Serum concentrations and renal expressions of IL-1 and TNF-a early after hemorrhage in rats under the effect of glibenclamide

ABSTRACT PURPOSE: To investigate changes in the serum concentration and renal expression of IL-1 and TNF-α cytokines in rats that received sevoflurane and glibenclamide prior to hemorrhage. METHODS: Two groups of sevoflurane-anesthetized Wistar rats (n=10): G1 (control) and G2 (glibenclamide, 1 µg/g i.v.); hemorrhage of 30% blood volume (10% every 10 min), with replacement using Ringer solution, 5 ml/kg/h. Serum concentrations of IL-1 and TNF-α were studied in the first hemorrhage (T1) and 50 min later (T2), renal expression, at T2. RESULTS: In serum, G1 TNF-α (pg/mL) was T1=178.6±33.5, T2=509.2±118.8 (p<0.05); IL-1 (pg/mL) was T1=148.8±31.3, T2=322.6±115.4 (p<0.05); in G2, TNF-α was T1=486.2±83.6, T2=261.8±79.5 (p<0.05); IL-1 was T1=347.0±72.0, T2= 327.3±90.9 (p>0.05). The expression of TNF-α and IL-1 in the glomerular and tubular cells was significantly higher in the G2 group. CONCLUSIONS: Hemorrhage and glibenclamide elevated TNF-α and IL-1 concentrations in serum and kidneys. High levels of TNF-α already present before the hemorrhage in the glibenclamide group may have attenuated the damages found in the kidneys after the ischemia event.

Efeito protetor do Nitrosil-Rutênio (Cis[Ru(bpy)2SO3NO]+(PF6) em modelos experimentaisde lesões gástricas em camundongos – envolvimento da via NO/GCS/KATP

Lesões gástricas relacionadas ao consumo excessivo de antiinflamatórios não esteroidais (AINEs) e etanol possuem um importante papel na gastroenterologia clínica. Fármacos com ação anti-secretória gástrica, como os inibidores da bomba de prótons, representam a principal opção na terapia destas patologias. Objetivo: Avaliar o efeito do doador de NO nitrosil-rutênio (Rut-NO) na defesa da mucosa gástrica em modelos experimentais de lesão gástrica em camundongos e a participação da guanilato ciclase solúvel (GCs) e dos canais de KATP neste efeito. Métodos: Protocolo1-Camundongos swiss foram pré-tratados com Rut-NO (3mg/Kg, v.o), rutênio (2.3mg/Kg, v.o) ou nitroprussiato (NPS) na dose de 10mg/kg, v.o, meia hora antes da administração por gavagem de etanol 50%. Em outro grupo, os animais foram pré-tratados com ODQ (10mg/Kg, v.o) ou glibenclamida (10mg/Kg,i.p) trinta minutos ou 1h antes, respectivamente dos tratamentos citados anteriormente.Depois de 1h, os animais foram sacrificados e os estômagos removidos para a avaliação das lesões gástricas por planimetria computadorizada. Além disso, fragmentos de tecido foram removidos para análise microscópica e dosagem de glutationa (GSH) e malondialdeído (MDA)...

Gastric lesions associated to excessive consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol have an important role in clinical gastroenterology. The drugs with gastric antisecretory action, suchas proton pump inhibitors, represent the main option in the treatment of these pathologies. Aim: To evaluate the effect of NO donor nitrosyl-ruthenium (Rut-NO) in gastric mucosal defense in experimental models of gastric damage in mice, as wellthe involvement of soluble guanylate cyclase (sGC) and KATPchannels in this effect. Methods: Protocol 1-mice were pre-treated with Rut-NO (3mg/Kg, vo), ruthenium (2.3mg/Kg, p.o) or nitroprusside (SNP) at a dose of 10mg/kg, p.o, half an hour before administration by gavage of 50% ethanol. In another group, the animals were pre-treated with ODQ (10mg/kg, po) or glibenclamide (10mg/kg, ip) thirty minutes or 1 hour prior, respectively,the treatments mentioned above. After 1h, the animals were sacrificed and the stomachsremoved for evaluation of gastric lesions by computerized planimetry. In addition, fragments of tissue were removed for microscopic analysis and measurement of glutathione (GSH) and malondialdehyde (MDA) levels...

Mechanisms Involved in Exercise-Induced Cardioprotection: A Systematic Review / Mecanismos Envolvidos na Cardioproteção Induzida pelo Exercício Físico: Uma Revisão Sistemática

Acute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing cardiovascular risk factors, can also protect the heart against injury due to ischemia and reperfusion through a direct effect on the myocardium. However, the specific mechanism involved in exerciseinduced cardiac preconditioning is still under debate.

O infarto agudo do miocárdio é a principal causa de mortalidade e de morbidade na população mundial. Por outro lado, pesquisas já demonstraram que o exercício físico, além de reduzir os fatores de risco cardiovascular, também é capaz de promover cardioproteção contra lesões por isquemia e reperfusão, por meio de um efeito direto no miocárdio. No entanto, o mecanismo específico envolvido no pré-condicionamento cardíaco induzido pelo exercício ainda é alvo de discussão.

The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats

Our objective was to investigate the protective effect of Lawesson's reagent, an H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm2); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm2); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (KATP) channels.

Influence of two hypoglycemic Cucurbitaceae (Cucurbita ficifolia Bouché and Ibervillea sonorae Greene) on ATP-sensitive potassium channels in rat aortic rings / Influencia de dos Cucurbitaceae (Cucurbita ficifolia Bouché e Ibervillea sonorae Greene) sobre los canales de potasio sensibles a ATP en anillos aórticos de rata

Cucurbita ficifolia Bouché fruit containing D-chiro-inositol and Ibervillea sonorae Greene root containing cucurbitane-type glycosides are used to control diabetes in Mexico. Although the hypoglycemic effect of both plants has been demonstrated and some active compounds proposed, their mechanisms are still unknown. The aim of this study was to determine if the incubation with both aqueous extracts avoids the inhibition of contraction induced by phenylephrine similarly to glibenclamide in rat aortic rings. The hypoglycemic aqueous extracts of C. ficifolia and I. sonorae were characterized for their content of either D-chiro inositol or cucurbitanes respectively, and then we assayed the characterized extracts in vitro on the diazoxide-induced relaxation of rat aortic rings precontracted with phenylephrine, using as positive control glibenclamide. I. sonorae extract blocked the KATP channels in a concentration-dependent manner (p < 0.05), whereas C. ficifolia extract had no effect on these channels. I. sonorae extract produces a hypoglycemic effect through a similar mechanism to sulphonylureas in this experimental model; however, hypoglycemic action of C. ficifolia extract should be explained by an independent KATP channels mechanism.

Los frutos de Cucurbita ficifolia conteniendo D-quiro-inositol y las raíces de Ibervillea sonorae conteniendo glucósidos tipo cucurbitano son empleados en el control de la diabetes en México. Aunque el efecto hipoglucémico de ambas plantas ha sido demostrado y se han propuesto algunos de sus compuestos activos, aún se desconoce su mecanismo de acción. El objetivo de este estudio fue determinar si la incubación con ambos extractos acuosos evita la inhibición de la contracción inducida por fenilefrina de manera similar a la glibenclamida en anillos aórticos de rata. Los extractos acuosos hipoglucémicos de C. ficifolia e I. sonorae fueron caracterizados en su contenido de D-quiro inositol o cucurbitanos, respectivamente y entonces fueron estudiados en un modelo in vitro en la relajación inducida por diazóxido en anillos aórticos previamente contraídos con fenilefrina, usando como control positivo glibenclamida. El extracto de Ibervillea sonorae bloqueó los canales KATP de manera dosis-dependiente (p < 0.05), mientras que Cucurbita ficifolia no tuvo efecto en esos canales. El extracto de I. sonorae produce efecto hipoglucémico a través de un mecanismo similar al de las sulfonilureas en este modelo experimental; por su parte, la acción hipoglucemiante del extracto de C. ficifolia debe ser explicado mediante un mecanismo independiente de los canales KATP.

Participation of the NO/cGMP/K+ATP pathway in the antinociception induced by Walker tumor bearing in rats

Implantation of Walker 256 tumor decreases acute systemic inflammation in rats. Inflammatory hyperalgesia is one of the most important events of acute inflammation. The L-arginine/NO/cGMP/K+ATP pathway has been proposed as the mechanism of peripheral antinociception mediated by several drugs and physical exercise. The objective of this study was to investigate a possible involvement of the NO/cGMP/K+ATP pathway in antinociception induced in Walker 256 tumor-bearing male Wistar rats (180-220 g). The groups consisted of 5-6 animals. Mechanical inflammatory hypernociception was evaluated using an electronic version of the von Frey test. Walker tumor (4th and 7th day post-implantation) reduced prostaglandin E2- (PGE2, 400 ng/paw; 50 µL; intraplantar injection) and carrageenan-induced hypernociception (500 µg/paw; 100 µL; intraplantar injection). Walker tumor-induced analgesia was reversed (99.3% for carrageenan and 77.2% for PGE2) by a selective inhibitor of nitric oxide synthase (L-NAME; 90 mg/kg, ip) and L-arginine (200 mg/kg, ip), which prevented (80% for carrageenan and 65% for PGE2) the effect of L-NAME. Treatment with the soluble guanylyl cyclase inhibitor ODQ (100% for carrageenan and 95% for PGE2; 8 µg/paw) and the ATP-sensitive K+ channel (KATP) blocker glibenclamide (87.5% for carrageenan and 100% for PGE2; 160 µg/paw) reversed the antinociceptive effect of tumor bearing in a statistically significant manner (P < 0.05). The present study confirmed an intrinsic peripheral antinociceptive effect of Walker tumor bearing in rats. This antinociceptive effect seemed to be mediated by activation of the NO/cGMP pathway followed by the opening of KATP channels.

Diabetes melito neonatal: [revisão] / Neonatal diabetes mellitus: [review]

O diabetes neonatal (DN) é uma condição rara caracterizada por hiperglicemia, que necessita de tratamento com insulina, diagnosticado nos primeiros meses de vida. Clinicamente pode ser classificado em DN transitório quando ocorre remissão da doença em poucos meses, podendo haver recorrência posterior; ou permanente quando, como o nome indica, não ocorre remissão. Ambas as condições são geneticamente heterogêneas; entretanto a maioria dos casos de DN transitório é decorrente de anormalidades da região de imprinted no cromossomo 6q24. Mutações ativadoras em heterozigose no gene KCNJ11, que codifica a subunidade Kir6.2 do canal de potássio ATP-sensível, são a causa mais comum de DN permanente. No presente artigo, discutimos as características clínicas do DN, os mecanismos moleculares envolvidos e suas implicações terapêuticas.

Neonatal diabetes is a rare condition characterized by hyperglycemia, requiring insulin treatment, diagnosed within the first months of life. The disorder may be either transient, resolving in infancy or early childhood with possible relapse later, or permanent in which case lifelong treatment is necessary. Both conditions are genetically heterogeneous; however, the majority of the cases of transient neonatal diabetes are due to abnormalities of an imprinted region of chromosome 6q24. For permanent neonatal diabetes, the most common causes are heterozygous activating mutations of KCNJ11, the gene encoding the Kir6.2 sub-unit of the ATP-sensitive potassium channel. In this article we discuss the clinical features of neonatal diabetes, the underlying genetic defects and the therapeutic implications.