STZ-diabetic mice fed with normal diet. Also, the values of total protein in this group were statistically declined after 15 and 30 days. The levels of serum glucose and GPT were significantly elevated after 15 and 30 days in diabetic mice supplemented with tea leaves extract. Moreover, the level of serum GOT was notably increased after 30 days. Insignificant alterations were observed in the levels of serum triglycerides, cholesterol, total protein, creatinine, urea and uric acid in diabetic mice supplemented with tea leaves extract. Thus, the present results have shown that tea leaves extract has the antihyperglycemic, antihyperlipidemic, and antihyperproteinemic effects and consequently may alleviate liver and kidney damage associated with STZ-induced diabetes in mice.     

Effects of heat treated cells of intestinal lactic acid bacteria in rats fed a deoxycholic acid diet

Effects of the administration of heat treated cells of intestinal lactic acid bacteria were examined in rats fed a deoxycholic acid (DCA) diet. Male Wistar rats were given a 0.25% DCA diet with or without the heat treated cells of Enterococcus faecalis AD 1001 (EFH-1) or Lactobacillus reuteri AD 0002 (LRH-2) for 4 weeks. Abnormal increases in serum GOT, GPT, UN and lipoproteins were observed in the rats fed the DCA diet. Furthermore, severe lesions in the kidney as well as in the liver were found in these rats. On the contrary, the increases in serum GOT, UN, VLDL and LDL were significantly suppressed, and markedly fewer lesions in the liver and the kidney were observed in the rats fed the DCA diet plus EFH-1 or LRH-2.     

Acceleration of metabolism of stress-related substances by L-carnosine]

Liver dysfunction was produced in the rat by injecting CCl4 subcutaneously in the back twice a week, and the effects of L-carnosine (CAR) on the resulting liver injury were examined. When CCl4 was administered to 6-week-old rats for 9 weeks, GOT and GPT values increased, but these changes were suppressed in the group concomitantly treated with CAR, indicating a protective effect of the agent on liver function. No such preventive effects of CAR was observed in 40-week-old rats, but when the CCl4 administration was discontinued after 4 weeks, GOT and GPT decreased to normal levels within 1 week of discontinuation, indicating a therapeutic effect of CAR on hepatopathy. Based on these findings, we determined the cortisone beta-reductase activity in the rat liver. The increase in this enzyme activity in the group treated with CAR indicated acceleration of cortisone metabolism. Changes of blood cortisol level and cerebral and blood noradrenaline (NA) levels were studied by exposing 6-week-old rats to electric shocks at 30 V. Cortisol released into the circulation after the stress was quickly metabolized in the CAR group and the blood level normalized after 3 hours. Following the release of NA from the brain into the circulation, the NA concentration rapidly returned to the normal level both in the brain and the blood. CAR enhanced the liver function and accelerated the metabolism of stress-related substances also in aged animals. CAR, moreover, restored the RNA contents of the mouse spleen and the immunological abilities represented by PFC reaction, which are reduced by stresses such as forced immersion, fasting, and administration of MMC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Aloe vera (L.) Burm. fil. leaf gel and pulp extracts on kidney in type-II diabetic rat models

Significant degenerative changes were observed in the kidney tissue of untreated neonatal streptozotocin (n0STZ)-induced type-II diabetic rats. These degenerative changes were diminished in the kidney tissue of diabetic animals given glibenclamide and Aloe leaf gel and pulp extracts. Kidney lipid peroxidation levels were increased in diabetic rats compared to healthy rats; these levels were higher in rats treated with glibenclamide than in those which received Aloe extracts. Serum urea and creatinine levels were higher in diabetic rats in comparison to healthy rats. The administration of Aloe gel extract and glibenclamide decreased serum urea and creatinine levels in comparison to diabetic controls. Only A. vera leaf gel extract showed improvement both in histological and biochemical parameters suggesting a protective effect of A. vera on mild damage caused by type-II diabetes on kidney tissue.     

非酒精性脂肪肝大鼠PPARα基因表达及脂代谢和胰岛素水平的变化

目的观察非酒精性脂肪肝（NAFLD）大鼠肝组织中PPARα基因的表达,并用PPARct激动剂进行干预,探讨其与胰岛素抵抗、脂代谢紊乱的关系。方法大鼠随机分为①正常对照组、②高脂模型组、③PPARα激动剂干预组,利用高脂饮食建立大鼠非酒精性脂肪肝模型。12周后,检测大鼠血脂、肝功能、血糖、胰岛素水平及胰岛素抵抗指数;RT-PCR法分析PPARα基因的表达;观察肝脏的形态学改变。结果PPARa激动剂可降低NAFLD大鼠转氨酶、血脂水平及胰岛素抵抗指数,可促进NAFLD大鼠中PPARa基因的表达;肝脏形态学明显改善。结论PPARα激动剂能改善NAFLD大鼠脂质代谢紊乱,有明显的保肝降酶作用,具有适度的胰岛素增敏作用。PPARα及其配体在NAFLD发病机制及治疗中的进一步深入研究,将为临床防治NAFLD提供新的思路。     

Beneficial effect of somatostatin on galactosamine induced liver injury

The purpose of our investigation was to study the effect of somatostatin on acute experimental liver injury induced in rats by galactosamine (1.2 g/100 g body wt.). Somatostatin (125 micrograms/100 g body wt.) was administered subcutaneously in a protamine sulphate/ZnCl2 suspension either 2 h prior to the injection of galactosamine or 2 h and again 12 h following the injection. Serum transaminases (GOT, GPT) and serum concentrations of triiodothyronine and thyroxine were determined 28 h after the injection of galactosamine. Histology of the liver was performed by light microscopy. Our results showed that the administration of somatostatin significantly (P less than 0.02) reduced the elevation of GOT and GPT activity and diminished the degree of necrosis, and that although the administration of dibutyryl-cAMP (5 mg/100 g body wt.) intensified galactosamine induced liver injury, this effect of dibutyryl-cAMP could be completely prevented by somatostatin treatment. There was no difference in the serum concentrations of triiodothyronine and thyroxine in controls as compared to galactosamine and galactosamine plus somatostatin treated rats. At present the mechanism of this cytoprotection by somatostatin is unknown.     

Low-dose erythropoietin aggravates endotoxin-induced organ damage in conscious rats

Endotoxin shock can induce the production of several inflammatory mediators such as TNF-α, IL-6, and IL-1β, leading to multiple organ dysfunction and death. Erythropoietin (EPO) has been found to interact with its receptor (EPO-R), expressed in a wide variety of non-hematopoietic tissues, to induce a range of pleiotropic cytoprotective actions. We investigated the effects of low doses of EPO (300 U/kg, intravenous administration) on the physiopathology and cytokine levels in endotoxin shock in conscious rats. Endotoxin shock was induced by intravenous injection of Escherichia coli lipopolysaccharide (20 mg/kg) in conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 48 h after LPS administration. Levels of biochemical and cytokine parameters, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), and creatine phosphokinase (CPK) were measured at 0, 1, 3, 6, 9, 12, 18, 24, and 48 h after sepsis. Serum TNF-α, IL-6, and IL-1β level was measured at 1 h after sepsis. Endotoxin shock significantly increased blood GOT, GPT, BUN, Cre, LDH, CPK, TNF-α, IL-6, IL-1β levels, and HR, while it decreased MAP. EPO further increased the markers of organ injury (GOT, GPT, BUN, Cre, LDH, and CPK), inflammatory biomarkers (TNF-α, IL-6, and IL-1β) and did not affect MAP and HR after LPS. EPO disserved endotoxin shock-induced liver, kidney, lung, and small intestine damage in conscious rats. In conclusion, pre-treatment with low doses of EPO increased the release of TNF-α, IL-6, and IL-1β, along with aggravating endotoxin shock-induced markers of organ injury in conscious rats.     

Serum and liver enzyme changes in rats after short term exposure to dichlorvos

Rat serum and liver ICDH, OCT, GOT and GPT activities are significantly elevated 2-6 hr after i.p. injections of single doses (2.5 mg/kg body wt) of dichlorvos. ICDH, OCT, GOT and GPT activities are significantly increased in serum and liver of rats receiving daily injections (0.25 mg/kg body wt) for 7 days. Although liver SD is significantly elevated in the single and repeated dosage study, serum SD appears unaffected at these levels of dichlorvos toxicity. Changes in serum OCT activity estimations maybe a useful single parameter for screening pesticides for potential hepatotoxic effects in humans and farm animals.     

Evaluation of the toxicity of cypermethrin pesticide on organs weight loss and some biochemical and histological parameters

An increase in global food demand has resulted in a significant increase in the use of pesticides in agriculture. Synthetic pyrethroid pesticides account for over 30% of the global pesticide use; Pyrethroid pesticides were used preferably over organochlorines and organophosphates due to their high effectiveness, low toxicity to non-target organisms and easy biodegrability. It has widespread applications in agriculture through the world and as well in Algeria. Cypermethrin is one of the most insecticidal pyrethroids widely used in agriculture regions of Setif. to control wide range of insect pests in a variety of crops. The aim of this study is to investigate the effects of cypermethrin (Cyper-Ac 271 g/l from the active substance of the cypermethrin) on hematological, biochemical parameters, body weight loss, and histopathological study of some organs. Male mice weighing 30-40g were used, separated in 5 groups, n=6, two groups controls given vehicle (oil vegetable) and three experimental groups (Cypermetherin and vegetable oil). The animals were gavaged by 1/5 LD50 (LD50 = 485 mg/kg b/w) for 2 and 4 weeks respectively, and with 1/20 LD50 for 12 weeks, then the animals sacrificed at the end of the experiment.. Blood was collected. Enzyme activities were assayed in the plasma samples obtained. Glutamate oxaloacetate transaminase (GOT), Glutamate pyruvate transaminase (GPT), Alkaline phosphatase (ALPH) and Glucose. Red blood cells, (RBC), and white blood cells (WBC) were calculated too. The samples of liver and kidney were processed for histology. The results indicated a significant increase in transaminases GOT, GPT, and AlP. The decrease in Hb, RBC and WBC which are related to the immunity, this is probably due to cell lyses explain the effect of Cypermetherin on erythropoeisis. cypermethrin treatment exhibited severe histopathological changes, especially in the liver and kideney accompanied by weight loss of some organs. We conclude that cypermethrin induces oxidative stress and modifies biochemical parameters and histological aspects of liver and kidney.     

Pharmacokinetics of Glutamate–Oxaloacetate Transaminase and Glutamate–Pyruvate Transaminase and Their Blood Glutamate-Lowering Activity in Na?ve Rats

Traumatic brain injury (TBI) and stroke lead to elevated levels of glutamate in the brain that negatively affect the neurological outcomes in both animals and humans. Intravenous administration of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) enzymes can be used to lower the blood glutamate levels and to improve the neurological outcome following TBI and stroke. The objective of this study was to analyze the pharmacokinetics and to determine the glutamate-lowering effects of GOT and GPT enzymes in na?ve rats. We determined the time course of serum GOT, GPT, and glutamate levels following a single intravenous administration of two different doses of each one of the studied enzymes. Forty-six male rats were randomly assigned into one of 5 treatment groups: saline (control), human GOT at dose 0.03 and 0.06?mg/kg and porcine GPT at dose 0.6 and 1.2?mg/kg. Blood samples were collected at baseline, 5?min, and 2, 4, 8, 12, and 24?h after the drug injection and GOT, GPT and glutamate levels were determined. The pharmacokinetics of both GOT and GPT followed one-compartment model, and both enzymes exhibited substantial glutamate-lowering effects following intravenous administration. Analysis of the pharmacokinetic data indicated that both enzymes were distributed predominantly in the blood (central circulation) and did not permeate to the peripheral organs and tissues. Several-hour delay was present between the time course of the enzyme levels and the glutamate-lowering effects (leading to clock-wise hysteresis on concentration-effect curves), apparently due to the time that is required to affect the pool of serum glutamate. We conclude that the interaction between the systemically-administered enzymes (GOT and GPT) and the glutamate takes place in the central circulation. Thus, glutamate-lowering effects of GOT and GPT apparently lead to redistribution of the excess glutamate from the brain's extracellular fluid into the blood and can reduce secondary brain injury due to glutamate neurotoxicity. The outcomes of this study regarding the pharmacokinetic and pharmacodynamic properties of the GOT and GPT enzymes will be subsequently verified in clinical studies that can lead to design of effective neuroprotective treatment strategies in patients with traumatic brain diseases and stroke.     

Tiron administration minimizes the toxicity of vanadate but not its insulin mimetic properties in diabetic rats.

Although it has been reported that vanadate is effective in diminishing the expression of diabetes in the rat, the severe toxic side effects noted in the vanadate-treated animals suggest that chronic oral administration of vanadate argues against its use in human diabetes. The present study was conducted to evaluate the effects of the chelator Tiron on the mobilization of vanadium after administration of sodium metavanadate in the drinking water (0.20 mg/ml) of streptozotocin-induced diabetic rats for 35 days. Intraperitoneal treatment with Tiron (300 or 600 mg/kg) was initiated after three weeks of vanadate administration and continued for two weeks. The ameliorative effects of vanadium with respect to diabetes were not diminished by the administration of Tiron, but the accumulation of vanadium in kidney and bone was significantly decreased in the Tiron-treated groups and diabetes associated increases in serum GOT, GPT and cholesterol were diminished with Tiron treatment. It is concluded that the coadministration of metavanadate and Tiron may be of potential value for treatment of diabetes mellitus.     

Hepato-toxic effect of diuron in albino rats.

Tumour initiating/promoting effect of diuron, a widely used substituted urea herbicide, was studied in rats using liver tumour model. Chronic exposure to diuron at a dose of 250 mg/kg body wt resulted in high mortality and weight loss in treated animals. The animals which received diuron + HCH treatment showed an increase in size and weight of liver as compared to controls. Liver tumours were not observed in any of the treated group whereas some significant histological changes were seen in diuron treated rat liver. Diuron thus has been found to be hepatotoxic albeit neither tumour initiating nor promoting in rat liver tumorigenesis assay system.     

Hepatic calcium-binding protein regucalcin concentration is decreased by streptozotocin-diabetic state and ethanol ingestion in rats

The alteration in calcium-binding protein regucalcin in the liver and serum of rats with streptozotocin (STZ)-diabetic state or ethanol ingestion was investigated. STZ (6.0 mg/100 g body weight) was subcutaneously administered in rats, and 1 or 3 weeks later they were sacrificed by bleeding. Liver regucalcin mRNA levels were not clearly altered by the diabetic state, as evidenced by Northern blotting using regucalcin cDNA (0.9 kb of open reading frame). Based on enzyme-linked immunoadsorbent assay (ELISA) with rabbit-anti-regucalcin IgG, hepatic regucalcin concentration was decreased about 50% of control levels by STZ treatment. However, serum regucalcin concentration was not significantly altered by STZ treatment. Meanwhile, when rats ingested ethanol (10 and 30%) in the drinking water for 2 weeks, liver regucalcin mRNA levels were clearly increased, although hepatic regucalcin concentration was significantly decreased. Serum regucalcin concentration was not appreciably altered. Serum transaminases (GOT and GPT) activities were significantly increased at 1 or 3 weeks after STZ administration in rats, while their activities were not altered by ethanol ingestion. The present study demonstrates that hepatic regucalcin concentration is decreased independent of mRNA expression in the STZ-diabetes and during ethanol ingestion in rats.     

Effects of angiotensin II type 1 receptor blockade on the oxidative stress in spontaneously hypertensive rat tissues

The aim of this work was to investigate the production of oxidative damage in homogenized kidney, liver and brain of spontaneously hypertensive rats (SHR), as well as the involvement of angiotensin (Ang) II in this process. Groups of 12-week-old SHR and Wistar Kyoto rats (WKY) were given 10 mg/kg/day losartan in the drinking water during 14 days. Other groups of WKY and SHR without treatment were used as controls. The production of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) were determined. No significant difference in TBARS was observed between untreated SHR or WKY rats; GSH content was lower in the liver but higher in the brain of SHR compared to WKY rats. In tissues from the SHR group, SOD and Gpx activities were reduced, whereas CAT activity was slightly increased in kidney. TBARS levels did not change in WKY rats after losartan administration, but were reduced in SHR liver and brain. Losartan treatment decreased GSH content in WKY kidney, but increased GSH in SHR liver. The activity of the antioxidant enzymes was not modified by losartan in WKY rats; however, their activities increased in tissues from treated SHR. The lower activity of antioxidant enzymes in tissues from hypertensive rats compared to those detected in normotensive controls, indicates oxidative stress production. Ang II seems to play no role in this process in normotensive animals, although AT1 receptor blockade in SHR enhances the enzymatic activity indicating that Ang II is implicated in oxidative stress generation in the hypertensive animals.     

Time course effects of vanadium supplement on cytosolic reduced glutathione level and glutathione S-transferase activity

The influence of vanadium, an important dietary micronutrient, was evaluated on the cytosolic reduced glutathione (GSH) content and glutathione S-transferase (GST) activity in several rat target tissues. Supplementation of drinking water with vanadium at the level of 0.2 or 0.5 ppm for 4, 8, or 12 wk was found to increase the GSH level with a concomitant elevation in GST activity in the liver followed by small intestine mucosa, large intestine mucosa, and kidney. The results were almost dose-dependent and mostly pronounced with 0.5 ppm vanadium after 12 wk of its continuous supplementation. Neither the GSH level nor GST activity was significantly altered in forestomach and lung following vanadium supplementation throughout the study. The levels of vanadium that were found to increase the content of GSH and activity of GST in the liver, intestine, and kidney did not exert any toxic manifestation was evidenced from water and food consumption as well as the growth responses of the experimental animals. Moreover, these doses of vanadium did not impair either hepatic or renal functions as they did not alter the serum activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), sorbitol dehydrogenase (SDH), as well as serum urea and creatinine levels. All these results clearly indicate that vanadium under the doses employed in our study has a significant inducing role on GSH content with a concurrent elevation in GST activity in the liver and specific extrahepatic tissues without any apparent sign of cytotoxicity. This attribute of vanadium may have a greater importance in terms of biotransformation and detoxification of xenobiotics, including carcinogens. In addition, since the ability to afford an increment in the endogenous GSH-GST pool by anticarcinogenic natural substances has been found to correlate with their activity to inhibit neoplastic transformation, the trace element vanadium may be considered as a novel anticancer agent.     

Changes in amino acids and protein metabolism in Egyptian cobra (Naja haje) during hibernation

1. 1.Total protein, GOT, GPT, alkaline phosphatase and total free amino acid content in the brain, liver and kidney were studied in the hibernating, arousing and normothermic cobra (Naja haje).

2. 2.Tissues showed a decline in protein content which started in the prehibernating animals. At the low body temperatures in hibernation both synthesis and degradation would be reduced. The fall in protein content suggests synthesis is reduced more steeply than is degradation. Recovery of protein biosynthesis was demonstrated during arousal.

3. 3.In aroused animals, the levels of free amino acids in the tissues examined were higher than in hibernating ones or in normothermic controls studied in summer.

4. 4.A decline in GOT activity was recorded in the hibernating animals. The enzyme activity showed recovery on arousal. A similar trend was observed for the GPT activity in brain and kidney.

5. 5.The activity of alkaline phosphatase was also examined in the different tissues. The correlation of these changes to the different phases of hibernating cycle is discussed.

Characterization of the Impacts of Living at High Altitude in Taif: Oxidative Stress Biomarker Alterations and Immunohistochemical Changes

At high elevations, the human body experiences a number of pathological, physiological, and biochemical changes, all of which have adverse impacts on human health and organ vitality. This study aimed to investigate the alterations in the liver and kidney biomarkers, oxidative stress markers, gene expression, and cellular histology of rats maintained at high altitudes and normal sea level. A total of twenty male Wistar rats at 2 months of age were randomly assigned to two groups. The rats in group A were maintained at normal sea level in Jeddah, whereas rats in group B were maintained in an area in Taif 2600 m above sea level. After 2 months of housing, orbital blood samples were collected for the analysis of significant biochemical indicators of oxidative stress biomarkers of the liver and kidneys. Liver and kidney tissues from both groups were taken to examine the hepatorenal changes occurring at the biochemical, histological, immunohistochemical, and genetic levels. The results revealed substantial increases in the serum levels of liver and kidney biomarkers (GPT, GOT, urea, and creatinine) and decreases in the serum levels of antioxidant biomarkers (SOD, catalase, GSH, and NO). In parallel, the levels of the malondialdehyde (MDA) tissue damage marker and inflammatory cytokines (IL-1β, TNF-α, and IFN-γ) were increased in the high-altitude group compared to the normal sea level group. In addition, there were significant alterations in the oxidative and inflammatory status of rats that lived at high altitude, with considerable upregulation in the expression of hepatic VEGF, type 1 collagen, Cox-2, TNF-α, and iNOS as well as renal EPASI, CMYC, HIF-α, and EGLN-2 genes in the high-altitude group compared with controls housed at normal sea level. In conclusion, living at high altitude induces hepatorenal damage and biochemical and molecular alterations, all of which may serve as critical factors that must be taken into account for organisms living at high altitudes.     

Role of Amino Acid-catabolizing Enzymes in Urea Synthesis for Rats Treated with the Thyroid Hormone

The purpose of the present study was to determine whether the regulation of urea synthesis was mediated through the supply of nitrogen by amino acid-catabolizing enzymes and whether the concentration of acetylCoA would control the N-acetylglutamate concentration when the thyroid status was manipulated. Experiments were conducted on three groups of rats, each being given 6-propyl-2-thiouracil (PTU, thyroid inhibitor) without a triiodothyronine (T₃) treatment, or PTU + T₃, or neither PTU nor T₃ (control), respectively. The urinary excretion of urea, the liver concentration of N-acetylglutamate, and the hepatic activities of serine dehydratase, threonine dehydratase, alanine transaminase (GPT) and aspartate transaminase (GOT) in rats given PTU + T₃ were significantly lower than those in rats given PTU alone. The activity of glutamate dehydrogenase and the concentrations of free amino acids and acetylCoA in the liver of the PTU + T3-treated group were significantly higher than those in the group treated with PTU alone. These results suggest that the higher activity of amino acid-catabolizing enzymes in the hypothyroid (with PTU alone) rats is likely to stimulate urea synthesis.     

Interactions between Zn and Cu in LEC rats, an animal model of Wilson's disease

The effect of oral Zn treatment was studied in the liver and kidneys of 26 male Long-Evans Cinnamon (LEC) rats (mutant animals, 5 weeks old) in relation to both the interaction between Zn and Cu and the localisation and concentration of metallothionein (MT). Rats receiving 80 mg zinc acetate daily by gavage and control rats receiving no treatment were killed after 1 or 2 weeks. By immunohistochemical and analytical chemical techniques we revealed that treated rats had higher levels of MT in the hepatic and renal cells compared to untreated ones. Tissue Zn concentrations were significantly higher in treated rats compared to untreated whereas Cu concentrations decreased in the liver and kidneys as indicated by analytical chemical analyses. MT levels also decreased with treatment period. A histochemical procedure, obtained using autofluorescence of Cu-metallothioneins, confirms these findings: after 2 weeks, the signal decreased in both the liver and kidney sections. This gives a greater understanding of the mechanism of Cu metabolism in the two tissues considered. These results suggest that Zn acts both to compete for absorption on the luminal side of the intestinal epithelium and to induce the synthesis of MT.