Taurine Ameliorates Thyroid Hypofunction and Renal Injury in L-NAME-Induced Hypertensive Rats

Drug Research ◽  
2018 ◽  
Vol 69 (02) ◽  
pp. 83-92 ◽  
Author(s):  
Isaac Adedara ◽  
Sanmi Alake ◽  
Laide Olajide ◽  
Mercy Adeyemo ◽  
Temitayo Ajibade ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Thyroid Stimulating Hormone ◽  
Antioxidant Enzyme Activities ◽  
Myeloperoxidase Activity ◽  
Hypertensive Rats ◽  
Nitric Oxide Synthase Inhibitor ◽  
Reference Drug ◽  
Male Wistar Rats ◽  
Synthase Inhibitor

AbstractThere is a growing global interest in hypertension due to its associated complications including renal dysfunction in patients. The thyroid system reportedly regulates renal function in both animal and human. The present study investigated the therapeutic efficacy of taurine on renal and thyroid dysfunctions in hypertensive rats. Hypertension was induced by oral administration of nitric oxide synthase inhibitor, N-nitro L-arginine-methyl-ester (L-NAME), at 40 mg/kg body weight to the male Wistar rats for 14 consecutive days. The hypertensive rats were subsequently treated with either taurine (100 and 200 mg/kg) or reference drug atenolol (10 mg/kg) for another 14 consecutive days. Hypertensive rats showed renal damage evidenced by elevated plasma creatinine and urea levels when compared with normotensive control rats. Furthermore, L-NAME-induced hypertensive rats showed decreased circulatory concentrations of thyroid stimulating hormone, thyroxine, triiodothyronine and the ratio of triiodothyronine to thyroxine. The marked decrease in the renal antioxidant enzyme activities and nitric oxide level was accompanied by significant increase in myeloperoxidase activity and biomarkers of oxidative stress in hypertensive rats. Histological examination of kidneys from hypertensive rats revealed congestion of blood vessels, hemorrhagic lesion and disorganized glomerular structure. However, treatment with taurine or atenolol significantly reversed the suppression of thyroid function, ameliorated renal oxidative stress and histopathological lesions in L-NAME-induced hypertensive rats. Taurine may be a useful chemotherapeutic supplement in enhancing renal and thyroid functions in hypertensive patients.

Aminoguanidine, an inducible nitric oxide synthase inhibitor, plus N-acetylcysteine treatment reduce the lipopolysaccharideaugmented hepatotoxicity in rats with cirrhosis

2002 ◽  
Vol 21 (7) ◽  
pp. 359-364 ◽  
Author(s):  
S Dogru-Abbasoglu ◽  
J Balkan ◽  
Ö Kanbaglõ ◽  
U Cevikbas ◽  
G Aykac-Toker ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Tap Water ◽  
Nitric Oxide Synthase Inhibitor ◽  
Inos Inhibitor ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Hepatic cirrhosis is produced in rats by administration of thioacetamide (TAA) (0.3 g/L tap water for a period of three months). This treatment caused an increase in oxidative stress in the liver. Lipopolysaccharide (LPS) administration (5 mg/kg) to rats with cirrhosis was observed to increase hepatotoxicity as well as oxidative stress according to biochemical and histopathological findings. However, aminoguanidine (AG), an inducible nitric oxide synthase (iNOS) inhibitor, plus N-acetylcysteine (NAC) treatment reduced the LPS-augmented hepatotoxicity in rats with cirrhosis without making any changes in oxidative stress in the liver.

scholarly journals Tetramethoxystilbene-Loaded Liposomes Restore Reactive-Oxygen-Species-Mediated Attenuation of Dilator Responses in Rat Aortic Vessels Ex vivo

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4360 ◽  
Author(s):  
Azziza Zaabalawi ◽  
Cai Astley ◽  
Lewis Renshall ◽  
Frances Beards ◽  
Adam P. Lightfoot ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nadph Oxidase ◽  
Ex Vivo ◽  
Antioxidant Properties ◽  
Young Male ◽  
Oxidase Inhibitor ◽  
Nitric Oxide Synthase Inhibitor ◽  
Male Wistar Rats ◽  
Synthase Inhibitor ◽  
Oxide Synthase

The methylated analogue of the polyphenol resveratrol (RV), 2,3′,4,5′-tetramethoxystilbene (TMS) displays potent antioxidant properties and is an effective cytochrome P450 (CYP) 1B1 inhibitor. The bioavailability of TMS is low. Therefore, the use of liposomes for the encapsulation of TMS is a promising delivery modality for enhanced uptake into tissues. We examined the effect of delivery of TMS in liposomes on the restoration of vasodilator responses of isolated aortic vessels after acute tension elevation ex vivo. Aortic vessels from young male Wistar rats were isolated, and endothelial-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) responses assessed. Acute tension elevation (1 h) significantly reduced ACh dilator responses, which were restored following incubation with superoxide dismutase or apocynin (an NADPH oxidase inhibitor). Incubation with TMS-loaded liposomes (mean diameter 157 ± 6 nm; PDI 0.097) significantly improved the attenuated dilator responses following tension elevation, which was sustained over a longer period (4 h) when compared to TMS solution. Endothelial denudation or co-incubation with L-NNA (Nω-nitro-l-arginine; nitric oxide synthase inhibitor) resulted in loss of dilator function. Our findings suggest that TMS-loaded liposomes can restore attenuated endothelial-dependent dilator responses induced by an oxidative environment by reducing NADPH-oxidase-derived ROS and potentiating the release of the vasodilator nitric oxide. TMS-loaded liposomes may be a promising therapeutic strategy to restore vasodilator function in vascular disease.

Release of glutathione from erythrocytes and other markers of oxidative stress in carbon monoxide poisoning

1997 ◽  
Vol 82 (5) ◽  
pp. 1424-1432 ◽  
Author(s):  
Stephen R. Thom ◽  
Melissa Kang ◽  
Donald Fisher ◽  
Harry Ischiropoulos
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Carbon Monoxide Poisoning ◽  
Thiobarbituric Acid ◽  
Nitric Oxide Synthase Inhibitor ◽  
Oxidized Proteins ◽  
Markers Of Oxidative Stress ◽  
Synthase Inhibitor

Thom, Stephen R., Melissa Kang, Donald Fisher, and Harry Ischiropoulos. Release of glutathione from erythrocytes and other markers of oxidative stress in carbon monoxide poisoning. J. Appl. Physiol. 82(5): 1424–1432, 1997.—Rats exposed to CO in a manner known to cause oxidative stress in brain exhibited a twofold increase in plasma levels of oxidized proteins, thiobarbituric acid-reactive substances (TBARS), oxidized glutathione (GSSG), and reduced glutathione (GSH). Changes were neither directly related to hypoxic stress from carboxyhemoglobin nor significantly influenced by circulating platelets or neutrophils. Treatment with the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester inhibited elevations in GSH and GSSG but not changes in oxidized proteins or TBARS, suggesting that two oxidative mechanisms may be operating in this model and that GSH and GSSG elevations involved nitric oxide-derived oxidants. Elevations of blood GSH and GSSG occurred at different anatomic sites, indicating that no single organ was the source of the increased peptides. Animals that underwent exchange transfusion with a hemoglobin-containing saline solution did not exhibit elevations in GSH and GSSG, suggesting that blood-borne cells released these peptides in response to oxidative stress. In in vitro studies, erythrocytes, but not platelets and leukocytes, responded to oxidative stress from peroxynitrite by releasing GSH, whereas no release was observed in response to nitric oxide or superoxide. Glucose, maltose, and cytochalasin B, agents that protect extracellular components of the hexose transport protein complex from oxidative stress, prevented GSH release. The data indicate that nitric oxide-derived oxidants are involved in CO-mediated oxidative stress within the vascular compartment and that elevations of several compounds may be useful for identifying exposures to CO likely to precipitate brain injury.

scholarly journals L-arginine, a nitric oxide precursor, reduces dapsone-induced methemoglobinemia in rats

2012 ◽  
Vol 48 (1) ◽  
pp. 87-94 ◽  
Author(s):  
Natália Valadares de Moraes ◽  
Mateus Machado Bergamaschi ◽  
Maria de Lourdes Pires Bianchi ◽  
Juliana Bordinassi Bragheto ◽  
Wilson Roberto Malfará ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Multiple Dose ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nitric Oxide Formation ◽  
Oxide Precursor ◽  
P450 Enzyme ◽  
Male Wistar Rats ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Dapsone use is frequently associated to hematological side effects such as methemoglobinemia and hemolytic anemia, which are related to N-hydroxylation mediated by the P450 enzyme system. The aim of the present study was to evaluate the influence of L-arginine supplementation, a precursor for the synthesis of nitric oxide, as single or multiple dose regimens on dapsone-induced methemoglobinemia. Male Wistar rats were treated with L-arginine at 5, 15, 30, 60 and 180 mg/kg doses (p.o., gavage) in single or multiple dose regimens 2 hours prior to dapsone administration (40 mg/kg, i.p.). The effect of the nitric oxide synthase inhibitor L-NAME was investigated by treatment with multiple doses of 30 mg/kg (p.o., gavage) 2 hours before dapsone administration. Blood samples were collected 2 hours after dapsone administration. Erythrocytic methemoglobin levels were assayed by spectrophotometry. The results showed that multiple dose supplementations with 5 and 15 mg/kg L-arginine reduced dapsone-induced methemoglobin levels. This effect is mediated by nitric oxide formation, since the reduction in methemoglobin levels by L-arginine is blocked by simultaneous administration with L-NAME, a nitric oxide synthase inhibitor.

scholarly journals Metabolic changes in pulmonary mitochondria of rats with experimental hyperhomocysteinemia

2017 ◽  
Vol 63 (3) ◽  
pp. 248-254 ◽  
Author(s):  
D.V. Medvedev ◽  
V.I. Zvyagina ◽  
O.M. Uryasev ◽  
E.S. Belskikh ◽  
S.V. Bulatetskiy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Mitochondrial Protein ◽  
Protein Carbonylation ◽  
Tissue Respiration ◽  
Mitochondrial Enzymes ◽  
Male Wistar Rats ◽  
Nitric Oxide Metabolites ◽  
Synthase Inhibitor ◽  
Lung Oxidative Stress

Hyperhomocysteinemia is a risk factor for many human diseases, including pulmonary pathologies. In this context much interest attracts secondary mitochondrial dysfunction, which is an important link in pathogenesis of diseases associated with hyperhomocysteinemia. The study was conducted using male Wistar rats. It was found that under conditions of severe hyperhomocysteinemia caused by administration of methionine, homocysteine was accumulated in lung mitochondria thus suggesting a direct toxic effect on these organelles. However, we have not observed any significant changes in the activity of mitochondrial enzymes involved in tissue respiration (succinate dehydrogenase) and oxidative phosphorylation (H+-ATPase) and of cytoplasmic lactate dehydrogenase. Also there was no accumulation of lactic acid in the cytoplasm. Animals with severe hyperhomocysteinemia had higher levels of lung mitochondrial protein carbonylation, decreased reserve-adaptive capacity, and increased superoxide dismutase activity. These results indicate that severe hyperhomocysteinemia causes development of oxidative stress in lung mitochondria, which is compensated by activation of antioxidant protection. These changes were accompanied by a decrease in the concentration of mitochondrial nitric oxide metabolites. Introduction to animals a nonselective NO-synthase inhibitor L-NAME caused similar enhancement of mitochondrial protein carbonylation. It demonstrates importance of reducing bioavailability of nitric oxide, which is an antioxidant in physiological concentrations, in the development of oxidative stress in lung mitochondria during hyperhomocysteinemia. Key words: hyperhomocysteinemia, nitric oxide, lung, oxidative stress, mitochondria

Hydrogen sulfide as a mediator of endothelium-dependent relaxation evoked by Moringa oleifera leaf extract in mesenteric arterial beds isolated from L-NAME hypertensive rats

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Direk Aekthammarat ◽  
Panot Tangsucharit ◽  
Patchareewan Pannangpetch
Keyword(s):  
Nitric Oxide ◽  
Moringa Oleifera ◽  
Channel Blocker ◽  
Resistance Arteries ◽  
Hypertensive Rats ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor ◽  
Gap Junctional ◽  
Oxide Synthase ◽  
Endothelium Dependent Relaxation

AbstractObjectivesAqueous extract of Moringa oleifera leaves (MOE) is a potent inducer of endothelium-dependent relaxation of mesenteric resistance arteries of rats induced to be hypertensive using Nω-nitro-L-arginine methyl ester (L-NAME). Hydrogen sulfide (H2S) has been shown to participate in endothelium-dependent relaxation of small resistance arteries. Therefore, this study aimed to investigate whether endothelial H2S-dependent signaling plays a role in the vasorelaxation in response to MOE.MethodsMesenteric arterial beds isolated from L-NAME hypertensive rats were set up in an ex vivo perfusion system for measurement of vasoreactivity. All experiments were performed in the presence of the nitric oxide synthase inhibitor, L-NAME (100 µM) and the cyclooxygenase inhibitor, indomethacin (10 µM) to prevent the formation of nitric oxide and prostanoids, respectively.ResultsIn the presence of the nitric oxide synthase inhibitor, L-NAME and the cyclooxygenase inhibitor, indomethacin, the endothelium-dependent vasorelaxation induced by MOE (0.001–3 mg) was completely inhibited by DL-propargylglycine (100 µM), which inhibits the H2Sgenerating enzyme, cystathionine γ-lyase. This H2Sdependent response was reduced by the KATP channel blocker; glibenclamide (10 µM), the KCa channel blocker; tetraethylammonium (1 µM), and the myo-endothelial gap-junctional uncoupler; 18α-glycyrrhetinic acid (10 µM). In contrast, the muscarinic receptor antagonist, atropine (100 µM), did not affect the response to MOE.ConclusionsThe results may suggest that H2S is the likely mediator of endothelium-dependent relaxation in response to MOE in mesenteric arterial beds of L-NAME-induced hypertensive rats. MOE-induced H2S-dependent vasorelaxation involves activation of KATP and KCa channels and requires myo-endothelial gap-junctional communication.

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