Protective effect of L-arginine on gentamicin-induced nephrotoxicity in rats

PubMedID: 25538331Introduction: L-arginine has a protective effect on gentamicin-induced renal failure and it may decrease the tubular reabsorption of another cationic substance, gentamicin due to its cationic structure. The aim of this study is to compare the possible protective effects of L-arginine and its inactive isomer D-arginine on gentamicin-induced nephrotoxicity in rats. Materials and Methods: Wistar albino rats were housed in metabolic cages and assigned to six groups as: control group, gentamicin (100 mg/kg), gentamicin + L-arginine (2 g/l), gentamicin + D-arginine (2 g/l), gentamicin + L-arginine + Nv-nitro-L-arginine methyl ester (L-NAME) (100 mg/l) and gentamicin + D-arginine + L-NAME. Gentamicin was administered by subcutaneous injections and the other drugs were added in drinking water for seven consecutive days. The animals were killed by decapitation and intracardiac blood and urine samples were obtained on the seventh day. Blood urea nitrogen, serum creatinine, sodium, potassium, urine gamma glutamyl transferase, creatinine, sodium, potassium and gentamicin levels were measured using High Performance Liquid Chromatography (HPLC) technique. Results: Gentamicin treated group had significant increase in blood urea nitrogen, serum creatinine, fractional Na excretion and urine gamma glutamyl transferase levels, and significant decrease in creatinine clearance compared to the control group. L-arginine and D-arginine reversed these findings. L-NAME abolished the nephroprotective effect of L-arginine. The urinary levels of gentamicin were significantly increased in rats treated with L-arginine or D-arginine compared to those treated with gentamicin. L-arginine and D-arginine reversed the advanced degenerative changes due to gentamicin administration in histopathological examination. Conclusion: Our study revealed the protective effect of L-arginine on gentamicin-induced nephrotoxicity, the contribution of the cationic feature of L-arginine, and the major role of NO in this protective effect

Neocuproine, a copper (I) chelator, potentiates purinergic component of vas deferens contractions elicited by electrical field stimulation

PubMedID: 16020948Effects of the specific copper (I) chelator, neocuproine, on the purinergic and adrenergic components of nerve-evoked contractions were investigated in the prostatic rat vas deferens. Electrical field stimulation (EFS; 4 Hz) induced bimodal contractions of vas deferens tissue in the presence of ?1-adrenoceptor antagonist prazosin (to isolate the purinergic component) or purinoceptor antagonist suramin (to isolate the adrenergic component). Neocuproine significantly potentiated the purinergic component of the contractile responses to EFS. However, the same agent failed to elicit any significant effect on the adrenergic component of nerve-evoked contractions. The copper (II) chelator cuprizone could not affect the purinergic component of contractions. The potentiating effect of neocuproine which was reversible after washout of the drug, did not occur following the application of the pre-prepared neocuproine-copper (I) complex. A nitric oxide synthase inhibitor, L-nitroarginine; a cyclooxygenase inhibitor, indomethacin or an ?2-adrenoceptor antagonist, yohimbine, failed to alter the responses to neocuproine on the purinergic component of the contraction to EFS. Neocuproine did not elicit any significant effect on preparations in which the purinergic receptors were desensitized with ?,ß-methylene ATP. In conclusion, our results suggest that neocuproine potentiates the purinergic component of rat vas deferens contractions elicited by EFS, presumably by facilitating purinergic neurotransmission and that copper (I)-sensitive mechanisms can modulate purinergic transmission in this tissue. Copyright © 2005 S. Karger AG

Comparative study of the quercetin, ascorbic acid, glutathione and superoxide dismutase for nitric oxide protecting effects in mouse gastric fundus

PubMedID: 23085029The aim of this work was to compare the preventing capacity of quercetin with Cu/Zn superoxide dismutase (Cu/Zn SOD), ascorbic acid and glutathione on nitric oxide (NO)-induced relaxation in mouse gastric fundus. Furthermore, the effects of the quercetin on the tissue level of total oxidant and antioxidant was investigated. Nitrergic stimulation (4 Hz, 25 V, 0.1 ms, 10 s-train) and exogenous NO (10 µM) induced relaxation. Pyrogallol (10 µM), hydroquinone (100 µM) and LY83583 (6-Anilino-quinolin-5,8-quinone, 5 µM) inhibited nitrergic relaxations. The inhibition observed with pyrogallol, hydroquinone and LY83583 was prevented by quercetin (0.1 µM). Also, ascorbic acid (500 µM), glutathione (100 µM) and Cu/Zn SOD (100 U/ml) prevented the inhibitory effect of superoxide anion generators on the relaxation to nitrergic stimulation and NO. Diethyldithiocarbamic acid (DETCA; 8 mM) inhibited nitrergic relaxations. DETCA-induced inhibition on nitrergic stimulation and NO-induced relaxation was prevented by quercetin, ascorbic acid, glutathione or Cu/Zn SOD. DETCA plus pyrogallol, hydroquinone or LY83583 strengthened the inhibition on the relaxations. Also, pre-treatment with quercetin, ascorbic acid and glutathione prevented the inhibitory effect of DETCA plus LY-83583 on the relaxation to nitrergic stimulation and NO but Cu/Zn SOD did not prevent this inhibition. Also, quercetin increased tissue total antioxidant capacity and decreased tissue oxidant level and oxidative stress index in DETCA-treatment group. These results indicate that quercetin has antioxidant effect and protects NO from endogenous superoxide anion-driven inactivation and enhances its biological activity, suggesting that quercetin may scavenge superoxide anion in a Cu/Zn SOD, glutathione or ascorbic acid-inhibitable manner. © 2012 Elsevier B.V. All rights reserved.TF2005BAP22This work was supported by Çukurova University Research Foundation ( TF2005BAP22

Antioxidant effects of a poliphenolic compound quercetin in mouse corpus cavernosum

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Enhancement of EFS-induced adrenergic contractions by treatment of Levamisole in the mouse corpus cavernosum

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Dose-dependent differential mechanism of quercetin-induced vasodilatations in isolated perfused rat mesenteric vascular bed

Epidemiological studies indicate that low incidence of cardiovascular disease is associated with dietary intake of polyphenolic compounds, which are abundantly present in fruits and vegetables. There is solid evidence that quercetin, a polyphenolic compound, exerts vasodilator effects in addition to its antioxidant activity. Therefore, in this study, the contribution of shear stress-induced nitric oxide to the vasodilator effect of quercetin in mesenteric bed was investigated. Dose-dependent vasodilator effects of quercetin on the perfusion pressure increased by phenylephrine were recorded in the presence of L-arginine/cGMP pathway inhibitors or superoxide dismutase in the perfused mesenteric vascular beds isolated from rats. Quercetin (1, 5 and 10 µM) concentration-dependently decreased the perfusion pressure raised by phenylephrine (3-6 µM) in the endothelium-intact mesenteric bed. The relaxations occured at 1 and 5 µM quercetin were significantly inhibited by nitric oxide synthase inhibitor, N?-nitro-L-arginine (L-NA,100 µM) or the guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 5 µM), while relaxations to 10 µM quercetin were not affected. Removal of endothelium significantly reduced the relaxations at lower concentrations of quercetin but was without effect on relaxations induced by 10 µM. Calmidazolium (0.5 µM), a calmodulin inhibitor did not significantly affect the quercetin responses but a superoxide anion scavanger, superoxide dismutase (SOD, 100 U mL-1) significantly improved the quercetin-induced relaxations especially at 1 and 5 µM. These findings suggest that quercetin induces endothelium-dependent vasodilatations at lower concentrations by increasing the bioactivity of sustained nitric oxide release evoked by perfusion pressure. However, the vasodilatations induced by high concentrations of quercetin are endothelium-independent. © 2016 Ozlem Yorulmaz Ozü et al

Possible nature of mediator responsible for electrically-induced relaxations in the longitudinal muscle preparation of mouse gastric fundus

The effect of a nitric oxide synthase inhibitor, N(G)-nitro L-arginine (L- NNA) and its interaction with L-arginine, D-arginine and L-citrulline on the relaxations evoked by electrical field stimulation were investigated in the longitudinal muscle strips of the mouse gastric fundus precontracted with carbachol. L-NNA inhibited the electrically-induced relaxations in a concentration-dependent and significant manner. The inhibitory effect of L- NNA was prevented by L-arginine but not by D-arginine. L-citrulline partially prevented the L-NNA action. These results suggest that nitric oxide (NO) is involved in the electrically-induced relaxations of the longitudinal muscle strips of the mouse gastric fundus

Papaverine-induced and endothelium-dependent relaxation in the isolated rat aortic strip

PubMedID: 10488403In the present study, we aimed to obtain further evidence in favour of the hypothesis that nitric oxide (NO) is a major mediator of endothelium-dependent vasorelaxation and to clarify whether NO plays a role in papaverine-induced vasorelaxation. The relaxant effects of acetylcholine (Ach), acidified NaNO2 or papaverine were investigated on isolated helical strips of the rat thoracic aorta precontracted with phenylephrine in an organ bath containing Krebs solution aerated with 95% O2 and 5% CO2. The relaxation was quantified as % peak reduction of phenylephrine contracture. Saponin abolished the relaxant effects of Ach completely whereas it had no effect on the responses to acidified NaNO2 or papaverine. NG-nitro-L-arginine (L-NOARG) reduced the effects of Ach significantly, but it was ineffective on the relaxation induced by acidified NaNO2. The inhibitory action of L-NOARG was partly restored by L-arginine, but not by D-arginine. Hemoglobin, hydroxocobalamin and hydroquinone exhibited significant inhibition on the relaxation evoked by Ach and acidified NaNO2. L-NOARG, hydroxocobalamin and hydroquinone caused only limited but significant decrease in the relaxation due to papaverine. This phenomenon was also observed by increasing phenylephrine concentration leading to an enhancement in the contraction. Our findings strongly support the view that Ach-induced relaxation of rat aorta strips is mediated by free NO released from the endothelium and the results suggest that NO may indirectly contribute to papaverine-induced relaxation

Effects of some divalent cations on nitrergic relaxations in the mouse corpus cavernosum

PubMedID: 11903503Acute effects of some divalent cations (Cd2+, Ni2+, Co2+, Zn2+, Mn2+ and Sn2+) were investigated on neurogenic and endothelium-dependent relaxations in the isolated mouse corpus cavernosum. Neither neurogenic nor endothelium-dependent relaxation was affected by cations at the concentrations used (up to 100 µM), except Cd2+. Although Cd2+ (20 and 40 µM) did not cause any significant alteration in the acetylcholine- (ACh) or sodium nitroprusside- (SNP) induced relaxation, it inhibited electrical field stimulation-(EFS) produced relaxation significantly. Zn2+ and selenium could not reverse this inhibitory action. Cd2+ did block the EFS-evoked guanethidine-sensitive contraction in the presence of NG-nitro-L-arginine. Elevation of external Ca2+ content significantly reduced the inhibitions due to Cd2+ on the EFS-induced relaxation and on the EFS-evoked guanethidine-sensitive contraction. In the Ca2+-omitted medium, EFS-induced relaxation disappeared, while acetylcholine-elicited relaxation resisted. Verapamil was ineffective on the relaxation produced by EFS or acetylcholine. However, it significantly diminished phenylephrine-induced contractions. These findings suggest that unlike other cations at the concentrations used in the present study, Cd2+ may have an effect on an external Ca2+-dependent mechanism at the neuronal level, and this effect may be responsible for its acute inhibitory action on the neurogenic relaxation in the mouse corpus cavernosum

Effect of tempol (4-hydroxy-tempo) on gentamicin-induced nephrotoxicity in rats

International Symposium on Vascular NO - From Bench to Bedside -- MAR 11-13, 2004 -- Hannover, GERMANYWOS: 000235546400052