Ultrasound-microwave-assisted extraction of polyphenolic compounds from Mexican "Ataulfo" mango peels: Antioxidant potential and identification by HPLC/ESI/MS.

INTRODUCTION: Mango is used in traditional medicine in many countries. However, the processing by-products are not currently used and generate large pollution problems and high handling costs. OBJECTIVE: To study the effect of different parameters in the extraction of polyphenolic compounds from mango peels using modern and ecological ultrasound-microwave-assisted extraction technology. METHODOLOGY: Various parameters of these processes were studied: the extract was recovered by liquid chromatography using Ambetlite XAD-16. The total polyphenol content was determined by Folin-Ciocalteu's and HCl-butanol methods. Antioxidant activity was determined by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS+), 1,10-diphenyl-2-20-picrylhydrazyl (DPPH), and lipid oxidation inhibition methods. The recovered compounds were identified by high-performance liquid chromatography-mass spectrometry (HPLC-MS). RESULTS: The best extraction conditions were solid/liquid ratio of 1/5 g/mL, ethanol percentage of 50%, and an extraction time of 10 min. Under these conditions, the total polyphenol content was 54.15 mg/g, and the antioxidant activities were greater than 90% inhibition in the three assays evaluated. According to the high-performance liquid chromatography/electrospray ionization/mass spectrometry (HPLC/ESI/MS) analysis, nine polyphenolic compounds were identified; most of them were gallotannins, such as pentagalloyl glucose. CONCLUSION: Ultrasound-microwave-assisted extraction was shown to be effective and allowed the recovery of antioxidant polyphenolic compounds. The results indicated that mango peel extracts can be used as natural antioxidant components in the pharmaceutical and functional food industries.

Bacterial resistance and failure of clinical cure could be produced by oxidative stress in patients with diabetes or cardiovascular diseases during fluoroquinolone therapy.

Fluoroquinolone agents are used widely for the treatment of infectious diseases which are a common cause of deaths around the world. The level of oxidative stress in patients taking fluoroquinolone antibiotics has not been considered a factor to reduce the clinical efficacy of this kind of drugs. Patients with diabetes and/or cardiovascular diseases present abnormal levels of oxidative stress in the blood stream. In this regards, our hypothesis supposes that patients with diabetes and/or cardiovascular disease suffering a bacterial disease could experience a therapeutic failure and bacterial resistance when treated with fluoroquinolones. The crucial mechanism could be an inefficient blood distribution of the drug via red blood cell dysfunction induced by oxidative stress that might reduce the pharmacokinetic-pharmacodinamic ratios. In this way, we review the scientific information to support our hypothesis alongside possible implications. Additionally, this work exhibits the urgent need of studies considering these conditions for quinolone agents.

Further analysis of the inhibition by agmatine on the cardiac sympathetic outflow: Role of the α2-adrenoceptor subtypes.

This study has investigated the role of the α2-adrenoceptor subtypes involved in the inhibition of the cardiac sympathetic outflow induced by intravenous (i.v) infusions of agmatine. Therefore, we analysed the effect of an i.v. bolus injections of the selective antagonists BRL 44408 (300µg/kg; α2A), imiloxan (3000µg/kg; α2B), and JP-1302 (300µg/kg; α2C) given separately, and their combinations: BRL 44408 plus Imiloxan, JP 1302 plus imiloxan, BRL 44408 plus JP-1302, BRL 44408 plus imiloxan plus JP-1302 on the cardiac sympatho-inhibition of agmatine. Also, the effect of the combination BRL 44408 plus JP-1302 plus AGN 192403 (3000µg/kg; I1 antagonist) was evaluated. In this way, i.v. infusions of 1000µg/kg min of agmatine, but not 300, inhibited the tachycardic response induced by electrical stimulation. Furthermore, the antagonists used or their combinations had no effect on the electrically-induced tachycardic response. On the other hand, the inhibitory response of agmatine was: (1) partially antagonized by BRL 44408 or JP-1302 given separately, a similar response was observed when we administered their combination with imiloxan, but not by imiloxan alone, (2) antagonized in greater magnitude by the combination BRL 44408 plus JP-1302 or the combination BRL 44408 plus imiloxan plus JP-1302, and (3) abolished by the combination BRL 44408 plus JP-1302 plus AGN 192403. Taken together, these results demonstrate that the α2A- and α2C-adrenoceptor subtypes and I1-imidazoline receptors are involved in the inhibition of the cardiac sympathetic outflow induced by agmatine.

Oxidative stress and metabolic syndrome: cause or consequence of Alzheimer's disease?

Alzheimer's disease (AD) is a major neurodegenerative disease affecting the elderly. Clinically, it is characterized by a progressive loss of memory and cognitive function. Neuropathologically, it is characterized by the presence of extracellular ß-amyloid (Aß) deposited as neuritic plaques (NP) and neurofibrillary tangles (NFT) made of abnormal and hyperphosphorylated tau protein. These lesions are capable of generating the neuronal damage that leads to cell death and cognitive failure through the generation of reactive oxygen species (ROS). Evidence indicates the critical role of Aß metabolism in prompting the oxidative stress observed in AD patients. However, it has also been proposed that oxidative damage precedes the onset of clinical and pathological AD symptoms, including amyloid-ß deposition, neurofibrillary tangle formation, vascular malfunction, metabolic syndrome, and cognitive decline. This paper provides a brief description of the three main proteins associated with the development of the disease (Aß, tau, and ApoE) and describes their role in the generation of oxidative stress. Finally, we describe the mitochondrial alterations that are generated by Aß and examine the relationship of vascular damage which is a potential prognostic tool of metabolic syndrome. In addition, new therapeutic approaches targeting ROS sources and metabolic support were reported.

Hindlimb claudication reflects impaired nitric oxide-dependent revascularization after ischemia.

Although vascular remodeling is important in preventing tissue damage and restoring muscle function, there is no evidence of a relationship between vascular remodeling and muscle function after peripheral vascular occlusion. Nitric oxide (NO) has been implicated in the process of vascular remodeling in hindlimb ischemia. Thus, development of alterations in hindlimb gait after ischemia may be associated with impaired nitric oxide-dependent, vascular blood flow recovery. We evaluated hindlimb gait as an index of ischemia-induced revascularization and tested the effects of NO synthase inhibition on both hindlimb blood flow and hindlimb gait locomotion. After 14 days of ischemia, the ischemic hindlimb showed no significant differences in gait locomotion compared to the sham-operated hindlimb. However, hindlimb ischemia drastically reduced hindlimb blood flow from 46+/-3 mL/min/100 g to 12+/-2 mL/min/100 g which reverted to 33+/-5 mL/min/100 g after 14 days of ischemia. eNOS mRNA expression levels at 3, 7, 14, and 28 days after initiation of ischemia, were increased by 50+/-5%, 100+/-10%, 140+/-8% and 270+/-12% respectively and eNOS protein expression levels at 7, 14, and 28 days, were increased by 28+/-3%, 62+/-6% and 80+/-16% respectively. However, eNOS inhibition caused by l-NAME treatment prevented blood flow recovery and correction of abnormal gait locomotion in rats. Thus, the duration of the stride-swing phase increased and the stride length decreased. The knee joint angle decreased during flexion and extension with eNOS inhibition. In conclusion, ischemia-induced revascularization is associated with recovery of both hindlimb blood flow and normal gait locomotion. Moreover, prevention of NO synthesis, a key messenger in ischemia-induced revascularization, is associated with impairment in hindlimb locomotion. Thus, gait locomotion represents a functional model that could be used to evaluate the degree of ischemia-induced revascularization.

The role of nitric oxide in the post-ischemic revascularization process.

Following arterial occlusion, blood vessels respond by sprouting new capillaries (i.e. angiogenesis) and by growing and remodelling pre-existing arterioles into physiologically relevant arteries (i.e. arteriogenesis). The importance of nitric oxide (NO) in ischemia-induced angiogenesis is supported by 4 main findings: (i) the ischemic limb shows an increase in endothelial nitric oxide synthase (eNOS) mRNA, protein expression and NO synthesis; (ii) the absence of the NO pathway (by either pharmacological inhibition or gene disruption of eNOS) abolishes ischemia-induced angiogenesis; (iii) supplementation of NO by the use of exogenous sources restores ischemia-induced angiogenesis; and (iv) cardiovascular diseases associated with decreased NO synthesis show impaired ischemia-induced angiogenesis. Thus, impairment of the NO metabolic pathway could be one of the main contributing factors for the development of peripheral arterial occlusive disease. The restoration of normal NO levels in diseased arteries is therefore a major therapeutic goal; this could be achieved by supplementation with exogenous NO or by strategies designed to increase the concentration of endogenous NO.