59 research outputs found
The treatment of hyperuricemia.
AbstractHyperuricemia has long been established as the major etiologic factor in gout. Alongside with an inflammatory state triggered by urate crystal deposition in the joints, hyperuricemia displayed additional pathophysiological consequences leading to tissue inflammation mainly in the vascular wall. Thus, therapeutic strategies used to treat hyperuricemia in the past decades have often been focused on limiting acute episodes. Recently, evidence has been accumulated suggesting that chronic urate deposition requires a correct treatment not limited to acute episodes based on the modulation of the activity of key enzymes involved in metabolism and excretion of urate including xanthine oxidoreductase (XO) and URAT1. The present review article will try to summarize the most recent evidences on the efficacy of XO inhibitors and uricosuric compounds in lowering uric acid levels in both the bloodstream and peripheral tissues. In particular, we will focus on the effect of novel XO inhibitors in counteracting uric acid overproduction. On the other hand, the effect of lowering uric acid levels via XO inhibition will be correlated with attenuation oxidative stress which leads to endothelial dysfunction thereby contributing to the pathophysiology of diabetes, hypertension, arteriosclerosis, and chronic heart failure. Hence, scavenging and prevention of the XO generated oxygen radical accumulation emerge as an intriguing novel treatment option to counteract uric acid-induced tissue damages
Imbalance of thalamic metabolites in an experimental model of hypertension: role of bergamot polyphenols
Cerebral metabolites are associated with different physiological and pathological processes in brain tissue. Among them, the concentrations of N-acetylaspartate (NAA) and choline-containing compounds (Cho) in the thalamic region are recognized and analyzed as important predictive markers of brain impairment. The relationship among hypertension, modulation of brain metabolite levels and cerebral diseases is of recent investigation, leaving many unanswered questions regarding the origin and consequences of the metabolic damage caused in grey and white matter during hypertension. Here we provide evidence for the influence of hypertension on NAA and Cho ratios in hypertensive rat thalamus and how the use of natural occurring compounds ameliorates the balance of thalamic metabolites
Megestrol acetate improves cardiac function in a model of cancer cachexia- induced cardiomyopathy by autophagic modulation
Background Cachexia is a complex metabolic syndrome associated with cancer.
One of the features of cachexia is the loss of muscle mass, characterized by
an imbalance between protein synthesis and protein degradation. Muscle atrophy
is caused by the hyperactivation of some of the main cellular catabolic
pathways, including autophagy. Cachexia also affects the cardiac muscle. As a
consequence of the atrophy of the heart, cardiac function is impaired and
mortality is increased. Anti-cachectic therapy in patients with cancer
cachexia is so far limited to nutritional support and anabolic steroids. The
use of the appetite stimulant megestrol acetate (MA) has been discussed as a
treatment for cachexia. Methods In this study the effects of MA were tested in
cachectic tumour-bearing rats (Yoshida AH-130 ascites hepatoma). Rats were
treated daily with 100 mg/kg of MA or placebo starting one day after tumour
inoculation, and for a period of 16 days. Body weight and body composition
were assessed at baseline and at the end of the study. Cardiac function was
analysed by echocardiography at baseline and at day 11. Locomotor activity and
food intake were assessed before tumour inoculation and at day 11. Autophagic
markers were assessed in gastrocnemius muscle and heart by western blot
analysis. Results Treatment with 100 mg/kg/day MA significantly attenuated the
loss of body weight (−9 ± 12%, P < 0.05) and the wasting of lean and fat mass
(−7.0 ± 6% and −22.4 ± 3 %, P < 0.001 and P < 0.05, respectively).
Administration of 100 mg/kg/day MA significantly protected the heart from
general atrophy (633.8 ± 30 mg vs. placebo 474 ± 13 mg, P < 0.001). Tumour-
bearing rats displayed cardiac dysfunction, as indicated by the significant
impairment of the left ventricular ejection fraction, the left ventricular
fractional shortening, the stroke volume, the end dyastolic volume, and the
end systolic volume. In contrast, MA significantly improved left ventricular
ejection fraction, left ventricular fractional shortening, and left
ventricular end systolic volume. Western blotting analysis showed an
upregulation of the autophagic pathway in the gastrocnemius and hearts of the
placebo-treated tumour-bearing rats. Treatment with MA, however, was able to
modulate the autophagic markers (e.g. Beclin-1, p62, TRAF6, and LC3) in the
gastrocnemius and in the hearts of tumour-bearing rats. Most importantly, 100
mg/kg/day MA reduced mortality [hazard ratio (HR): 0.44; 95%CI: 0.20–1.00; P =
0.0486]. Conclusions Megestrol acetate improved survival and reduced wasting
through a marked downregulation of autophagy, occurring in both skeletal and
heart muscle, the latter effect leading to a significant improvement of
cardiac function. Our data suggest that MA might represent a valuable strategy
to counteract the development of cancer cachexia-induced cardiomyopathy
Posttranslational Nitration of Tyrosine Residues Modulates Glutamate Transmission and Contributes to N-Methyl-D-aspartate-Mediated Thermal Hyperalgesia
The Effect of Bergamot-Derived Polyphenolic Fraction on LDL Small Dense Particles and Non Alcoholic Fatty Liver Disease in Patients with Metabolic Syndrome
The occurrence of Metabolic Syndrome (MS) represents an independent risk factor for developing cardiovascular disease states in patients suffering from type 2 diabetes mellitus. Moreover, both the size of LDL particles and liver dysfunction identified as non alcoholic fatty liver disease (NAFLD) represent important biomarkers for the development of cardiometabolic risk in patients with MS. Here we studied the effect of bergamot polyphenolic fraction (BPF) in patients with MS and NAFLD. 107 patients were enrolled at the San Raffaele IRCCS (Rome). All of them showed ultrasonografic evidences of NAFLD and at least three out of five previous identified criteria for the diagnosis of MS. Patients were divided into two groups: one receiving placebo and the second receiving BPF 650 mg twice a day for 120 consecutive days. In the group receiving BPF 650 mg twice a day, a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides alongside with an increase of HDL cholesterol was found. This effect was accompanied by significant reduction of both ultrasonographic and metabolic biomarkers of NAFLD. Moreover, a significant reduction of small dense LDL particles, as detected via proton NMR Spectroscopy, was found after BPF treatment. In conclusion, our data confirm the beneficial effect of bergamot-extract in patients with MS an effect highlighted by significant reduction of small dense LDL particles and by improvement of NAFLD biomarkers. This suggests a potential preventive role of bergamot derivatives in reducing cardiometabolic risk
Amyloid β peptide-induced inhibition of endothelial nitric oxide production involves oxidative stress-mediated constitutive eNOS/HSP90 interaction and disruption of agonist-mediated Akt activation
Modulation of RAAS-natriuretic peptides in the treatment of HF: Old guys and newcomers
The use of renin–angiotensin–aldosterone system (RAAS) inhibitors in the treatment of chronic heart failure (HF) and arterial hypertension is recommended by the European Society of Cardiology Guidelines on the basis of consolidated evidence supporting their efficacy in the development of such a disease. However, the high incidence of re-hospitalization and mortality in patients undergoing chronic HF, leads to the need for the development of novel RAAS inhibitors possessing a better pharmacokinetic/pharmacodynamics profile in approaching hemodynamic imbalance and myocardial dysfunction associated with the development of chronic HF. Here we summarize some of the recent advances in the area of RAAS-modulators, including novel renin inhibitors, mineralcorticoid receptor antagonists and novel AT1 and AT2-receptor modulators. In addition, the pharmacology of a new class of compounds which display both AT1-receptor blocking properties combined with inhibition of neprilysin, the vasopeptidase enzyme degradating natriuretic peptide (ARNi), will be reviewed, alongside with their impact in the pathophysiology of chronic HF
Bergamot polyphenolic fraction counteracts photoageing in human keratinocytes
Photoageing represents the addition of extrinsic chronic ultraviolet radiation induced damage on intrinsic aging and accounts for most age-associated changes in skin appearance. The skin contains numerous endogenous antioxidants to help provide protection from reactive oxidative species generated during normal cellular metabolism. However, overexposure to UV radiation can lead to a significant reduction in the antioxidant supply accompanied by an increase of proinflammatory cytokines leading to accelerated oxidative damage. Photochemoprevention with botanical antioxidants is a strategy shown to be capable of blunting the damaging effects of ultraviolet radiation.
Together with antioxidant properties, dietary flavonoids and their metabolites may modulate basic cellular signal transduction pathways leading to anti-proliferative, anti-aging and immune modulating responses. Here, we describe the effects of bergamot polyphenolic fraction (38% BPF), a highly concentrated extract of flavonoids derived from the citrus bergamot fruit, able to inhibit UVB mediated decrease in cell viability, overexpression of inflammatory cytokine biomarker interleukin-1beta (IL-1β), telomere shortening and decreases in telomerase activity
Cachrys L. Genus: A Comprehensive Review on Botany, Phytochemistry and Biological Properties
The Cachrys L. genus belongs to the Apiaceae family and it is widely distributed in the Mediterranean basin, with plant species being endemic to southern Europe, Asia, and northern Africa. Different studies, focused on the phytochemical composition of Cachrys spp. and the biological properties of their phytocomplexes, have been reported. These works mostly focused on the essential oils obtained from these plants, and pointed out that Cachrys species are a rich source of coumarins, mainly furanocoumarins. Other phytochemicals, such as terpenes, fatty acids, phytosterols, and flavonoids have been also identified. Moreover, a number of biological properties such as antioxidant, antimicrobial, anti-inflammatory, cytotoxic, and photocytotoxic effects have been assessed. Nevertheless, a review of the chemical and pharmacological properties of this genus is not available in the literature. The aim of this paper is to provide an overview of the reports concerning the identified phytochemicals and the biological effects reported for Cachrys spp., and to offer a comprehensive understanding of the potential of this genus as a source of bioactive compounds. The current taxonomy, the traditional uses, and the toxicological aspects of plants belonging to this genus are also reported, and the future research directions are discussed
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