This work was performed to study the effect of allicin on hypertension and cardiac function in a rat model of CKD. The groups were control, CKD (5/6 nephrectomy), and CKD-allicin treated (CKDA) (40 mg/kg day/p.o.). Blood pressure was monitored (weekly/6 weeks). The cardiac function, vascular response to angiotensin II, oxidative stress, and heart morphometric parameters were determined. The CKD group showed hypertension and proteinuria. The coronary perfusion and left ventricular pressures were decreased in CKD group. In contrast, the vascular response to angiotensin II and expression of angiotensin II type 1 receptor (AT1R) were increased. These data were associated with the increment in morphometric parameters (weight of heart and left ventricle, heart/BW and left ventricular mass index, and wall thickness). Concurrently, the oxidative stress was increased and correlated inversely with the expression of Nrf2, Keap1, and antioxidant enzymes Nrf2-regulated. Allicin treatment attenuated hypertension and improved the renal and the cardiac dysfunctions; furthermore, it decreased the vascular reactivity to angiotensin II, AT1R overexpression, and preserved morphometric parameters. Allicin also downregulated Keap1 and increased Nrf2 expression, upregulated the antioxidant enzymes, and reduced oxidative stress. In conclusion, allicin showed an antihypertensive, nephroprotective, cardioprotective, and antioxidant effects, likely through downregulation of AT1R and Keap1 expression.

No abstract

Myocardial ischemia continues to be the first cause of morbimortality in the world; the definitive treatment is reperfusion; however, this action causes additional damage to ischemic myocardial tissue; this forces to seek therapies of cardioprotection to reduce this additional damage. There are many cardioprotective agents; within these, cannabinoids have shown to have beneficial effects, mainly cannabidiol (CBD). CBD is a non psychoactive cannabinoid. To evaluate the effect in experimental models of CBD in myocardial ischemia reperfusion in rats, twelve‐week‐old male rats have been used. The animals were divides in 3 groups: control(C), ischemia reperfusion (IR) and CBD pretreatment (1/day/5mg/kg /10days). Langendorff organ isolate studies were performed, and the area of infarction was assessed with triphenyl tetrazolium, in addition to molecular analysis of AT1 and AT2 receptors and Akt and Erk proteins and their phosphorylated forms related to RISK pathways. It was observed that there is an improvement with the use of CBD increasing inotropism and cardiac lusitropism, improving considerably the cardiovascular functionality. These could be related to the reduction of the area of infarction and activation of the AT2 receptor and the RISK pathway with absence of activation of the AT2 receptor (these could relate the reduction of the infarct area and the restoration of cardiovascular function with the activation of the AT2 receptor and the RISK pathway with the absence of activation of the AT2 receptor). The use of cannabinoids was shown to have beneficial effects when used as a treatment for myocardial reperfusion damage.

Several of the luminal endothelial glycocalyx functions are exerted via interactions with glycosidic components and sugar binding proteins with lectinic activity. One important example is the mannose receptor (MR). The MR has been detected in cell types that mediate the phagocytosis and pinocytosis of particles and solutes containing mannose. Using isolated constant pressurized rat mesenteric arteries (RMA), we evaluated the effects of a mannose polymer in the vascular tone. RMA were pre-contracted with 10 micromol/L phenylephrine and carbohydrates were perfused at 20 microliters/min. Perfusion of free D-mannose (1 nmol/L to 100 micromol/L) induced a concentration-dependent vasodilation of pre-contracted RMA. Perfusion of mannose polymer (1 nmol/L to 100 micromol/L) induced a larger effect in a concentration-dependent vasodilation. Mannose polymer's maximum effect reached a 96 percent of basal diameter; this significant vasodilation was not nitric oxide (NO) or cyclooxygenase (COX) dependent effect. We corroborated the binding of the mannose polymer to the endothelial lumen, by perfusion of a fluorescently labeled mannose polymer; and also, we detected a significant level of MR mRNA in whole mesenteric arteries. With all these, we proposed a novel effect of a MR in the regulation of vascular tone.

Abstract:In Mexico, medicinal plants are widely used. The use of Randia aculeata by healers against snakebites has never been scientifically tested in relation to possible effects on blood parameters and muscle tissue damage. Interviews were carried out in Jamapa, Veracuz, Mexico, with local residents to collect information about the traditional use of Randia aculeata. In this locality, seven pieces of fruit from the plant are mixed in a liter of alcohol, and then administered orally against snakebites. By using histological techniques and a murine model, we explored its cytoprotective properties against the effects of Crotalus simus and Bothrops asper venoms. Possible protections provided by the plant against tissue damage to skeletal and cardiac muscles and against the typical loss of red blood cells were analyzed. Randia aculeata caused an increase in microhematocrit and total hemoglobin, parameters that are often decremented in association with the loss of red blood cells, which is a characteristic effect of animal venom. Randia aculeata was also shown to protect against the lowering of platelet levels caused by Bothrops asper venom. Finally, Randia aculeata produced a partial inhibition of necrosis following administration of snake venom in skeletal and myocardial muscles. The present results provide solid evidence for the traditional use of Randia aculeata against snakebites, as demonstrated by protection against muscular tissue damage and the diminution of red blood cells.Key words: Rubiaceae, antivenoms, Bothrops, Crotalus, cytoprotection. Original PaPer INTRODUCTIONOphidian accidents represent a serious health problem, as they lead to an estimated 50,000 deaths and another 22,000 permanent injuries, including amputations and other losses of bodily functions that impede proper development within society (1). Among medical treatments for such accidents, medicinal plants used as ophidian antidotes generate special interest because of their potential pharmacological use. However, information remains scarce and many cases have not been subjected to true scientific analysis.In Mexico, a few plants have been evaluated including Brongniartia podalyrioides and B. intermedia, which were found to contain edunol, a substance that neutralizes the cardiological and toxic effects of the Bothrops atrox venom (2). In the country there are snakebite healers called "culebreros" that claim to know the proper antiophidic herbal remedies and methods of application (3). These healers often represent the only alternative given the lack of medical services that could otherwise provide anti-ophidian serum based on scientific research. In the best of cases, such a healer is apprenticed based on generations of practice that has led to an accumulation of knowledge on the effectiveness of distinct medicinal plants. A healer with this background is in reality keeping a valuable tradition alive (4). However, information on this use of medicinal plants is scarce and in many cases lacks scientific analysis.Ethnobotanic study of Randia ...

The study of serum levels of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES and CXCL8/IL-8 chemokines in epithelial ovarian cancer patients identified a down-regulation in CCL2/MCP-1 and CCL4/MIP-1β, which suggests that the two chemokines may play an important role in the pathophysiology of ovarian cancer.

Oxidative stress is involved in the development of diabetes. Nitric oxide (NO) contributes to oxidative stress, affects the synthesis of glutathione (GSH) in tissues and also regulates important physiological processes. The levels of nitrosative stress, assessed by measuring the levels of 3-nitrotirosina (3NT) as well as the bioavailability of NO are modulated by exercise and hyperbaric oxygenation (HBO). The aim of the present study was to evaluate the effects of exercise and HBO on the levels of NO, 3NT and GSH in tissues of various organs obtained from diabetic mice. Female mice were fed a high-fat/high-fructose diet to induce diabetes. Mice with diabetes were subjected to exercise and/or HBO. Initial and final concentrations of NO, 3NT and GSH were assessed in the muscle, liver, kidney, heart, spleen, lung, brain, visceral adipose, thoracic aorta and small intestine. Diabetes did not affect initial values of NO, although it significantly increased the levels of 3NT. The basal level of GSH in the diabetic group was lower than or comparable to that of the control group in the majority of the organs assessed. A negative correlation was observed between 3NT and GSH levels in the initial values of all tissues of the control group only, whereas all pathological tissues showed a positive correlation between NO and GSH. There was an increase or a stabilization of GSH levels in the majority of the organs in all treated mice despite the increase in nitrosative stress.

Prostanoids are involved in the phenylephrine-induced contraction of the aorta. Here, we examined whether or not constitutive cyclooxygenase-2 (phosholipases C and A2) is the source of prostanoids in the smooth muscle of the arterial wall of the thoracic and abdominal aorta. Both cyclooxygenase isoforms (COX-1 and COX-2) were expressed in the two aortic segments, but their expression was not altered by phenylephrine, the protein synthesis inhibitor cycloheximide, or the phospholipase A2 inhibitors arachidonyl trifluoromethyl ketone and methyl arachidonyl fluorophosponate. Indomethacin and NS398, which are a non-selective and selective COX-2 inhibitor, respectively, but not SC-560, which is a COX-1-selective inhibitor, inhibited the effect of phenylephrine on the abdominal, but not the thoracic, aorta. Similarly, U73122, which is a phospholipase C inhibitor, and RHC80267, which is a diacylglycerol lipase inhibitor, inhibited the effect of phenylephrine. These findings suggest that prostanoids, which are produced by constitutively active COX-2, influence the contractile response of the abdominal aorta and that the production of arachidonic acid relies on phospholipase C and diacylglycerol lipase.