Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Enhanced oxidative stress and impairments in nitric oxide synthesis and bioavailability are of considerable importance in the pathogenesis of diabetic vascular diseases. The aim of the present work was to evaluate the metabolic effects of pharmacological doses of the melatonin, a known antioxidant, on streptozotocin-induced diabetic damage in rats. We investigated the indolamine's influence on the cellular redox-balance, nitric oxide (NO) level, and the activities of antioxidative defence enzymes, as well as the activities of enzymes involved in phase II detoxication and NADPH-generating pentose phosphate pathway. Blood glucose, glycated hemoglobin, bilirubin, as well as plasma alanine aminotransferase activities increased and body weight was reduced in rats with streptozotocin-induced (60 mg/kg, i.p.) diabetes (25 days). The NO level was markedly increased in diabetic plasma (by 50%) and aortic tissue (by 30%). The hyperglycemia resulted in reduced activities of glutathione peroxidase (by 25%), catalase (by 20%), glucose-6-phosphate dehydrogenase (by 55%) and transketolase (by 40%) in liver tissue of diabetic animals. Melatonin treatment (10 mg/kg, 18 days) did not influence the level of hyperglycemia or glycated hemoglobin and it had little effect on the activities of antioxidative enzymes. However, melatonin markedly reversed the activities of glucose-6-phosphate dehydrogenase and transketolase in liver tissue of diabetic rats. The most pronounced effect of the melatonin administration was the prevention of an increase in nitric oxide levels in blood plasma and aortic tissue during diabetes. In in vitro experiments, nitrosomelatonin formation in the presence of nitrosodonors was observed. This implies that melatonin might operate as an NO scavenger and carrier. Thus, melatonin treatment may have some beneficial effects in controlling diabetic vascular complications.
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PMID:Melatonin attenuates metabolic disorders due to streptozotocin-induced diabetes in rats. 1759 2

D-Galactosamine (GalN) depletes UTP primarily in liver, resulting in decreased RNA synthesis in hepatocytes. When given together with a sublethal dose of lipopolysaccharide (LPS), GalN highly sensitizes animals to produce apoptotic liver injury with severe hepatic congestion, resulting in rapid death. Melatonin is a cytokine modulator, antioxidant and anti-apoptotic agent. In the present study, we investigated the effect of melatonin on LPS-induced apoptotic liver damage in GalN-sensitized mice. Female CD-1 mice were intraperitoneally (i.p.) injected with melatonin (5.0mg/kg) 30min before GalN/LPS (700mg10microg/kg, i.p.), another two doses of melatonin (2.5mg/kg, i.p.) being administered 1 and 2h after GalN/LPS. Results showed that serum alanine aminotransferase (ALT) activities were markedly increased 8h after GalN/LPS treatment, massive hemorrhage being observed in histological sections of liver from GalN/LPS-treated mice. Melatonin significantly attenuated GalN/LPS-induced elevation of serum ALT. In parallel, melatonin distinctly improved GalN/LPS-induced congestion. Additional experiment showed that melatonin significantly attenuated GalN/LPS-induced hepatic apoptosis, measured by inhibition of caspase-3 activities and attenuation of DNA laddering. Furthermore, melatonin markedly increased hepatic Se-dependent glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd) activities and attenuated hepatic glutathione (GSH) depletion in GalN/LPS-treated mice. Increases in serum tumor necrosis factor alpha (TNF-alpha), which were observed in GalN/LPS-treated mice, were significantly reduced by melatonin. However, melatonin had no effect on LPS-evoked nitric oxide production in GalN-sensitized mice. Taken together, these results indicate that melatonin protected against LPS-induced liver damage in GalN-sensitized mice through its strong ROS-scavenging, antiinflammatory and antiapoptotic effects.
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PMID:Melatonin attenuates lipopolysaccharide (LPS)-induced apoptotic liver damage in D-galactosamine-sensitized mice. 1760 19

N-nitrosodiethylamine (NDEA) is a potent carcinogenic agent that induces liver cancer. To evaluate the chemopreventive function of melatonin in this experimental model, Wistar male rats received a single i.p. injection of NDEA or vehicle followed by weekly s.c. injections of carbon tetrachloride or vehicle for 6 weeks. Melatonin (5 mg/kg body weight) or its vehicle (0.5 mL saline) was given i.p. on a daily basis 2 hr before lights off for 20 wk. At the end of this period the rats were killed and liver and blood samples were taken for histological and biochemical studies. As markers for liver function, the activity of aspartate transaminase (AST) and alanine transaminase (ALT) and the levels of alpha-fetoprotein were measured in serum. To assess lipid peroxidation and the antioxidant status in liver and blood, the levels of thiobarbituric acid reactive substances (TBARS) and of reduced glutathione (GSH) were measured. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) was assessed in liver and erythrocyte fraction of NDEA-treated rats. NDEA administration inhibited body weight, macro- and microscopically detectable liver tumors and increased levels of plasma AST, ALT and alpha-fetoprotein. NDEA treatment decreased liver TBARS levels and CAT and SOD activities and increased liver GSH levels and GST and GPx activities. Plasma TBARS were augmented, while plasma GSH levels and the activities of erythrocyte CAT, SOD, GST and GPx decreased, in NDEA-treated rats. Melatonin administration significantly curtailed tumor development and counteracted all the biochemical effects.
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PMID:Prevention by melatonin of hepatocarcinogenesis in rats injected with N-nitrosodiethylamine. 1780 29

The production of reactive oxygen species during hepatic ischemia/reperfusion (I/R) can help create disturbances in microcirculation. This study examined the effect of melatonin, a pineal secretory product and a potent antioxidant, on the expression of vascular stress genes during hepatic I/R. Rats were subjected to 60 min of hepatic warm ischemia followed by 5 h reperfusion. Melatonin (10 mg/kg) was administered intraperitoneally 15 min before ischemia and immediately before reperfusion. The serum alanine aminotransferase and hepatic malondialdehyde levels increased markedly after I/R. These increases were significantly inhibited by melatonin. The levels of endothelin-1 (ET-1) and its receptor, ET(B) mRNA, were elevated by I/R but attenuated by melatonin. The mRNA levels of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and heme oxygenase-1 were significantly higher after I/ R. Melatonin augmented the increase in the eNOS mRNA level, whereas it reduced the increase in the iNOS mRNA level. The expression of tumor necrosis factor-alpha was increased markedly by I/R. This increase was also attenuated by melatonin. These results suggest that melatonin ameliorates the imbalanced expression of the vascular stress genes during hepatic I/R through its antioxidant property.
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PMID:Effect of melatonin on altered expression of vasoregulatory genes during hepatic ischemia/reperfusion. 1825 50

To compare the effects of alpha-ketoglutarate (alpha-KG) and melatonin on 24-h rhythmicity of oxidative stress in N-nitrosodiethylamine (NDEA)-injected Wistar male rats, melatonin (5 mg/kg i.p.) or alpha-KG (2 g/kg through an intragastric tube) was given daily for 20 weeks. In blood collected at 6 time points during a 24-h period, serum activity of aspartate transaminase (AST) and alanine transaminase (ALT) and the levels of alpha-fetoprotein (alpha-FP) were measured as markers of liver function. To assess lipid peroxidation and the antioxidant status, plasma levels of thiobarbituric acid reactive substances (TBARS) and of reduced glutathione (GSH) were measured, together with the activity of erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST). NDEA augmented mesor and amplitude of rhythms in AST and ALT activity and plasma alpha-FP levels and mesor values of plasma TBARS, while decreasing mesor values of plasma GSH and erythrocyte SOD, CAT, GPx and GST. Acrophases were delayed by NDEA in all cases except for alpha-FP rhythm, which became phase-advanced. Co-administration of melatonin or alpha-KG partially counteracted the effects of NDEA. Melatonin decreased mesor of plasma TBARS and augmented mesor of SOD activity. The results indicate that melatonin and alpha-KG are effective in protecting from NDEA-induced perturbation of 24-h rhythms in oxidative stress. Melatonin augmented antioxidant defense in rats.
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PMID:24-hour rhythms in oxidative stress during hepatocarcinogenesis in rats: effect of melatonin or alpha-ketoglutarate. 1833 50

Oxidative stress may have a role in liver damage after acute renal injury due to various reasons such as ischemia reperfusion (IR). Diabetes mellitus (DM) is an important disease for kidneys and may cause nephropathy as a long term complication. The aim of this study was to investigate protective effect of melatonin, a potent antioxidant, against distant organ injury on liver induced by renal IR in rats with or without DM. The rats were divided into six groups: control (n=7), DM (n=5), IR (n=7), DM+IR (n=7), melatonin+IR (Mel+IR) (melatonin, 4 mg/ kg during 15 days) (n=7), and Mel+DM+IR groups (n=7). Diabetes developed 3 days after single i.p. dose of 45 mg/kg streptozotocin. After 15 day, the left renal artery was occluded for 30 min followed 24 h of reperfusion in IR performed groups. DM did not alter oxidative parameters alone in liver tissue. The levels of malondialdehyde, protein carbonyl and nitric oxide with activities of xanthine oxidase and myeloperoxidase were increased in liver tissues of diabetic and non-diabetic IR groups. Nitric oxide level in DM was higher than control. The activities of catalase and superoxide dismutase were increased in IR groups in comparison with control and DM. ALT and AST levels were higher in IR and DM+IR groups than control and DM. Melatonin treatment reversed all these oxidant and antioxidant parameters to control values as well as serum liver enzymes. We concluded that renal IR may affect distant organs such as liver and oxidative stress may play role on this injury, but DM has not an effect on kidney induced distant organ injury via oxidant stress. Also, it was concluded that melatonin treatment may prevent liver oxidant stress induced by distant injury of kidney IR.
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PMID:Melatonin treatment against remote organ injury induced by renal ischemia reperfusion injury in diabetes mellitus. 1856 51

Burns cause thermal injury to local tissue, trigger systemic inflammatory processes and activate lipid peroxidation, leading to multiple distant organ injury. Melatonin is a lipid- and water-soluble antioxidant and membrane stabilizer with antiinflammatory, hepatoprotective and gastroptotective properties, among others. We studied the influence of melatonin on hepatic damage induced by thermal skin injury and its possible relation to hepatic lipid peroxidative status and systemic inflammatory response. Under ether anesthesia the shaved dorsum of rats was exposed to a 90 degrees C bath for 10 s. Melatonin was administered intraperitoneally immediately after burns. Malondialdehyde (MDA), aspartate transaminase (AST) and alanine transaminase (ALT) were determined in liver and blood plasma and used as markers of oxidative status. Plasma C-reactive protein (CRP) was used as a marker of systemic inflammatory response. Thermal skin injury caused significant elevation of hepatic MDA by 48%, plasma CRP levels by 30% and plasma AST and ALT activities by 2- and 3.5-fold, respectively, in comparison with normal control rats. Treatment with melatonin (10 mg/kg) significantly inhibited the elevation in hepatic MDA and plasma CRP levels, reaching control values at 24 h. Melatonin treatment restricts the elevation of plasma AST and ALT activities (P < 0.001), which remain significantly increased as compared with controls. In conclusion, the protective effect of melatonin is likely to be due to attenuated lipid peroxidation and interference with reduced oxidative stress and inflammatory response, as evidenced by decreased hepatic MDA and plasma CRP levels.
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PMID:Protective effect of melatonin against oxidative hepatic injury after experimental thermal trauma. 1935 93

Identifying and treating kidney injury in cirrhosis is important. Bile duct ligation (BDL) is a commonly used cholestatic liver disease model. We hypothesized that asymmetric dimethylarginine (ADMA) is involved in BDL-induced oxidative stress and kidney injury, which can be prevented by melatonin. We also intended to elucidate whether increased ADMA is due to increased protein arginine methyltransferase-1 (PRMT1, ADMA-synthesizing enzyme) and/or decreased dimethylarginine dimethylaminohydrolase (DDAH, ADMA-metabolizing enzyme). Three groups of young rats were studied, sham (N = 7), untreated BDL rats (N = 9), and melatonin-treated BDL rats (N = 6, BDL + M). Melatonin-treated BDL rats received daily melatonin 1 mg/kg/day via intraperitoneal injection. One-third of the young BDL rats died compared with none in the BDL + M group. All surviving rats were killed 14 days after surgery. BDL rats had higher plasma aspartate aminotransferase, alanine aminotransferase, direct and total bilirubin, and ammonia levels than shams. They also had kidney injury characterized by increased tubulointerstitial injury scores and plasma creatinine and symmetric dimethylarginine levels, which melatonin prevented. Plasma ADMA levels were elevated in BDL rats, combined with increased hepatic PRMT1 and decreased renal DDAH activity. In addition, melatonin increased hepatic DDAH2 expression, increased DDAH activity and concomitantly decreased ADMA contents in both the liver and kidney. In conclusion, melatonin therapy decreased mortality and prevented kidney injury induced by BDL via reduction of ADMA (by increasing DDAH activity) and oxidative stress.
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PMID:Melatonin prevents increased asymmetric dimethylarginine in young rats with bile duct ligation. 2021 Aug 51

Duchenne muscular dystrophy (DMD), a lethal disorder characterized by dystrophin absence, courses with chronic inflammation, sarcolemmal damage, and skeletal muscle degeneration. Among the multiple pathogenic mechanisms proposed for DMD, oxidative stress and inflammation are directly involved in the dystrophic process. Unfortunately, there is no current treatment for DMD, and the inflammatory process is an important target for therapies. Based on the antioxidant and anti-inflammatory properties of melatonin, we investigated whether melatonin treatment may reduce the dystrophic process. Ten DMD patients aged 12.8 +/- 0.98 yr, were treated with melatonin (60 mg at 21:00 hr plus 10 mg at 09:00 hr), and plasma levels of lipid peroxidation (LPO), nitrites (NO(x)), interleukin (IL)-1beta, IL-2, IL-6, tumor necrosis factor-alpha, interferon-gamma, and plasma markers of muscle injury, were determined at 3, 6 and 9 months of treatment. Healthy age- and sex-matched subjects were used as controls. The results show a significant increase in LPO, NO(x), and cytokine levels in plasma of DMD patients compared with controls. Melatonin administration reduced these values to control levels at 3 months of treatment, decreasing further 9 months later. In parallel, melatonin also reduced plasma levels of creatine kinase (CK; 50%), lactate dehydrogenase (28%), aspartate aminotransferase (28%), alanine aminotransferase (20%), and myoglobin (13%). These findings strongly support the conclusion that melatonin administration significantly reduced the hyperoxidative and inflammatory process in DMD patients, reducing the muscle degenerative process.
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PMID:Melatonin treatment normalizes plasma pro-inflammatory cytokines and nitrosative/oxidative stress in patients suffering from Duchenne muscular dystrophy. 2021 Aug 54

We aimed to determine the effect NAC (N-acetylcysteine) and melatonin on the histopathological and biochemical paramethers in the rats poisoned with CO (Carbon monoxide) experimentally. Winster albino female rats were placed in a plexiglass chamber and they were poisoned with CO. After the poisoning, rats were randomly divided into 3 groups. The group given only normal saline, was used as a control group (n = 9). The second group was given 30 mg/kg intraperitonally NAC (n = 10). And the third group was treated with 10 mg/kg of melatonin intramuscularly (n = 9). It is determined that some biochemical values affected by NAC but not by melatonin. CK, ALT, Lactate, MDA levels were significantly higher in NAC group than control and Melatonin group (p < 0.01 for all comparisons). Thiol level was lower in NAC group than control group and Melatonin group (p < 0.01 and p < 0.001, respectively). There were no statistical significant differences between the melatonin and control group. There were statistically significant difference between control, NAC and Melatonin groups according to brain and lung tissue damage. It is shown that both NAC and Melatonin are reducing the brain and lung tissue damage of CO poisoning but due to biochemical results worsened by NAC, Melatonin may recommend for CO poisoning (Tab. 3, Ref. 21).
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PMID:The effect of antioxidants (N-acetylcysteine and melatonin) on hypoxia due to carbonmonoxide poisoning. 2058 44


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