Renoprotective and antihypertensive effects of S-allylcysteine in 5/6 nephrectomized rats

2007 ◽  
Vol 293 (5) ◽  
pp. F1691-F1698 ◽  
Author(s):  
Cristino Cruz ◽  
Ricardo Correa-Rotter ◽  
Dolores Javier Sánchez-González ◽  
Rogelio Hernández-Pando ◽  
Perla D. Maldonado ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Inducible Nitric Oxide Synthase ◽  
Renal Damage ◽  
Nitrosative Stress ◽  
Antioxidant Properties ◽  
Oxidative And Nitrosative Stress ◽  
Nitric Oxide Synthase 3 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Progressive renal damage and hypertension are associated with oxidative and nitrosative stress. On the other hand, S-allylcysteine (SAC), the most abundant organosulfur compound in aged garlic extract (AG), has antioxidant properties. The effects of SAC and AG on blood pressure, renal damage, and oxidative and nitrosative stress were studied in five-sixths nephrectomized rats treated with SAC (200 mg/kg ip) and AG (1.2 ml/kg ip) every other day for 30 days. Proteinuria and serum creatinine and blood urea nitrogen concentrations were measured on days 0, 5, 10, 15, and 30, and systolic blood pressure was recorded on days 0, 15, and 30. The degree of glomerulosclerosis and tubulointerstitial damage, the immunostaining for inducible nitric oxide synthase, 3-nitrotyrosine, poly(ADP-ribose), and the subunits of NADPH oxidase p22phox and gp91phox, and the activity of SOD were determined on day 30. SAC and AG reduced hypertension, renal damage, and the abundance of inducible nitric oxide synthase, 3-nitrotyrosine, poly(ADP-ribose), p22phox, and gp91phox and increased SOD activity. Our data suggest that the antihypertensive and renoprotective effects of SAC and AG are associated with their antioxidant properties and that they may be used to ameliorate hypertension and delay the progression of renal damage.

Protective effect of orally administered carnosine on bleomycin-induced lung injury

2007 ◽  
Vol 292 (5) ◽  
pp. L1095-L1104 ◽  
Author(s):  
Salvatore Cuzzocrea ◽  
Tiziana Genovese ◽  
Marco Failla ◽  
Graziella Vecchio ◽  
Mary Fruciano ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Lung Injury ◽  
Inducible Nitric Oxide Synthase ◽  
Antioxidant Properties ◽  
Myeloperoxidase Activity ◽  
Intratracheal Administration ◽  
Cell Counts ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Carnosine is an endogenously synthesized dipeptide composed of β-alanine and l-histidine. It acts as a free radical scavenger and possesses antioxidant properties. Carnosine reduces proinflammatory and profibrotic cytokines such as transforming growth factor-β (TGF-β), IL-1, and TNF-α in different experimental settings. In the present study, we investigated the efficacy of carnosine on the animal model of bleomycin-induced lung injury. Mice were subjected to intratracheal administration of bleomycin and were assigned to receive carnosine daily by an oral bolus of 150 mg/kg. One week after fibrosis induction, bronchoalveolar lavage (BAL) cell counts and TGF-β levels, lung histology, and immunohistochemical analyses for myeloperoxidase, TGF-β, inducible nitric oxide synthase, nitrotyrosine, and poly(ADP-ribose) polymerase were performed. Finally, apoptosis was quantified by terminal deoxynucleotidyltransferase-mediated UTP end-labeling assay. After bleomycin administration, carnosine-treated mice exhibited a reduced degree of lung damage and inflammation compared with wild-type mice, as shown by the reduction of 1) body weight, 2) mortality rate, 3) lung infiltration by neutrophils (myeloperoxidase activity and BAL total and differential cell counts), 4) lung edema, 5) histological evidence of lung injury and collagen deposition, 6) lung myeloperoxidase, TGF-β, inducible nitric oxide synthase, nitrotyrosine, and poly(ADP-ribose) polymerase immunostaining, 7) BAL TGF-β levels, and 8) apoptosis. Our results indicate that orally administered carnosine is able to prevent bleomycin-induced lung injury likely through its direct antioxidant properties. Carnosine is already available for human use. It might prove useful as an add-on therapy for the treatment of fibrotic disorders of the lung where oxidative stress plays a role, such as for idiopathic pulmonary fibrosis, a disease that still represents a major challenge to medical treatment.

scholarly journals Myoglobin Protects the Heart from Inducible Nitric-oxide Synthase (iNOS)-mediated Nitrosative Stress

2003 ◽  
Vol 278 (24) ◽  
pp. 21761-21766 ◽  
Author(s):  
Axel Gödecke ◽  
Andre Molojavyi ◽  
Jacqueline Heger ◽  
Ulrich Flögel ◽  
Zhaoping Ding ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Nitrosative Stress ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Beneficial Effects of L-Canavanine, a Selective Inhibitor of Inducible Nitric Oxide Synthase, during Rodent Endotoxaemia

1996 ◽  
Vol 90 (5) ◽  
pp. 369-377 ◽  
Author(s):  
Lucas Liaudet ◽  
François Feihl ◽  
Anne Rosselet ◽  
Michèle Markert ◽  
Jean-Marc Hurni ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Methyl Ester ◽  
Nitric Oxide Synthase ◽  
Cardiac Index ◽  
Inducible Nitric Oxide Synthase ◽  
Selective Inhibitor ◽  
Constitutive Nitric Oxide Synthase ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

1. The cardiovascular failure in sepsis may result from increased nitric oxide biosynthesis, through the diffuse expression of an inducible nitric oxide synthase. In such conditions, nitric oxide synthase inhibitors might be of therapeutic value, but detrimental side effects have been reported with their use, possibly related to the blockade of constitutive nitric oxide synthase. Therefore, the use of selective inhibitors of inducible nitric oxide synthase might be more suitable. The aim of this study was to evaluate the effects of l-canavanine, a potentially selective inhibitor of inducible nitric oxide synthase, in an animal model of septic shock. 2. Anaesthetized rats were challenged with 10 mg/kg lipopolysaccharide intravenously. One hour later, they randomly received a 5 h infusion of either l-canavanine (20 mg h−1 kg−1, n = 15), nitro-l-arginine methyl ester (5 mgh−1 kg−1, n = 13) or 0.9% NaCl (2 ml h−1 kg−1, n = 21). Lipopolysaccharide induced a progressive fall in blood pressure and cardiac index, accompanied by a significant lactic acidosis and a marked rise in plasma nitrate. All these changes were significantly attenuated by l-canavanine, which also improved the tolerance of endotoxaemic animals to acute episodes of hypovolemia. In addition, l-canavanine significantly increased survival of mice challenged with a lethal dose of lipopolysaccharide. In contrast to l-canavanine, nitro-l-arginine methyl ester increased blood pressure at the expense of a severe fall in cardiac index, while largely enhancing lactic acidosis. This agent did not improve survival of endotoxaemic mice. In additional experiments, we found that the pressor effect of l-canavanine in advanced endotoxaemia (4 h) was reversed by l-arginine, confirming that it was related to nitric oxide synthase inhibition. In contrast, l-canavanine did not exert any influence on blood pressure in the very early stage (first hour) of endotoxaemia or in the absence of lipopolysaccharide exposure, indicating a lack of constitutive nitric oxide synthase inhibition by this agent. 3. In conclusion, l-canavanine produced beneficial haemodynamic and metabolic effects and improved survival in rodent endotoxic shock. The actions of l-canavanine were associated with a selective inhibition of inducible nitric oxide synthase and were in marked contrast to the deleterious consequences of nitro-l-arginine methyl ester, a non-selective nitric oxide synthase inhibitor, in similar conditions.

Modulation of oxidative–nitrosative stress and inflammatory response by rapamycin in target and distant organs in rats exposed to hindlimb ischemia–reperfusion: the role of mammalian target of rapamycin

2019 ◽  
Vol 97 (12) ◽  
pp. 1193-1203
Author(s):  
Zumrut Kocak ◽  
Meryem Temiz-Resitoglu ◽  
Demet Sinem Guden ◽  
Ozden Vezir ◽  
Nehir Sucu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Signaling Pathway ◽  
Inducible Nitric Oxide Synthase ◽  
Nitrosative Stress ◽  
Ischemia Reperfusion ◽  
Mammalian Target Of Rapamycin ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Mammalian target of rapamycin (mTOR) has been recognized with potential immunomodulatory properties playing an important role in various physiopathological processes including ischemia–reperfusion (I/R) injury. I/R injury stimulate reactive oxygen and nitrogen species by activating nicotinamide adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase, respectively. Controversial results have been obtained in different I/R models following localized I/R; however, the precise role of the mTOR signaling pathway remains undefined. The objective of the current study was to evaluate the role of the mTOR in oxidative–nitrosative stress and inflammation in hindlimb I/R-induced injury in target and remote organ injuries. In rats subjected to I/R, an increased expression of ribosomal protein S6 (rpS6), inhibitor κB (IκB)-α, nuclear factor-κB (NF-κB) p65, inducible nitric oxide synthase, cyclooxygenase 2, gp91phox, and levels of tumor necrosis factor α, nitrite, nitrotyrosine, malondialdehyde and the activities of myeloperoxidase and catalase in the tissues and (or) sera were detected. Treatment with rapamycin, a selective inhibitor of mTOR, reversed all the I/R-induced changes as manifested by its anti-inflammatory and antioxidant effects in kidney and gastrocnemius muscle of rats. Collectively, these findings suggest that rapamycin protects against I/R-induced oxidative–nitrosative stress and inflammation leading to organ injuries via suppression of mTOR/IκB-α/NF-κB signaling pathway.

scholarly journals Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Azza A. K. El-Sheikh ◽  
Mohamed A. Morsy ◽  
Ahlam M. Abdalla ◽  
Azza H. Hamouda ◽  
Ibrahim A. Alhaider
Keyword(s):  
Nitric Oxide ◽  
Nitrosative Stress ◽  
Oxidative And Nitrosative Stress ◽  
Liver Functions ◽  
Apoptotic Effect ◽  
Liver And Kidney ◽  
Hepatic Histology ◽  
Oxide Synthase ◽  
Necrosis Factor ◽  
Inducible Nitric Oxide

To investigate mechanisms by which thymoquinone (TQ) can prevent methotrexate- (MTX-) induced hepatorenal toxicity, TQ (10 mg/kg) was administered orally for 10 days. In independent rat groups, MTX hepatorenal toxicity was induced via 20 mg/kg i.p. at the end of day 3 of experiment, with or without TQ. MTX caused deterioration in kidney and liver function, namely, blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase. MTX also caused distortion in renal and hepatic histology, with significant oxidative stress, manifested by decrease in reduced glutathione and catalase, as well as increase in malondialdehyde levels. In addition, MTX caused nitrosative stress manifested by increased nitric oxide, with upregulation of inducible nitric oxide synthase. Furthermore, MTX caused hepatorenal inflammatory effects as shown by increased tumor necrosis factor-α, besides upregulation of necrosis factor-κB and cyclooxygenase-2 expressions. MTX also caused apoptotic effect, as it upregulated caspase 3 in liver and kidney. Using TQ concurrently with MTX restored kidney and liver functions, as well as their normal histology. TQ also reversed oxidative and nitrosative stress, as well as inflammatory and apoptotic signs caused by MTX alone. Thus, TQ may be beneficial adjuvant that confers hepatorenal protection to MTX toxicity via antioxidant, antinitrosative, anti-inflammatory, and antiapoptotic mechanisms.

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