Amino Acid Metabolism In Rats Research Articles

Coffee Leaf Tea Extracts Improve Hyperuricemia Nephropathy and Its Associated Negative Effect in Gut Microbiota and Amino Acid Metabolism in Rats.

Hyperuricemia nephropathy (HN) is a metabolic disease characterized by tubular damage, tubulointerstitial fibrosis, and uric acid kidney stones and has been demonstrated to be associated with hyperuricemia. Coffee leaf tea is drunk as a functional beverage. However, its prevention effects on HN remain to be explored. This study showed that coffee leaf tea extracts (TE) contain 19 polyphenols, with a total content of 550.15 ± 27.58 mg GAE/g. TE decreased serum uric acid levels via inhibiting XOD activities and modulating the expression of urate transporters (GLUT9, OAT3, and ABCG2) in HN rats. TE prevented HN-induced liver and kidney damage and attenuated renal fibrosis. Moreover, it upregulated the abundance of SCFA-producing bacteria (Phascolarctobacterium, Alloprevotella, and Butyricicoccus) in the gut and reversed the amino acid-related metabolism disorder caused by HN. TE also decreased the circulating LPS and d-lactate levels and increased the fecal SCFA levels. This study supported the preliminary and indicative effect of coffee leaf tea in the prevention of hyperuricemia and HN.

Neuroprotective Effect of White Nelumbo nucifera Gaertn. Petal Tea in Rats Poisoned with Mancozeb.

Nelumbo nucifera Gaertn. (N. nucifera) tea is used as food and folk medicine to reduce toxicity in Southeast Asia. Mancozeb (Mz) is used for controlling fungi in agriculture and contains heavy metals. This study aimed to examine the effect of white N. nucifera petal tea on cognitive behavior, hippocampus histology, oxidative stress, and amino acid metabolism in rats poisoned with mancozeb. Seventy-two male Wistar rats were divided into nine groups (n = 8 in each). Y-maze spontaneous alternation test was used to assess cognitive behavior, and amino acid metabolism was investigated by nuclear magnetic resonance spectroscopy (1H-NMR) from blood. There was a significant increase in relative brain weight in the Mz co-administered with the highest dose (2.20 mg/kg bw) of white N. nucifera group. The levels of tryptophan, kynurenine, picolinic acid, and serotonin in blood showed a significant decrease in the Mz group and a significant increase in the Mz co-administered with low dose (0.55 mg/kg bw) of white N. nucifera group. However, there was no significant difference in cognitive behavior, hippocampus histology, oxidative stress, and corticosterone. This study demonstrated that a low dose of white N. nucifera petal tea has a neuroprotective effect against mancozeb.

Effects of histidine supplementation on amino acid metabolism in rats.

Histidine (HIS) is investigated for therapy of various disorders and as a nutritional supplement to enhance muscle performance. We examined effects of HIS on amino acid and protein metabolism. Rats consumed HIS in a drinking water at a dose of 0.5 g/l (low HIS), 2 g/l (high HIS) or 0 g/l (control) for 4 weeks. At the end of the study, the animals were euthanized and blood plasma, liver, soleus (SOL), tibialis (TIB), and extensor digitorum longus (EDL) muscles analysed. HIS supplementation increased food intake, body weight and weights and protein contents of the liver and kidneys, but not muscles. In blood plasma there were increases in glucose, urea, and several amino acids, particularly alanine, proline, aspartate, and glutamate and in high HIS group, ammonia was increased. The main findings in the liver were decreased concentrations of methionine, aspartate, and glycine and increased alanine. In muscles of HIS-consuming animals increased alanine and glutamine. In high HIS group (in SOL and TIB) increased chymotrypsin-like activity of proteasome (indicates increased proteolysis); in SOL decreased anserine (beta-alanyl-N1-methylhistidine). We conclude that HIS supplementation increases ammonia production, alanine and glutamine synthesis in muscles, affects turnover of proteins and HIS-containing peptides, and increases requirements for glycine and methionine.

Potential hepatoxicity risk of the shell of Herpetospermum caudigerum Wall in rats based on 1H-NMR metabonomics

The Herpetospermum caudigerum Wall (HCW) is a traditional Tibetan medicine and is widely used in clinical practice. However, the shell of the HCW (SHCW) has rarely been studied, and some researchers have suggested that the SHCW may be toxic. Therefore, in this study, SHCW was administered to rats at two doses (0.1 and 0.33 g/kg) once a day for 21 days. The hepatic stimuli induced by SHCW in rats were investigated for the first time by 1H-NMR-based metabolomics combined with histopathological observation and biochemical detection. Histopathological sections showed a certain degree of hepatocyte edema and hepatic sinus congestion in the liver tissue of the rats in the drug-administered group. Serum biochemical indicators revealed a significant increase in ALT, AST, and MDA, and a significant decrease in SOD. Metabolomic results showed that the metabolites in rats were changed after gavage administration of extracts from SHCW. By multivariate statistical analysis and univariate analysis, it was found that SHCW could cause the disorder of energy metabolism, oxidative stress and amino acid metabolism in rats, leading to liver damage. This comprehensive metabolomics approach demonstrates its ability to describe the global metabolic state of an organism and provides a powerful and viable tool for exploring drug-induced toxicity or side effects.

A snapshot of Chinese Medicine practice in Australia over a 10 year period (2006–2016): Moving towards integrative clinical care

The Herpetospermum caudigerum Wall (HCW) is a traditional Tibetan medicine and is widely used in clinical practice. However, the shell of the HCW (SHCW) has rarely been studied, and some researchers have suggested that the SHCW may be toxic. Therefore, in this study, SHCW was administered to rats at two doses (0.1 and 0.33 g/kg) once a day for 21 days. The hepatic stimuli induced by SHCW in rats were investigated for the first time by 1H-NMR-based metabolomics combined with histopathological observation and biochemical detection. Histopathological sections showed a certain degree of hepatocyte edema and hepatic sinus congestion in the liver tissue of the rats in the drug-administered group. Serum biochemical indicators revealed a significant increase in ALT, AST, and MDA, and a significant decrease in SOD. Metabolomic results showed that the metabolites in rats were changed after gavage administration of extracts from SHCW. By multivariate statistical analysis and univariate analysis, it was found that SHCW could cause the disorder of energy metabolism, oxidative stress and amino acid metabolism in rats, leading to liver damage. This comprehensive metabolomics approach demonstrates its ability to describe the global metabolic state of an organism and provides a powerful and viable tool for exploring drug-induced toxicity or side effects.

Alterations in protein and amino acid metabolism in rats fed a branched-chain amino acid- or leucine-enriched diet during postprandial and postabsorptive states.

BackgroundMany people believe in favourable effects of branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), especially leucine, on muscle protein balance and consume BCAAs for many years. We determined the effects of the chronic intake of a BCAA- or leucine-enriched diet on protein and amino acid metabolism in fed and postabsorptive states.MethodsRats were fed a standard diet, a diet with a high content of valine, leucine, and isoleucine (HVLID), or a high content of leucine (HLD) for 2 months. Half of the animals in each group were sacrificed in the fed state on the last day, and the other half were sacrificed after overnight fast. Protein synthesis was assessed using the flooding dose method (L-[3,4,5-3H]phenylalanine), proteolysis on the basis of chymotrypsin-like activity (CHTLA) of proteasome and cathepsin B and L activities.ResultsChronic intake of HVLID or HLD enhanced plasma levels of urea, alanine and glutamine. HVLID also increased levels of all three BCAA and branched-chain keto acids (BCKA), HLD increased leucine, ketoisocaproate and alanine aminotransferase and decreased valine, ketovaline, isoleucine, ketoisoleucine, and LDL cholesterol. Tissue weight and protein content were lower in extensor digitorum longus muscles in the HLD group and higher in kidneys in the HVLID and HLD groups. Muscle protein synthesis in postprandial state was higher in the HVLID group, and CHTLA was lower in muscles of the HVLID and HLD groups compared to controls. Overnight starvation enhanced alanine aminotransferase activity in muscles, and decreased protein synthesis in gastrocnemius (in HVLID group) and extensor digitorum longus (in HLD group) muscles more than in controls. Effect of HVLID and HLD on CHTLA in muscles in postabsorptive state was insignificant.ConclusionsThe results failed to demonstrate positive effects of the chronic consumption of a BCAA-enriched diet on protein balance in skeletal muscle and indicate rather negative effects from a leucine-enriched diet. The primary effects of both diets are an activated catabolism of BCAAs, which leads to an enhanced production of BCKA, alanine and glutamine and their utilization in visceral tissues and an impaired protein synthesis in postabsorptive state, particularly in fast-twitch (white) muscles.

Serum metabolomics reveals that arsenic exposure disrupted lipid and amino acid metabolism in rats: a step forward in understanding chronic arsenic toxicity.

Chronic arsenic exposure through drinking water threatens public health worldwide. Although its multiorgan toxicity has been reported, the impact of chronic arsenic exposure on the metabolic network remains obscure. In this study, male Sprague Dawley rats were exposed to 0.5, 2 or 10 ppm sodium arsenite for three months. An ultra-high performance liquid chromatography/mass spectrometry based metabolomics approach was utilized to unveil the global metabolic response to chronic arsenic exposure in rats. Distinct serum metabolome profiles were found to be associated with the doses. Eighteen differential metabolites were identified, and most of them showed dose-dependent responses to arsenic exposure. Metabolic abnormalities mainly involved lipid metabolism and amino acid metabolism. The metabolic alterations were further confirmed by hepatic gene expression. Expressions of cpt2, lcat, cact, crot and mtr were significantly elevated in high dose groups. This study provides novel evidence to support the association between arsenic exposure and metabolic disruption, and it contributes to understanding the mechanism of chronic arsenic toxicity.

Metabolomic analysis of amino acid and energy metabolism in rats supplemented with chlorogenic acid.

This study was conducted to investigate effects of chlorogenic acid (CGA) supplementation on serum and hepatic metabolomes in rats. Rats received daily intragastric administration of either CGA (60mg/kg body weight) or distilled water (control) for 4weeks. Growth performance, serum biochemical profiles, and hepatic morphology were measured. Additionally, serum and liver tissue extracts were analyzed for metabolomes by high-resolution (1)H nuclear magnetic resonance-based metabolomics and multivariate statistics. CGA did not affect rat growth performance, serum biochemical profiles, or hepatic morphology. However, supplementation with CGA decreased serum concentrations of lactate, pyruvate, succinate, citrate, β-hydroxybutyrate and acetoacetate, while increasing serum concentrations of glycine and hepatic concentrations of glutathione. These results suggest that CGA supplementation results in perturbation of energy and amino acid metabolism in rats. We suggest that glycine and glutathione in serum may be useful biomarkers for biological properties of CGA on nitrogen metabolism in vivo.

Effects and mechanisms of acetyl-L-cysteine in rats with chronic mountain sickness with H1-NMR metabolomics methods.

BackgroundWe established a rat model of chronic mountain sickness using acetyl-L-cysteine. Then we studied the effects and mechanisms of acetyl-L-cysteine (Da) in rats with chronic mountain sickness using nuclear magnetic resonance (H1-NMR) metabolomics methods.Material/MethodsUsing NMR spectroscopy combined with pattern recognition and orthogonal partial least squares discriminant analysis, we analyzed the impact of Da on blood metabolism in rats with chronic mountain sickness by determining different metabolites and changes in metabolic network in the blood of rats with mountain sickness after the intragastric administration of different doses of Da suspension.ResultsIncreased levels of amino acids (valine, tyrosine, 1-methyl-histidine, leucine, phenylalanine, and methionine) were detected in the blood of rats in the chronic mountain sickness group, yet significantly decreased levels were detected in control rats. At the same time, β-glucose and α-glucose levels were markedly elevated in the blood of rats in the model group but decreased in the chronic mountain sickness group, which indicated a statistically significant difference compared with the chronic altitude sickness model group (P<0.05).ConclusionsDa has a significant impact on the metabolism of rats with chronic mountain sickness. Da may act on the disturbed glucose metabolism and amino acid metabolism in rats triggered by chronic mountain sickness, resulting in the treatment and prevention of this disease.

Effect of acute acidosis on protein and amino acid metabolism in rats

Background & aims: Metabolic acidosis is a common finding in critical illness. The aim of the present study was to evaluate acute acidosis as a signal that induces changes in protein metabolism. Methods: In the first study, Wistar rats were infused for 6 h with HCl or saline resulting in blood pH 7.30±0.03 and 7.46±0.02, respectively. The whole body protein metabolism was evaluated using l-[1- 14C]leucine. In the second study, soleus and extensor digitorum longus muscles from normal rats were incubated in medium, pH 7.4, 7.3 or 7.0. Protein metabolism was evaluated using l-[1- 14C]leucine and tyrosine release. Results: In the in vivo study we observed increased protein turnover–protein synthesis, proteolysis and leucine oxidation and more negative protein balance in rats with acidosis. There was no change in protein synthesis in gastrocnemius muscle. We observed an increase in plasma levels of most amino acids including branched-chain amino acids and a decrease in intracellular amino acid pool in skeletal muscle. In vitro decrease in pH of 0.1 had no effect on protein metabolism, decrease of 0.4 decreased protein turnover and leucine oxidation. Conclusion: Acute metabolic acidosis is a protein wasting condition. Direct effect of acidosis on skeletal muscle is under condition in vivo modified by neurohumoral regulations.

Characteristics of nitrogen metabolism in rats with thioacetamide-induced liver cirrhosis

Female Sprague–Dawley rats were given 0.03% thioacetamide (TAA) in their drinking water daily for 4 or 12 weeks, and were then given normal water for 4 weeks after the end of a 12-week TAA treatment to investigate amino acid metabolism. In the malnourished precirrhotic stage (stage 1) and the malnourished cirrhotic stage (stage 2), the aromatic amino acids (AAA), Glu, Asp, Orn, Arg and Cit increased, and the branched-chain amino acids (BCAA) decreased slightly. Because these changes normalized in the well-nourished cirrhotic stage (stage 3), they might have resulted from impairment of hepatocytes and malnutrition. The net uptake of BCAA into the liver increased in stage 2, but the AAA uptake did not exceed that in normal controls. Portal venous plasma AAA increased to the same level as arterial plasma AAA. These results suggest that the decrease in BCAA was partially due to liver uptake and that the increase in AAA was induced by reduction of liver uptake and overproduction in extrahepatic tissues. The liver contents of BCAA and AAA were unchanged in all stages, so were fully utilized in the impaired liver. The increases in Glu, Asp, Orn and Cit might have resulted from overproduction in the liver, because these contents of the liver increased in stage 2. In conclusion, the changes in amino acid metabolism in rats with cirrhosis induced by TAA closely resemble those seen in human liver cirrhosis.

Effect of various non-hepatotoxic compounds on urinary and liver taurine levels in rats.

Administration of compounds which alter protein synthesis or sulphur amino acid metabolism in rats results in changes in the excretion of urinary taurine. Treatment with diethylmaleate (DEM) or phorone, which will deplete glutathione (GSH), reduces taurine excretion, whereas treatment with buthionine sulphoximine (BSO), which will inhibit glutathione synthesis, increases taurine excretion. Treatment with cycloheximide, an inhibitor of protein synthesis, increases taurine excretion, whereas pretreatment with phenobarbital, which will increase protein synthesis, decreases taurine excretion. Administration of agents which damage organs other than the liver such as the kidney, heart and testes, does not increase urinary taurine.

Changes in brain ECF amino acids in rats with experimentally induced hyperammonemia.

Using microdialysis, we studied brain extracellular fluid (ECF) amino acid metabolism in rats with experimentally induced hyperammonemia and regional elevation of brain ECF ammonia levels. The total brain ECF amino acid level was increased by an elevation of the blood ammonia level. Hyperammonemia elevated brain ECF aromatic amino acids and reduced arterial blood branched chain amino acids. When rats with hyperammonemia were intravenously administered norleucine, the brain ECF norleucine level rose markedly, suggesting increased permeability of the blood-brain barrier. When rats with hyperammonemia were infused with a branched chain amino acid-rich preparation, the elevated brain ECF aromatic amino acids level was not suppressed. Following local intracerebral ammonia infusion, only glutamate levels showed a marked elevation. These results suggest that impairment of the blood-brain barrier related to hyperammonemia increases the inflow of low molecular weight substances including amino acids. Furthermore, the ammonia-induced increase of glutamate in the cerebral ECF suggests that high ammonia levels may increase the excitability of the brain. Thus, ammonia may serve as a key factor in the onset of hepatic encephalopathy.

Effect of exogenous cortisone on amino acid metabolism in rats

1. 1. The effect of exogenous cortisone on concentration of free amino acids in serum, skeletal muscle, kidney, small intestine and liver was studied. 2. 2. The amino acid pool in serum, skeletal muscle and small intestine decreased significantly. 3. 3. Glutamine synthesis increased significantly in skeletal muscle. 4. 4. Levels of branched amino acids increased in serum and small intestine. 5. 5. Levels of alanine increased in kidney and liver.

Hepatic Cysteine Dioxygenase Activity and Sulfur Amino Acid Metabolism in Rats: Possible Indicators in the Evaluation of Protein Quality

Experiments were carried out to examine the possibility that the sulfur amino acid metabolism of rats may be an indicator of the nutritional value of dietary protein. Rats were fed diets containing 8, 16 or 24% of gluten, soy protein or casein for 3 wk. Hepatic cysteine dioxygenase activity, hepatic concentration of glutathione, cysteine and taurine and urinary taurine were examined. In addition, the sulfur amino acid metabolism of rats fed these diets fortified with the appropriate first limiting amino acid for 7 d was also examined. High urinary taurine excretion was observed in the three gluten groups, whereas very low urinary taurine excretion was observed with up to 24% soy protein or up to 16% casein. The hepatic hepatic cysteine dioxygenase activities of the gluten diet groups were higher than those of corresponding soy protein or casein diet groups, except that of rats fed the 24% casein diet. The hepatic concentrations of both glutathione and cysteine in gluten diet groups were also higher than those of corresponding soy protein or casein diet groups, except 24% soy protein and 16 and 24% casein diet groups. In rats fed the casein or soy protein diets urinary taurine excretion and hepatic cysteine dioxygenase activity increased with increasing methionine supplementation, the first limiting amino acid. Conversely, in rats fed the gluten diet both urinary taurine excretion and hepatic cysteine dioxygenase activity decreased with increasing lysine supplementation, the first limiting amino acid. These findings suggest that urinary taurine excretion and hepatic cysteine dioxygenase activity may be useful as sensitive indicators of the nutritional value of dietary protein.

Effects of maternal phenylalanine or tyrosine hydroxylase inhibition on postnatal maturation of catecholamine and amino acid metabolism in rats.

AbstractEffects of the inhibition of maternal phenylalanine (Phe) or tyrosine (Tyr) hydroxylase on the postnatal maturation of catecholamine, thyroxine and amino acid metabolisms were examined in young rats. The intraperitoneal injections of 100 mg/kg p‐chlorophenylalanine three times during the second gestational week together with 0.2% Phe solution as drinking water produced marked reduction in birth weight, body weight gain, brain weight, cerebral Tyr hydroxylase activity, adrenal epinephrine, renal norepinephrine and free amino acids in plasma and brain as well as delayed maturation of thermoregulation in the offspring. In contrast, the administration of 100 mg/kg α‐methyl‐p‐tyrosine with 0.2% Tyr supplementation did not affect general growth, but only decreased cerebral Tyr hydroxylase and serum thyroxine level, while cerebral dopamine was increased. These results indicate that maternal Phe hydroxylase inhibition induces more severe growth failure including catecholamine and amino acid metabolism than Try hydroxylase inhibition in postnatal development.

Effect of portacaval shunt on sulfur amino acid metabolism in rats.

Male rats were subjected to portacaval shunts (PCS). Postoperative growth curves were similar between PCS and sham-operated control animals, with complete recovery of preoperative body weight occurring within 7 days. PCS rats had 30% smaller livers and 39% larger spleens at autopsy. Total liver levels of reduced glutathione were decreased by 38% in PCS rats. Sulfur amino acid metabolism was studied 6 wk after PCS by injection of L-[methyl-14C]- or L-[1-14C]methionine with 14CO2 collection or by similarly administering L-[35S]methionine or L-[35S] cysteine and measuring 24-h urinary 35SO4, [35S]taurine, and total 35S. There were no significant differences in 14CO2 production over an 8-h period between PCS and sham rats. PCS rats excreted 31% more 35SO4 and 25% more total 35S when injected with 0.9 mmol of [35S]methionine and excreted 38% less [35S]taurine than controls when injected with [35S]-cysteine. These results indicate altered sulfur amino acid metabolism in PCS rats, an animal model of portal-systemic shunting.

The effect of diazepam on the cerebral metabolic state in rats and its interaction with nitrous oxide.

It has previously been shown in rats that diazepam alone has no effect on the cerebral metabolic rate (CMRO2) but that it interacts with nitrous oxide to produce a 40 per cent reduction in the CMRO2 value. In the present study, the effect of sedative doses of diazepam on the cerebral energy state, glycolysis, citric acid cycle, and amino acid metabolism in rats was determined in the presence and absence of a simultaneous administration of 70 per cent nitrous oxide, 45 s to 30 min after the diazepam injection. The metabolic response was very similar in the two groups despite the differences in metabolic rates of oxygen consumption. There were no changes in the cortical concentrations in ATP, ADP, AMP, phosphocreatine and creatine. The brain glycogen concentration was elevated during diazepam sedation, whereas brain glucose levels remained close to normal values except at 30 min after administration of diazepam alone, when the glucose level showed a 30 per cent increase. The onset of diazepam sedation was associated with an inhibition of glycolysis at the phosphofructokinase step in both groups. The reduced pyruvate concentration subsequently leads to a reduction in the pool size of the citric acid cycle intermediates. The concentrations of alanine and glutamate decreased during the period of diazepam sedation, while those of aspartate and glutamine increased. GABA and ammonia concentrations remained unchanged. Based on the cerebral metabolic response, the onset of diazepam sedation appears to be associated with an inhibition of rate of metabolism (glycolysis), both in the presence and absence of nitrous oxide. In that respect, diazepam has a metabolic profile similar to barbiturates.

[Effect of rhubarb (Rhei rhizoma) extract on urea nitrogen and amino acid metabolism after administration (author's transl)].

The effect of intraperitoneal administration of rhubarb extract (5 mg/rat) on urea nitrogen and amino acid metabolism in rats was investigated. Urea nitrogen concetrations were decreased by 21% in the liver at 8 hr and by 46-51% in the kidney at 4-8 hr after treatment. The excretion of urea and ammonia in the urine was not different from the control values and ammonia nitrogen concentrations in peripheral blood, the portal vein, liver and kidney were not different. On the other hand, in rats treated with rhubarb extract, α-amino acid nitrogen concentration in serum was significantly decreased by 20-36% at 2-8 hr. Seven amino acid concentrations in the plasma were decreased Gln (31%), Ala (51%), Gly (29%), Ser (26%), Glu (31%), Met (39%), and Arg (25%) and 3 amino acid concentrations in the liver were significantly decreased Gln (31%), Glu (42%), and Asp (45%) at 2 hr after the treatment. With respect to the net balance of plasma amino acids across various organs at 2 hr after the administration, release of Gln from the liver was decreased by 40% and the uptake of Gln by non-hepatic visceral organs was decreased by 44%.

Effect of 6-hydroxydopamine on brain and blood catecholamine, ammonia, and amino acid metabolism in rats subjected to high pressure oxygen induced convulsions.

Effects of 6-hydroxydopamine (6-OHDA) on rat brain and blood adrenaline (A), noradrenaline (NA), ammonia (NH3), gamma-aminobutyric acid (GABA), and amino acid metabolism prior to and after high pressure oxygen (OHP) induced convulsions have been studied. 6-OHDA reduces GABA and glutamate (Glu) rior to OHP exposure in rat brain so that the concentration is even equal to that seen in nondrugged animals after convulsion. Concomitantly, 6-OHDA reduces the latency of OHP-induced convulsion significantly, and increases brain NH3, glutamine, and asparagine significantly. Although 6-OHDA, in increasing dosage, elevates blood A concentration, convulsion produces a significant further increase in A. Blood NA was not significantly changed in drugged, convulsed animals and was much less than blood NA concentrations in nondrugged convulsed animals. Increasing doses of 6-OHDA also increase NH3 in the blood significantly and convulsion increases its concentration further. Latency of convulsion seems to be related to certain monoamine levels since in some drugged animals where A and total catecholamines are still reduced 96 h after the first of two doses of 6-OHDA, NA concentrations are recovered to relatively normal and the convulsion latency time is also increased although it remains significantly abbreviated from undrugged animals' convulsion time. Low brain GABA levels seem to be a prime effector of convulsive activity.