RESUMO
To investigate the aetiology of chronic idiopathic axonal polyneuropathy (CIAP), 50 consecutive patients were compared with 50 control subjects from the same region. There were 22 patients with painful neuropathy and 28 without pain, 26 with sensory neuropathy and 24 with sensory and motor neuropathy. The typical picture was a gradually progressive sensory or sensory and motor neuropathy. It caused mild or sometimes moderate disability, and reduced the quality of life. There was no evidence that alcohol, venous insufficiency, arterial disease or antibodies to peripheral nerve antigens played a significant part. There was a possible history of peripheral neuropathy in the first or second-degree relatives of six patients and no controls (P = 0.01), and claw toes were present in 12 patients and four controls (P = 0.03). Thirty-two per cent of the patients and 14% of the controls had impaired glucose tolerance or fasting hyperglycaemia but, after adjusting for age and sex, the difference was not significant (P = 0.45), even in the painful neuropathy subgroup. The mean (SD) fasting insulin concentrations were significantly (P = 0.01) higher in the patients [75.9 (44.4) mmol/l] than the controls [47.3 (37.9) mmol/l], and the mean was higher still in the painful neuropathy subgroup [92.2 (37.1) mmol/l] (P < 0.0001). However, insulin resistance as assessed using the homeostasis model assessment formula was not significantly greater in the patients, even in those with pain, than the controls. After adjustment for body mass index as well as age and sex, there was no significant difference in the serum cholesterol concentrations, but there were significantly higher triglyceride concentrations in the patients [mean 1.90 (1.41) mmol/l] than the controls [mean 1.25 (0.79] mmol/l) (P = 0.02). In the patients with painful peripheral neuropathy, the mean triglyceride concentration was 2.37 (1.72), which was even more significantly greater compared with the controls (P = 0.003). In conclusion, CIAP is a heterogeneous condition. A logistic regression analysis identified environmental toxin exposure and hypertriglyceridaemia, but not glucose intolerance or alcohol overuse as significant risk factors that deserve further investigation as possible causes of CIAP.
Assuntos
Polineuropatias/etiologia , Idoso , Antropometria , Ácido Ascórbico/sangue , Autoanticorpos/sangue , Estudos de Casos e Controles , Avaliação da Deficiência , Feminino , Intolerância à Glucose/complicações , Substâncias Perigosas/toxicidade , Humanos , Hipertrigliceridemia/complicações , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Polineuropatias/genética , Polineuropatias/fisiopatologia , Qualidade de Vida , Fatores de Risco , Vitamina E/sangueRESUMO
The purpose of this study was to investigate the absorption and metabolism of hydroxycinnamates from artichoke extract by determining the urinary excretion of the conjugates. Ten healthy, non smoking volunteers (5 female, 5 male) were given three capsules containing artichoke extract every 4 h (0, 4, 8 h) following two days of a low-polyphenol diet. One capsule contained 320 mg of artichoke extract equivalent to 34.3 +/- 0.6 mg/g hydroxycinnamates (caffeic acid derivatives) and 5.6 +/- 0.1 mg/g flavonoids. Polyphenols and phenolic acids present in the artichoke extract were not detected in the urine either as conjugates or aglycones. However, ferulic, isoferulic, dihydroferulic and vanillic acid were identified as major metabolites after beta-glucuronidase treatment of urine. The amount excreted as well as the ratio to that of creatinine, a biomarker for the general excretion rate, increased significantly on the study day compared to the pre-supplementation day. Thus, the caffeic acid esters found in the artichoke extract capsule are absorbed, metabolised and excreted as methylated phenolic acids such as ferulic, isoferulic, dihydroferulic and vanillic acid.
Assuntos
Ácidos Cafeicos/química , Ácidos Cafeicos/metabolismo , Hidroxibenzoatos/metabolismo , Verduras/química , Adulto , Disponibilidade Biológica , Ácidos Cafeicos/administração & dosagem , Ácidos Cafeicos/farmacocinética , Cromatografia Líquida de Alta Pressão , Ácidos Cumáricos/metabolismo , Ácidos Cumáricos/farmacocinética , Ácidos Cumáricos/urina , Creatinina/metabolismo , Creatinina/urina , Dieta , Feminino , Suco Gástrico/metabolismo , Humanos , Hidroxibenzoatos/farmacocinética , Hidroxibenzoatos/urina , Masculino , Ácido Vanílico/metabolismo , Ácido Vanílico/urinaRESUMO
There is considerable interest in the bioavailability of flavonoids and phenolic components of the diet and their bioactivity in vivo. However, little is known of pre-absorption events in the gastric lumen. The effects of the acidic environment, as found in the gastric milieu, on procyanidin oligomers of catechin polyphenols has been investigated. The results show that under these conditions the procyanidin oligomers (trimer to hexamer) are hydrolysed to mixtures of epicatechin monomer and dimer, thus enhancing the potential for their absorption in the small intestine.
Assuntos
Biflavonoides , Cacau/química , Catequina/farmacocinética , Suco Gástrico/metabolismo , Proantocianidinas , Disponibilidade Biológica , Catequina/química , Cromatografia Líquida de Alta Pressão , Humanos , Concentração de Íons de Hidrogênio , Íleo/metabolismo , Técnicas In Vitro , Absorção Intestinal , Jejuno/metabolismoRESUMO
Iron chelators can reduce radical damage inflicted on cells by two mechanisms, either direct scavenging of the radicals or by scavenging loosely bound iron which under aerobic conditions can generate radicals. Frequently it is not possible to distinguish between these two modes of action. 3-Hydroxypyridin-4-ones, in contrast to many iron(III) chelators are poor radical scavengers and therefore have potential in analysing mechanisms involved in biochemical and physiological processes which are centered on radical-induced cell injury.
Assuntos
Compostos Férricos/metabolismo , Sequestradores de Radicais Livres/farmacologia , Quelantes de Ferro/farmacologia , Picratos , Bepridil/análogos & derivados , Bepridil/farmacologia , Compostos de Bifenilo , Relação Dose-Resposta a Droga , Sequestradores de Radicais Livres/química , Hidroxiureia/farmacologia , Quelantes de Ferro/química , Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Peroxynitrite is a cytotoxic species generated by the reaction between superoxide and nitric oxide. In this study the ability of hydroxycinnamate antioxidants to decrease peroxynitrite-mediated nitration of tyrosine was investigated. The results obtained show that all compounds were able to inhibit nitration of tyrosine. The potency of inhibitory activity was in the order; caffeic acid > or = chlorogenic acid > or = ferulic acid > p-coumaric acid > ocoumaric acid > m-coumaric acid. Trolox, which was included in the study for comparative purposes, had an activity between that of ferulic acid and p-coumaric acid. The data obtained suggest that hydroxycinnamates can act by one of two possible mechanisms: preferential nitration for monophenolates and electron donation by catecholates.
Assuntos
Antioxidantes/farmacologia , Ácidos Cumáricos/farmacologia , Sequestradores de Radicais Livres , Nitratos/química , Nitratos/farmacologia , Tirosina/química , Ácidos Cafeicos/farmacologia , Ácido Clorogênico/farmacologia , Cromanos/farmacologia , Cromatografia Líquida de Alta Pressão , Radicais Livres , Espectrofotometria , Tirosina/análogos & derivadosRESUMO
Peroxynitrite is a powerful oxidising and nitrating agent generated in vivo by the combination of nitric oxide and superoxide. Previous studies have shown that on exposure to peroxynitrite, low density lipoprotein (LDL) is modified resulting in both a time- and concentration-dependent change to lipid and protein components. The present investigation highlights the reaction between carotenoids and tocopherols, present within the lipophilic phase of LDL, and peroxynitrite at varying concentrations. It was observed that the carotenoids were consumed by a significantly greater proportion than that of the tocopherols with lycopene (87.2 +/- 11%) being more reactive than beta-carotene (68.2 +/- 5.8%) when exposed to peroxynitrite (50 microM) for 1 min. Among the tocopherols, alpha-tocopherol (54.9 +/- 20.2%) was more extensively depleted than gamma-tocopherol (14.7 +/- 1.09%) at peroxynitrite concentration of 500 microM. It was also observed that peroxynitrite, unlike copper ions, does not lead to significant peroxidation of LDL as determined by the formation of conjugated dienes and thiobarbituric acid-reactive substances.
Assuntos
Carotenoides/metabolismo , Lipoproteínas LDL/metabolismo , Nitratos/metabolismo , Vitamina E/metabolismo , Cobre/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Licopeno , Estrutura Molecular , Oxirredução , Quinonas/metabolismo , beta Caroteno/metabolismoRESUMO
Peroxynitrite is a cytotoxic species generated by the reaction between superoxide and nitric oxide. The ability of catechins and their gallate esters to decrease peroxynitrite-induced nitration of tyrosine and to limit surface charge alteration of low density lipoprotein (LDL) was investigated. All compounds tested were found to be potent peroxynitrite scavengers preventing the nitration of tyrosine. The ability of the catechin polyphenols at 10 microM to minimise tyrosine nitration induced by peroxynitrite (500 microM) was ECG (38.1 +/- 3.6%) approximately EGCG (32.1 +/- 7.5%) approximately gallic acid (32.1 +/- 1.9%) > catechin (23.9 +/- 5.4%) approximately epicatechin (22.9 +/- 3.3%) approximately EGC (19.9 +/- 2.0%). Trolox (10 microM) was used as the standard for comparative purposes and was found to be less effective than the polyphenols in inhibiting tyrosine nitration (13.6 +/- 2.9%). The catechin polyphenols were also found to offer protection from peroxynitrite-induced modification of critical amino acids of apolipoprotein B-100 of LDL which contribute towards its surface charge.