Modulation of arginine and asymmetric dimethylarginine concentrations in liver and plasma by exogenous hydrogen sulfide in LPS-induced endotoxemia

Plasma levels of asymmetric dimethylarginine (ADMA) are known to be elevated under pathological conditions, but reports on intracellular ADMA levels are scarce. In this study, we investigated whether lipopolysaccharide (LPS)-induced endotoxemia alters the intra-and extra-cellular partition of L-arginine and ADMA. The effect of H2S pretreatment was also researched. Wistar rats were given sodium hydrogen sulfide (NaHS, 1 mg.(kg body mass)(-1)) one hour before the LPS injections (20 mg.kg(-1)). Six hours after the LPS treatment, the animals were sacrificed. Myeloperoxidase (MPO) and dimethylarginine dimethylaminohydrolase (DDAH) activities and levels of hypoxia-inducible factor (HIF)-1 alpha were measured in the liver. ADMA and arginine levels were determined using HPLC. LPS injection caused liver injury, as evidenced by the activities of alanine transaminase, aspartate transaminase, and arginase. LPS increased L-arginine content and decreased DDAH activity in the rat liver. MPO activity and HIF-1 alpha levels indicated inflammation and hypoxia. Despite the accumulation of ADMA in the plasma, the level remained unchanged in the liver. NaHS pretreatment restored both the DDAH activity and intracellular L-arginine levels. It is concluded that increased H2S generation has a potency to restore hepatic L-arginine levels and ADMA handling in endotoxemia. Extra-and intra-cellular partitions of ADMA seem to depend on transport proteins as well as the DDAH activity

Effect of Carnosine on Prooxidant-Antioxidant Balance in Several Tissues of Rats Exposed to Chronic Cold Plus Immobilization Stress

In this study, we investigated the effect of L-carnosine (CAR) on prooxidant antioxidant balance in several tissues of rats exposed to chronic stress. Both cold and immobilization stresses were applied to rats at the same time. In the stress group, rats were placed in restraint cages and kept in a cold room (+4 degrees C) for I h for 21 days (5 days a week). Rats were injected with CAR (250 mg/kg, i.p.) at 30 min before stress application. Malondialdehyde, diene conjugate, protein carbonyl and nitrotyrosine levels, nonenzymatic (glutathione, vitamin E, and vitamin C), and enzymatic (catalase, superoxide dismutase and glutathione peroxidase) antioxidants were determined in the liver, heart, and brain tissues. Chronic cold plus immobilization stress was observed to affect especially the prooxidant antioxidant status in the brain tissue of rats. This is the first report showing the beneficial effects of CAR on oxidative stress in the brain in rats exposed to stress

Effect of Carnosine on Prooxidant^|^ndash;Antioxidant Balance in Several Tissues of Rats Exposed to Chronic Cold Plus Immobilization Stress

In this study, we investigated the effect of L-carnosine (CAR) on prooxidant antioxidant balance in several tissues of rats exposed to chronic stress. Both cold and immobilization stresses were applied to rats at the same time. In the stress group, rats were placed in restraint cages and kept in a cold room (+4 degrees C) for I h for 21 days (5 days a week). Rats were injected with CAR (250 mg/kg, i.p.) at 30 min before stress application. Malondialdehyde, diene conjugate, protein carbonyl and nitrotyrosine levels, nonenzymatic (glutathione, vitamin E, and vitamin C), and enzymatic (catalase, superoxide dismutase and glutathione peroxidase) antioxidants were determined in the liver, heart, and brain tissues. Chronic cold plus immobilization stress was observed to affect especially the prooxidant antioxidant status in the brain tissue of rats. This is the first report showing the beneficial effects of CAR on oxidative stress in the brain in rats exposed to stress

The protection by heme oxygenase-1 induction against thioacetamide-induced liver toxicity is associated with changes in arginine and asymmetric dimethylarginine

This study was designed to investigate the role of HO-1 induction in prevention of thioacetamide (TAA)-induced oxidative stress, inflammation and liver damage. The changes in hepatic dimethylarginine dimethylaminohydrolase (DDAH) activity as well as plasma arginine and asymmetric dimethylarginine (ADMA) levels were also measured to evaluate nitric oxide (NO) bioavailability. Rats were divided into four groups as control, hemin, TAA and hemin+TAA groups. Hemin (50mgkg1, i.p.) was injected to rats 18h before TAA treatment to induce HO-1 enzyme expression. Rats were given TAA (300mgkg1, i.p.) and killed 24h after treatment. Although TAA treatment produced severe hepatic injury, upregulation of HO-1 ameliorated TAA-induced liver damage up to some extent as evidence by decreased serum alanine transaminase, aspartate transaminase and arginase activities and histopathological findings. Induction of HO-1 stimulated antioxidant system and decreased lipid peroxidation in TAA-treated rats. Myeloperoxidase activity and inducible NO synthase protein expression were decreased, whereas DDAH activity was increased by hemin injection in TAA-treated rats. Induction of HO-1 was associated with increased arginine levels and decreased ADMA levels, being the main determinants of NO production, in plasma of TAA-treated rats. In conclusion, our results indicate that HO-1 induction alleviated increased oxidative stress and inflammatory reactions together with deterioration in NO production in TAA-induced liver damage in rats. Copyright (c) 2012 John Wiley & Sons, Ltd

Resveratrol improves high-fructose-induced vascular dysfunction in rats

High levels of fructose in the diet results in metabolic abnormalities and vascular disorders. In this study, the effect of resveratrol (RES) on vascular relaxation and contraction responses was examined in the aorta of high-fructose (HFr)-fed rats. mRNA expressions of aortic sirtuin 1 (SIRT1), GLUT5, and aldolase B were also investigated. Rats were given fructose (30%) and (or) RES (50 mg.L-1) in their drinking water for 8 weeks. In the HFr-fed rats, plasma levels of arginine and the ratio of arginine: asymmetric dimethylarginine (ADMA) decreased, whereas leptin levels increased. Decreased relaxation and increased contractile responses were detected in aortic rings. However, the aortic expressions of SIRT1, GLUT5, and aldolase B remained unchanged. RES treatment restored HFr-induced vascular dysfunction without improvements in insulin resistance. Treatment of HFr-fed rats with RES increased plasma levels of arginine and the L-arginine: ADMA ratio, and decreased plasma levels of leptin. RES increased SIRT1 expression, but decreased the expression of GLUT5 and aldolase B in aortas from HFr-fed rats. These results suggest that RES contributes to the restoration of HFr-induced vascular dysfunction in rats, at least in part, by up-regulation of SIRT 1 and down-regulation of GLUT5 and aldolase B in the aorta. Moreover, RES may have a positive influence on vasculature by partly restoring the plasma arginine: ADMA ratio and leptin levels

Polymorphisms of endothelin 1 (G5665T and T-1370G) and endothelin receptor type A (C+70G and G-231A) in Graves' disease

Purpose: Endothelin 1 (EDN1) is a strong angiogenic and mitogenic factor, playing a key role in hypervascularization, thyroid follicle cell hyperplasia, and lymphocyte infiltration in the thyroid gland of patients with Graves' disease (GD). EDN1 induces angiogenesis and mitogenesis via endothelin receptor type A (EDNRA). This study examined the possible association of EDN1 (G5665T and T-1370G) and EDNRA (C+ 70G and G-231A) single nucleotide polymorphisms (SNPs) with the occurrence of GD, and evaluates the relationship between genotypes and clinical/laboratory manifestations of GD

Effects of resveratrol on high-fructose-induced testis injury in rats

This study investigated whether a high-fructose (HFr) diet changes the morphology of seminiferous tubules (ST) in rats and resveratrol (RES) has a possible restoring effect in this sense. Fructose (30%; w/v) was administered to rats alone or together with RES (50 mg/L) in drinking water for 8 weeks. In the HFr group, destruction of the germinal epithelium led to the detection of immature germ cells in the lumen. HFr diet gave rise to a decrease in the ST diameters (p < 0.05), Johnsen's tubular biopsy score values (p < 0.001), and an increase in the apoptotic index (p < 0.05). Ultrastructurally, HFr feeding increased lipid accumulation (p < 0.01), mitochondrial damage, and acrosomal abnormalities in spermatogenic cells. Treatment of HFr-fed rats with RES improved the reduced ST diameters and overall general histological and ultrastructural abnormalities of the STs, but did not change the increased apoptotic index

Effects of resveratrol on high-fructose-induced testis injury in rats

This study investigated whether a high-fructose (HFr) diet changes the morphology of seminiferous tubules (ST) in rats and resveratrol (RES) has a possible restoring effect in this sense. Fructose (30%; w/v) was administered to rats alone or together with RES (50 mg/L) in drinking water for 8 weeks. In the HFr group, destruction of the germinal epithelium led to the detection of immature germ cells in the lumen. HFr diet gave rise to a decrease in the ST diameters (p < 0.05), Johnsen's tubular biopsy score values (p < 0.001), and an increase in the apoptotic index (p < 0.05). Ultrastructurally, HFr feeding increased lipid accumulation (p < 0.01), mitochondrial damage, and acrosomal abnormalities in spermatogenic cells. Treatment of HFr-fed rats with RES improved the reduced ST diameters and overall general histological and ultrastructural abnormalities of the STs, but did not change the increased apoptotic index