RESUMO
Type 2 diabetes mellitus (T2DM) is characterised by chronic hyperglycaemia. Despite the efficacy of conventional pharmacotherapy, some individuals do not reach glycaemic goals and require adjuvant therapies. Taurine, a semi-essential amino acid, decreases blood glucose and cholesterol levels in rodents and humans. However, glycated hemoglobin (HbA1c) has not been evaluated in randomised controlled trials after taurine treatment for more than 12 weeks. This study aims to evaluate the effect of taurine administration on glycaemic, lipid, inflammatory, anthropometric and dietary parameters in individuals with T2DM. A randomised, double-blind, placebo-controlled clinical trial will be conducted at the Clinical Research Center of a tertiary public hospital. Participants with T2DM (n 94) will be recruited and randomised to receive 3 g of taurine or placebo, twice/day, orally, for 12 weeks. Blood samples will be collected before and after 12 weeks of treatment, when HbA1c, fasting glucose, insulin, albuminuria, creatinine, total cholesterol and fractions, triglycerides, C-reactive protein, TNF-α, IL 1, 4, 5, 6, 10 and 13 will be evaluated. Anthropometric parameters and 24-hour food recall will also be evaluated. The study will evaluate the effect of taurine treatment on biochemical and anthropometric parameters in individuals with T2DM. These results will guide the decision-making to indicate taurine treatment as an adjunct in individuals with T2DM who have not reached their glycaemic goal.
Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Glicemia/metabolismo , Método Duplo-Cego , Lipídeos , Colesterol , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Interactions on neurotransmitter systems in the reward pathways may explain the high frequency of combined use of alcohol and cigarettes in humans. In this study, we evaluated some behavioral and neurochemical changes promoted by chronic exposure to alcohol and cigarette smoke in rats. Adult rats were administered with 2 g/kg alcohol (v.o.) or/and inhaled the smoke from 6 cigarettes, twice/day, for 30 days. Behavioral tests were performed 3 h after the alcohol administration and 1 h after the last exposure to cigarette smoke in the morning. Cerebrospinal fluid was collected for glutamate determination and the hippocampus was dissected for GABAA and NMDA receptor subunits mRNA expression determination. Results showed that the combined use of alcohol and cigarette smoke (ALTB) in rats increased the locomotor activity and all interventions decreased anxiety-like behaviors. Despite being on a short-term withdrawal, the cigarette smoke exposure decreased the percentage of open arm entries in the elevated plus maze test, which was prevented by combined use with alcohol. Even though GABAA and glutamate receptor subunits expression did not change in the hippocampus, glutamate levels were significantly higher in the cerebrospinal fluid from ALTB rats. Therefore, we showed that the combined use of alcohol and cigarette maintained a psychostimulant effect after a short-term withdrawal that was associated with the elevated glutamatergic activity. The combined use also prevented anxiety-like signs in cigarette smoke exposure rats, decreasing an adverse effect caused by nicotine withdrawal. These results could explain, in part, the elevated frequency of combined use of these two drugs of abuse in humans.
Assuntos
Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Depressores do Sistema Nervoso Central/farmacologia , Fumar Cigarros , Etanol/farmacologia , Ácido Glutâmico/líquido cefalorraquidiano , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Locomoção/efeitos dos fármacos , Receptores de GABA-A/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Depressores do Sistema Nervoso Central/administração & dosagem , Quimioterapia Combinada , Etanol/administração & dosagem , Ácido Glutâmico/efeitos dos fármacos , Aprendizagem em Labirinto , RNA Mensageiro , Ratos , Ratos Wistar , Receptores de GABA-A/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacosRESUMO
BACKGROUND AND OBJECTIVES: Smokers currently have no defined restrictions for blood donation. However, cigarette smoke contains toxic substances such as carbon monoxide (CO) and trace elements that can affect the packed red blood cells (PRBCs) quality and safety of transfusion. This study evaluated the effects of smoking on the concentration of essential and trace elements and on carboxyhemoglobin (COHb) levels in PRBCs from smoker donors. MATERIALS AND METHODS: A matched case-control study was conducted to compare COHb levels, determined by the CO-oximetry method, and levels of trace (Cd, Pb, Cr, Ni, As and Hg) and essential (Ca, Mg, Cu, Fe, Mn, Mo, Se and Zn) elements evaluated by inductively coupled plasma mass spectrometry, in PRBCs from smoker (n = 36) and non-smoker (n = 36) donors at Hospital de Clínicas de Porto Alegre, Brazil. RESULTS: Mean COHb level was 14 times higher in the PRBCs obtained from smoker donors (5·9 [4·0-9·1] vs. 0·4 [0·2-0·8]%). Cadmium (1·0 [1·0-1·8] µg/l vs. undetectable) and lead (27 [21-36] vs. 19 [14-26] µg/l) levels were significantly higher in the PRBCs from smokers. Moreover, except for molybdenum, levels of all essential elements were lower in smoker PRBCs. CONCLUSION: The PRBCs donated by smokers contain toxic elements that are probably not safe for transfusion in children. Our results might support changes in the current guidelines of blood banks to improve the transfusion safety through inclusion of inquiry about smoking in the clinical screening, labelling and reserve PRBCs from smoker donors for adults or less critical recipients.
Assuntos
Doadores de Sangue/estatística & dados numéricos , Fumantes/estatística & dados numéricos , Fumar/sangue , Oligoelementos/sangue , Reação Transfusional/epidemiologia , Adulto , Bancos de Sangue/normas , Estudos de Casos e Controles , Eritrócitos/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/epidemiologiaRESUMO
Devastating effects of exposure to alcohol and tobacco smoke on health are extensively reported in the literature. However, few studies have attempted to elucidate the consequences of their combined use on the central nervous system. Here we studied the effect of this combined use on some oxidative, inflammatory, and neurotrophic parameters in the hippocampus, striatum, and frontal cortex of rats. Adult Wistar rats were allocated into control (CT), alcohol (AL), tobacco smoke (TB), or combined (ALTB) groups. Rats were exposed to environmental air (CT and AL groups) or to the smoke from six cigarettes (TB and ALTB groups) immediately after tap water (CT and TB) or 2 g of alcohol/kg (AL and ALTB) oral gavage administration, twice a day, for 4 weeks. On day 28, rats were euthanized and areas of the brain were dissected to evaluate some cellular redox parameters, pro-inflammatory cytokine levels, and brain-derived neurotrophic factor (BDNF) levels. A one-way analysis of variance showed that the ALTB combined treatment significantly increased oxidative stress levels in the hippocampus. ALTB also increased interleukin-1ß levels in the striatum and frontal cortex and tumoral necrosis factor-α levels in the frontal cortex compared with those of AL, TB, and CT rats. Combined treatment also decreased the BDNF levels in the frontal cortex of rats. Oxidative damage was found, more importantly, in the hippocampus, and inflammatory parameters were extended to all areas of the brain that were studied. Our results showed an interaction between alcohol and tobacco smoke according to the area of the brain, suggesting an additional risk of neural damage in alcoholics who smoke.
Assuntos
Depressores do Sistema Nervoso Central/efeitos adversos , Corpo Estriado/efeitos dos fármacos , Etanol/efeitos adversos , Lobo Frontal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corpo Estriado/metabolismo , Lobo Frontal/metabolismo , Glutamato-Amônia Ligase/metabolismo , Hipocampo/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos WistarRESUMO
Diabetes is a chronic metabolic disease associated with oxidative stress, damage to biomolecules such as DNA, and neuroinflammation. Taurine, a sulfur-containing amino acid widespread in the brain, has neuroprotective properties that might prevent tissue injury and DNA damage induced by chronic hyperglycemia. We evaluated the effects of chronic taurine treatment on oxidative stress parameters, DNA damage and inflammatory markers in the frontal cortex, and hippocampus of streptozotocin-induced diabetic rats. Diabetic rats displayed increased levels of reactive oxygen species (ROS) and DNA damage in both areas, evidencing the pro-oxidant effects of diabetes in the brain. Moreover, this condition increased levels of several inflammatory mediators, such as IL-6, IL-12, TNF-γ, and IFN-α, more pronouncedly in the hippocampus. Supporting our hypothesis, taurine treatment reduced ROS, DNA damage, and inflammatory cytokine levels, providing evidence of its beneficial effects against genotoxicity and neuroinflammation associated with diabetes. Our data endorse the necessary clinical trials to evaluate the efficacy and safety of taurine supplementation in the prevention and treatment of neurochemical and metabolic alterations related to diabetes.
Assuntos
Encéfalo/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Taurina/farmacologia , Animais , Antioxidantes/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Citocinas/análise , Dano ao DNA/efeitos dos fármacos , Diabetes Mellitus Experimental/patologia , Masculino , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Taurina/uso terapêuticoRESUMO
Alcoholism has been characterized as a systemic pro-inflammatory condition and alcohol withdrawal has been linked to various changes in the brain homeostasis, including oxidative stress and glutamate hyperactivity. N-acetylcysteine (NAC) is an anti-inflammatory and antioxidant multi-target drug with promising results in psychiatry, including drug addiction. We assessed the effects of NAC on the serum and brain inflammatory cytokines after cessation of chronic alcohol treatment in rats. Male Wistar rats received 2 g/kg alcohol or vehicle twice a day by oral gavage for 30 days. Rats were treated, from day 31 to 34, with NAC (60 or 90 mg/kg) or saline, intraperitoneally, once daily. Rats were sacrificed at day 35, trunk blood was collected and the frontal cortex and hippocampus dissected for assessment of TNF-α, IL-1ß, IL-6, IL-18, IL-10. NAC prevented the increase of pro-inflammatory cytokines and the decrease of anti-inflammatory cytokine in the frontal cortex and hippocampus. No changes were observed on serum cytokines. We conclude that NAC protects against inflammation induced by chronic (30 days) alcohol ingestion followed by 5 days cessation in two rat brain areas. Because inflammation has been documented and associated with craving and relapse in alcoholics, the data revealed by this study points to the validity of NAC clinical evaluation in the context of alcohol detoxification and withdrawal.
Assuntos
Acetilcisteína/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Encéfalo/metabolismo , Etanol/toxicidade , Mediadores da Inflamação/metabolismo , Acetilcisteína/farmacologia , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Consumo de Bebidas Alcoólicas/imunologia , Consumo de Bebidas Alcoólicas/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Encéfalo/efeitos dos fármacos , Etanol/administração & dosagem , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/metabolismo , Mediadores da Inflamação/antagonistas & inibidores , Masculino , Ratos , Ratos WistarRESUMO
Clinical and preclinical studies have shown that diabetic individuals present more depressive behaviors than non-diabetic individuals. Taurine, one of the most abundant free amino acids in the central nervous system, modulates a variety of biological functions and acts as an agonist at GABAA receptors. Our objective was to assess the antidepressant effect of taurine in diabetic rats. Additionally, we studied the effect of taurine on weight gain, water and food intake, and blood glucose levels in diabetic and non-diabetic rats. Male Wistar rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were administered daily 0, 25, 50 or 100 mg/kg of taurine (n = 10 per subgroup) intraperitoneally. After 28 days of treatment, the animals were exposed to the forced swimming test, and their behaviors were recorded. Weight gain, water and food intake, and blood glucose levels were measured weekly. Our results showed that STZ rats had a higher immobility duration than CTR rats, and taurine decreased this depressive-like behavior in STZ rats at doses of 25 and 100 mg/kg. Both of these doses of taurine also decreased water intake and improved weight gain in STZ rats. All doses of taurine decreased the water intake in CTR rats. Taurine, at a dose of 100 mg/kg, decreased food intake and blood glucose levels in STZ rats. Because taurine is a GABA agonist and both amino acids are lower in the plasma of diabetic and depressive individuals, we hypothesize that taurine may represent a new adjuvant drug for the treatment of depression in diabetic individuals.