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1.
Exp Eye Res ; 132: 190-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25662313

RESUMO

Hydrogen sulphide (H2S) is known to be produced endogenously in ocular tissues with the highest levels in the retina and cornea. However, it is yet unclear whether it can modulate retinal arterial tone. Herein, we aimed to investigate the effectiveness and the mechanism of the action of H2S in the isolated bovine retinal arteries. For this purpose, the probable vasorelaxant and inhibitory effects of H2S on vascular reactivity were tested comparatively in the retinal arteries by using the donor, sodium hydrosulphide (NaHS). Thereafter, in relation to the mechanism of action of H2S, the role of nitric oxide (NO) and endothelial vasodilators of cyclooxygenase pathway as well as ATP-sensitive potassium channel (KATP), voltage-dependent potassium channel (Kv), calcium-activated potassium channel (KCa(++)), inwardly rectifying potassium channel (Kir), L-type voltage-dependent calcium channel and adenylate cyclase pathway were evaluated. NaHS (1µM-3mM) displayed prominent relaxations over the concentrations of 300 µM in both PGF2α and K(+) precontracted retinal arteries. Comparatively, in the presence of NaHS (3 mM) pretreatment, the maximum contractile responses and pEC50 values to PGF2α and K(+) were significantly reduced as well. Neither the presence of the known inhibitors of NO synthase, guanylate cyclase, cyclooxygenase, adenylate cyclase, KATP and KCa(++) type K(+) channels, and L-type voltage-dependent calcium channels nor the removal of endothelium, modified the relaxation response to NaHS in retinal arteries. However, a remarkable decrease was observed in the presence of the inhibitors of Kv or Kir type K(+) channels. In addition, administration of l-cysteine (1µM-3mM), the precursor of H2S, induced a modest relaxation response in PGF2α precontracted retinal arteries, which was significantly decreased in the presence of cystathionine-ß-synthase (CBS) inhibitor, aminooxyacetic acid, but was unmodified in the presence of the cystathionine-γ-lyase (CSE) inhibitor, dl-propargylglycine or the deendothelization of retinal arteries. Our findings suggested that H2S might play a substantial role in the regulation of retinal arterial tone possibly by acting on Kv and Kir channels.


Assuntos
Canais de Potássio/efeitos dos fármacos , Prostaglandinas F/fisiologia , Artéria Retiniana/fisiologia , Sulfetos/farmacologia , Vasodilatação , Vasodilatadores/farmacologia , Análise de Variância , Animais , Canais de Cálcio Tipo L/fisiologia , Bovinos , Cisteína/farmacologia , Endotélio/fisiologia , Sulfeto de Hidrogênio/farmacologia , Canais de Potássio/fisiologia , Artéria Retiniana/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia
2.
Biotech Histochem ; 93(1): 70-75, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29363342

RESUMO

We investigated the histopathological effects of methotrexate (MTX), a chemotherapeutic agent, and beta glucan (BG), an antioxidant, on rat testis. We used four groups of Sprague-Dawley male rats: MTX, MTX + BG, BG, and control. The MTX group was exposed to a single dose of MTX on the first day of experiment. The MTX + BG group was exposed to a single dose of MTX and BG on the first day of experiment followed by BG for 4 additional days. The BG group was exposed to BG for 5 days. The control group was given saline for 5 days. On day five, all animals were sacrificed and testicular tissue was evaluated for histopathology and the terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate nick-end labeling assay (TUNEL) was used to detect apoptosis. The apoptotic index (AI) and testicular damage increased in the MTX group compared to the other three groups. Histopathology was reduced in the MTX + BG group compared to the MTX group. Seminiferous tubule diameter was reduced in the MTX group compared to the BG group; we found no difference between control and BG groups. The thickness of th e germinal epithelium was reduced in the MTX group compared to the other groups. We found no difference in testicular weight among the groups. We compared body weight before and after the experiment; weights in the MTX and MTX + BG groups were significantly reduced compared to controls. In the control groups, we found a statistically significant increase in body weight, whereas there was no change in the BG group. We found that MTX causes deleterious effects on testicular tissue and that beta glucan may be protective.


Assuntos
Metotrexato , Testículo/efeitos dos fármacos , beta-Glucanas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Masculino , Metotrexato/toxicidade , Ratos , Ratos Sprague-Dawley , Padrões de Referência , Testículo/patologia
3.
Biotech Histochem ; 93(1): 8-14, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29215307

RESUMO

We investigated the possible neuroprotectant and intraocular pressure (IOP) lowering effects of intravitreous injection of sodium hydrosulfide (NaSH) in a rodent model of experimental glaucoma. Glaucoma currently is treated by controlling IOP using medications and/or surgery. These methods are not entirely adequate for all patients. We divided 24 rats into three groups. For the control group, the right eye was treated with intravitreous saline. For the glaucoma group, ocular hypertension was induced by photocoagulating three episcleral veins and the limbal plexus of the right eye using an argon laser, then saline was injected into the vitreous of these eyes during the third week. For the NaSH group, rats were treated with intravenous NaSH 3 weeks after photocoagulation. IOP was measured each week during the 6 week experimental period. Coagulating the episcleral veins rapidly increased the IOP of rat eyes. Intravitreous injection of NaSH significantly reduced IOP. Intravitreous NaSH prevented degeneration of the retina and decreased the number of apoptotic cells. Intravitreous NaSH appeared to reduce IOP and to prevent IOP induced retinopathy in rats.


Assuntos
Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/tratamento farmacológico , Sulfetos/farmacologia , Administração Intravenosa , Animais , Apoptose , Modelos Animais de Doenças , Citometria de Fluxo , Glaucoma/tratamento farmacológico , Ratos , Padrões de Referência , Retina/patologia , Sulfetos/administração & dosagem
4.
Pharmacogn Mag ; 11(41): 163-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25709228

RESUMO

BACKGROUND: In the last decade, a growing interest particularly in determining the cardiovascular effects of herbal extracts took place among researchers. OBJECTIVE: Herein, we aimed to investigate the microvascular and blood pressure lowering effects of two differently processed extracts of the same herb, Alchemilla vulgaris (Rosaceaea), which was revealed to contain high levels of vasoactive compounds. MATERIALS AND METHODS: For the purpose, endothelium intact rat mesenteric arteries were mounted in a myograph system and contracted with prostaglandin F2α (PGF2α: 3 × 10(-5) M) or potassium chloride (K(+): 40 mM). Then, aqueous and methanol extracts were added at 0.01-10 mg/ml concentrations in a cumulative manner. RESULTS: Both extracts produced relaxations in PGF2α (3 × 10(-5) M) precontracted arteries which were insensitive to the inhibitors of endothelium derived vasoactive substances namely, L(G)-nitro-L-arginine (10(-4) M), ODQ (10(-5) M) and indomethacin (10(-5) M) or removal of endothelium. Opposite vascular effects were observed when extracts were applied in K(+) precontracted arteries. In addition, oral administration of the methanol extract of Alchemilla vulgaris, but not the aqueous extract, reduced blood pressure significantly in L-NAME hypertensive rats. CONCLUSION: Our results demonstrated that the methanol extract of Alchemilla vulgaris has more prominent and favourable vascular effects in normal and experimental hypertensive conditions reinforcing its traditional use in cardiovascular disorders, in particular hypertension. These results most likely give rise to further studies to reveal its mechanism of action and clinical value of this herb.

5.
Nat Prod Res ; 28(23): 2182-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24938755

RESUMO

We aimed to investigate the vascular effects of methanol extract (ME) and aqueous extract (AE) of Alchemilla vulgaris (Rosaceaea). Increasing concentrations of the ME (0.01-10 mg/mL) produced relaxations in noradrenaline (NA: 10⁻6 M) and K⁺ (40 mM) precontracted aortas while contractions were obtained with the AE (0.01-10 mg/mL). Responses to the ME were inhibited in the presence of putative inhibitors of endothelial vasodilators or after removal of the endothelium. Pretreatment of aortic rings with the ME (10 mg/mL, 20 min) reduced the maximal contractions to NA and K⁺, whereas an enhanced contractility was observed with the AE (10 mg/mL, 20 min). Total flavonoid content was higher in the ME than in the AE. Quercetin was determined particularly high in the ME while gallic acid was high in the AE. Our results indicated that the ME of A. vulgaris displays favourable vascular effects via endothelium-dependent mechanisms.


Assuntos
Aorta/efeitos dos fármacos , Endotélio/metabolismo , Flavonoides/farmacologia , Vasodilatadores/farmacologia , Alchemilla , Animais , Flavonoides/análise , Flavonoides/química , Metanol , Ratos , Água
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