Effect of naringerin on biochemical parameters in the streptozotocin-induced diabetic rats

Dentre as numerosas terapias para minimizar as complicações diabéticas, os antioxidantes e flavonoides são testados na clínica médica. Foi analisado o efeito da naringerina sobre os parâmetros bioquímicos em ratos diabéticos induzidos por estreptozotocina (STZ - 60mg/kg, i.p.). Ratos machos foram divididos em 4 grupos: G1: controle não tratado; G2: ratos normais que receberam naringerina; G3: diabéticos não tratados; G4: ratos diabéticos que receberam naringerina. Naringerina (50mg/kg, i.p.), decresceu a hiperglicemia e a hiperlipidemia em ratos diabéticos. A concentração sérica de insulina em ratos tratados tendeu aumentar. A naringerina preveniu as alterações, provocadas pela estreptozotocina, na atividade hepática e cardíaca de ALT, AST e LDH, indicando o efeito protetor da naringerina sobre estes tecidos, contra toxicidade provocada pela STZ. O nível de glicogênio nos tecidos cardíaco e hepático elevou com a naringerina em ratos diabéticos. A naringerina melhorou o metabolismo da glicose e de lipídios e preveniu as complicações diabéticas.

Formyl-peptide receptor is not involved in the protection afforded by annexin 1 in murine acute myocardial infarct

Recent interest in the annexin 1 field has come from the notion that specific G-protein-coupled receptors, members of the formyl-peptide receptor (FPR) family, appear to mediate the anti-inflammatory actions of this endogenous mediator. Administration of the annexin 1 N-terminal derived peptide Ac2-26 to mice after 25 min ischemia significantly attenuated the extent of acute myocardial injury as assessed 60 min postreperfusion. Evident at the dose of 1 mg/kg (similar to9 nmol per animal), peptide Ac2-26 cardioprotection was intact in FPR null mice. Similarly, peptide Ac2-26 inhibition of specific markers of heart injury (specifically myeloperoxidase activity, CXC chemokine KC contents, and endogenous annexin 1 protein expression) was virtually identical in heart samples collected from wild-type and FPR null mice. Mouse myocardium expressed the mRNA for FPR and the structurally related lipoxin A(4) receptor, termed ALX; thus, comparable equimolar doses of two ALX agonists (W peptide and a stable lipoxin A4 analog) exerted cardioprotection in wild-type and FPR null mice to an equal extent. Curiously, marked (>95%) blood neutropenia produced by an anti-mouse neutrophil serum did not modify the extent of acute heart injury, whereas it prevented the protection afforded by peptide Ac2-26. Thus, this study sheds light on the receptor mechanism(s) mediating annexin 1-induced cardioprotection and shows a pivotal role for ALX and circulating neutrophil, whereas it excludes any functional involvement of mouse FPR. These mechanistic data can help in developing novel therapeutics for acute cardioprotection.

Myocardial protection by continuous, blood, antegrade-retrograde cardioplegia in rabbits

OBJETIVO: Estudar a eficácia e a segurança da cardioplegia sanguínea, aterógrada-retrógrada contínua, por meio da avaliação da função ventricular. MÉTODOS: Os coelhos foram divididos em quatro grupos: Controle-C(n=10); isquêmico e cardioplegia cristaloide-IC(n=10; isquêmico e cardioplegia sanguínea-IB(n=10; isquêmico sem cardioplegia-INC(n=10. Após o período isquêmico do protocolo a função ventricular foi analisada pela técnica do balão intra-ventricular. RESULTADOS: a pressão desenvolvida intra-ventricular (IVDP) foi: C(92,90± 6,86mmHg); IC(77,78± 6,15mmHg); IB(93,64 ±5,09mmHg); INC(39,46 ±8,91mmHg) p<0,005. a primeira derivada temporal da pressão ventricular na sua deflexão positiva: C(1137,50± 92,23mmHg/sec); IC(1130,62 ±43,78mmHg/sec); IB(1187,58± 88,38mmHg/sec); INC(620,02± 43,80mmHg/se) p<0,005. A primeira derivada da pressão ventricular na sua deflexão negativa: C(770,00± 73,41mmHg/sec); IC(610,03 ±47,43mmg/sec); IB(762,53 ±46,02mmHg/sec); INC(412,35 ±84,36mmHg/sec) p<0,005. A relação do coeficiente angular logarítmico foi: C(0,108± 0,02); IC(0,159± 0,038); IB(0,114 ±0,016); INC(0,175± 0,038) p<0,05. CONCLUSÃO: No modelo experimental estudado o grupo isquêmico protegido pela cardioplegia sanguínea apresentou melhor função ventricular que os grupos protegidos por cardioplegia cristalóide e não protegido.

Stress-induced subsensitivity to catecholamines depends on the estrous cycle

In this article we compare how sensitivity to the chronotropic effect of noradrenaline and adrenaline of right atria isolated from female rats is modified after repeated swimming or foot-shock stress, under the influence of the estrous cycle. Right atria from stressed female rats sacrificed at diestrus were subsensitive to both catecholamines, irrespective of the stressor agent. However, although subsensitivity to noradrenaline was of similar intensity, subsensitivity to adrenaline was more pronounced in right atria from foot shock stressed rats as opposed to swimming-stressed rats. Identical stress protocols did not induce any alteration in atrial sensitivity to catecholamines when the stressed female rats were sacrificed at estrus. We conclude that the stress reaction concerning the mediation of cardiac chronotropism by catecholamines is related to the severity of the stressor agent and is strongly influenced by the estrous cycle.

Ventricular remodeling induced by retinoic acid supplementation in adult rats

Retinoic acid (RA) plays a role in regulating cardiac geometry and function throughout life. The aim of this study was to analyze the cardiac effects of RA in adult rats. Wistar rats were randomly allocated to a control group (n = 18) receiving standard rat chow and a group treated with RA (n = 14) receiving standard rat chow supplemented with RA for 90 days. All animals were evaluated by echocardiography, isolated papillary muscle function, and morphological studies. Whereas the RA-treated group developed an increase in both left ventricular (LV) mass and LV end-diastolic diameter, the ratio of LV wall thickness to LV end-diastolic diameter remained unchanged when compared with the control group. In the isolated papillary muscle preparation, RA treatment decreased the time to peak developed tension and increased the maximum velocity of isometric relengthening, indicating that systolic and diastolic function was improved. Although RA treatment produced an increase in myocyte cross-sectional area, the myocardial collagen volume fraction was similar to controls. Thus our study demonstrates that small physiological doses of RA induce ventricular remodeling resembling compensated volume-overload hypertrophy in rats.

LEFT-VENTRICULAR MASS ESTIMATED BY M-MODE ECHOCARDIOGRAM IS NOT ALTERED BY CHANGES IN CARDIAC SHAPE AND DIMENSIONS DUE TO ACUTE ARTERIAL-HYPERTENSION

The effect of changes in left ventricular (LV) shape and dimensions due to acute arterial hypertension induced by mechanical obstruction of the aorta for 10 min on LV mass values estimated by M-mode echocardiogram was studied in 14 anesthetized dogs. Although the systolic pressure increased from 117.5 +/- 19.9 to 175.4 +/- 22.9 mmHg altered ventricular diameter from 2.77 +/- 0.49 cm to 3.17 +/- 0.67 cm (P<0.05) and wall thickness from 0.83 +/- 0.09 to 0.75 +/- 0.09 cm (P<0.05), LV mass estimated before (73.5 +/- 19.1 g) and after (78.3 +/- 26.4 g) hypertension was not significantly different. We demonstrate here for the first time that changes in LV dimensions induced by acute arterial hypertension do not modify LV mass values estimated by the M-mode electrocardiogram method.

2-DEOXYGLUCOSE-INDUCED FOOD-INTAKE BY NILE TILAPIA, OREOCHROMIS-NILOTICUS (L)

The alimentary and glycemic responses to cytoglycopenia were studied in thirty-one Nile tilapia alevins of indeterminate sex and age, measuring on average 10.67 +/- 0.82 cm. The cytoglycopenia was provoked by ip injection of 60 mg/kg 2-deoxy-D-glucose (2-DG, N = 16). The control group (N = 15) was submitted to ip injection of 0.2 ml saline. Blood samples for glucose determination were obtained before and three hours after drug administration by cardiac puncture. Food was then offered ad libitum. One hour later the animals were sacrificed and their stomachs removed. The difference in wet weight between full and empty stomach was utilized to quantify the food intake. Median food intake was 0.3877 g for the fish treated with 2-DG and 0.107 g for the animals injected with saline. This difference was statistically significant by the Mann-Whitney test (P<0.05). The median values of blood glucose levels before drug injection were 46.19 mg/100 ml in the 2-DG-treated fish and 44.54 mg/100 ml in the control group. Three hours after drug administration, the values were 48.64 mg/100 ml in the experimental group and 56.90 mg/100 ml in the control group. The difference between the values of blood glucose before and after the drug was not significant for either group. We conclude that glucoprivation provokes food intake in fish and that the same glucoprivation was not sufficient to provoke hyperglycemia.

PHARMACOLOGICAL EVALUATION OF THE INHIBITORY EFFECT OF EXTRACTS FROM ANCHIETIA-SALUTARIS ON THE HISTAMINE-RELEASE INDUCED IN THE RAT AND THE GUINEA-PIG

The tea made with leaves and stems of plant Anchietia salutaris is traditionally used in Brazil to treat allergies. We examined the effects of a crude aqueous extract and of purified fractions of this plant on the histamine release induced in rat and guinea pig tissues. The crude extract (3-10 mu g/ml) inhibits the histamine release induced by compound 48/80 (0.5 mu g/ml) and antigen in rat peritoneal mast cells. The inhibition is significant after 10 s of preincubation and is completed after 3 min. The crude extract dissolved in the perfusion fluid (1-30 mu g/ml) also inhibits the histamine release induced in guinea pig heart by cardiac anaphylaxis and in hearts from pretreated animals (10-100 mg/kg i.p.). In pretreated animals, the effect manifests after 3 h, is maximum after 12 h and disappears after 48 h. The histamine release induced in isolated guinea pig heart by ionophore A23187 is inhibited by similar doses as in antigen-induced histamine release. Extraction with solvents concentrated the active principle (s) in the hexane fractions, as demonstrated by the inhibition of the histamine release induced by antigen in isolated cells from guinea pig heart dispersed with collagenase. In subfractions produced by the fractionation of the hexane fraction, the active principle(s) concentrated in the subfractions obtained by extraction with hexane and ethyl acetate, which shows the low polarity of the compound(s). The same subfractions that inhibit the histamine release induced by antigen in cells from guinea pig heart also inhibit pulmonary cells. Our result show that A. salutaris contains low-polarity compound(s) that inhibit the histamine release induced by three different mechanisms in mast cells from two animal species. These facts suggest that the active principle(s) of A, salutaris could be useful in the treatment of allergies and/or as a tool for the study of mast cell secretions.

Myosin heavy chain expression and atrophy in rat skeletal muscle during transition from cardiac hypertrophy to heart failure

The purpose of this investigation was to determine whether changes in myosin heavy chain (MHC) expression and atrophy in rat skeletal muscle are observed during transition from cardiac hypertrophy to chronic heart failure (CHF) induced by aortic stenosis (AS). AS and control animals were studied 12 and 18 weeks after surgery and when overt CHF had developed in AS animals, 28 weeks after the surgery. The following parameters were studied in the soleus muscle: muscle atrophy index (soleus weight/body weight), muscle fibre diameter and frequency and MHC expression. AS animals presented decreases in both MHC1 and type I fibres and increases in both MHC2a and type IIa fibres during late cardiac hypertrophy and CHF. Type IIa fibre atrophy occurred during CHF. In conclusion, our data demonstrate that skeletal muscle phenotype changes occur in both late cardiac hypertrophy and heart failure; this suggests that attention should be given to the fact that skeletal muscle phenotype changes occur prior to overt heart failure symptoms.

Impact of the training program on lipid profile and cardiac health

The aim of this study was to investigate the effects of training programs on serum lipid profile and myocardial oxidative stress. Male Wistar rats (2 mo-old) were divided into three groups (n=8): sedentary (S), loadless trained (T) and trained-overload 2% body weight (TL). T and TL were trained through swimming for 9 weeks. T and TL rats had increased myocardial lipoperoxide (TBA) and lipid hydroperoxide (HP), whereas HP was higher in TL than in T animals. Superoxide dismutase (SOD) activities were lowest in TL. Myocardial glutathione peroxidase (GSH-Px) was lower in TL than in T and S rats. TL decreased HDL-cholesterol and increased LDL-cholesterol. The serum lactate dehydrogenase and TBA were increased, while SOD and GSH-Px activities were decreased in TL rats. Loadless training was able to improve HDL-cholesterol and to reduce LDL-cholesterol. In conclusion, the loadless training program induced beneficial effects on lipid profile, while overload training induced dyslipidemic profile that was associated with serum oxidative stress. The overload training program was deleterious relative to loadless training program, increasing myocardial oxidative stress.

Toxicity of ad lib. overfeeding: effects on cardiac tissue

The aim of the present study was to determine the effects of ad lib, overfeeding and of dietary restriction (DR) on oxidative stress in cardiac tissue. Lipoperoxide concentrations ere decreased and antioxidant enzymes ere increased in moderate-DR-fed rats. Severe-DR induced increased lipoperoxide concentrations. Overfeeding increased lipoperoxide levels in cardiac tissue. Total superoxide dismutase (SOD) and Cu-Zn superoxide dismutase (Cu-Zn SOD) activities were decreased in cardiac tissue at 35 days of overfeeding. As no changes in glutathione peroxidase (GSH-Px) ere observed in overfed rats, awhile SOD and Cu-Zn SOD activities were decreased in these animals. it is assumed that superoxide anion is an important intermediate in the toxicity of ad lib, overfeeding. Overfeeding induced alterations in markers of oxidative stress in cardiac tissue. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

Corrosion protection of stainless steel by polysiloxane hybrid coatings prepared using the sol-gel process

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Comparative study between atropine and hyoscine-N-butylbromide for reversal of detomidine induced bradycardia in horses

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

TEGDMA-induced oxidative DNA damage and activation of ATM and MAP kinases

The development of strategies for the protection of oral tissues against the adverse effects of resin monomers is primarily based on the elucidation of underlying molecular mechanisms. The generation of reactive oxygen species beyond the capacity of a balanced redox regulation in cells is probably a cause of cell damage. This study was designed to investigate oxidative DNA damage, the activation of ATM, a reporter of DNA damage, and redox-sensitive signal transduction through mitogen-activated protein kinases (MAPKs) by the monomer triethylene glycol dimethacrylate (TEGDMA). TEGDMA concentrations as high as 3-5 mm decreased THP-1 cell viability after a 24 h and 48 h exposure, and levels of 8-oxoguanine (8-oxoG) increased about 3- to 5-fold. The cells were partially protected from toxicity in the presence of N-acetylcysteine (NAC). TEGDMA also induced a delay in the cell cycle. The number of THP-1 cells increased about 2-fold in G1 phase and 5-fold in G2 phase in cultures treated with 3-5 mm TEGDMA. ATM was activated in THP-1 cells by TEGDMA. Likewise, the amounts of phospho-p38 were increased about 3-fold by 3 mm TEGDMA compared to untreated controls after a 24 h and 48 h exposure period, and phospho-ERK1/2 was induced in a very similar way. The activation of both MAPKs was inhibited by NAC. Our findings suggest that the activation of various signal transduction pathways is related to oxidative stress caused by a resin monomer. Signaling through ATM indicates oxidative DNA damage and the activation of MAPK pathways indicates oxidative stress-induced regulation of cell survival and apoptosis. (C) 2008 Elsevier Ltd. All rights reserved.

Cardiorespiratory and neuroendocrine changes induced by methadone in conscious and in isoflurane anaesthetised dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)