Carbonyl compounds in different stages of vinification and exposure risk assessment through Merlot wine consumption.

The objective of this research was to estimate for the first time the transformations that the free form of some target carbonyl compounds may undergo during winemaking and assess the exposure risk to these compounds through the consumption of the Merlot commercial wines under study. Acrolein and furfural were found in grapes and the respective wines, although levels were observed to decline throughout the winemaking process. Formaldehyde was found in all stages of wine production in levels lower than the limit of quantification of the method and ethyl carbamate was not found in samples. Acetaldehyde seems to be a precursor of acetoin and 2,3-butanediol, since the levels of this aldehyde decreased along winemaking and the formation of the ester and alcohol was verified. Furfural levels decreased, while the occurrence of furan-containing compounds increased during winemaking. The formation of acetaldehyde during alcoholic fermentation and the potential environmental contamination of grapes with acrolein and furfural are considered as the critical points related to the presence of toxic carbonyl compounds in the wine. Acrolein was found in the samples under study in sufficient quantities to present risk to human health, while other potentially toxic carbonyl compounds did not result in risk. This study indicated for the first time the presence of acrolein in grapes suggesting that environmental pollution can play an important role in the levels of this aldehyde detected in wines. Reduction of the emission of this aldehyde to the environment may be achieved by replacing wood burning by another heat source in fireplaces or wood stones, and abandoning the practice of burning garbage and vegetation.

DNA Adduct Formation in the Lungs and Brain of Rats Exposed to Low Concentrations of [13C2]-Acetaldehyde.

Air pollution is a major environmental risk for human health. Acetaldehyde is present in tobacco smoke and vehicle exhaust. In this study, we show that [13C2]-acetaldehyde induces DNA modification with the formation of isotopically labeled 1, N2-propano-2'-deoxyguanosine adducts in the brain and lungs of rats exposed to concentrations of acetaldehyde found in the atmosphere of megacities. The adduct, with the addition of two molecules of isotopically labeled acetaldehyde [13C4]-1, N2-propano-dGuo, was detected in the lung and brain tissues of exposed rats by micro-HPLC/MS/MS. Structural confirmation of the products was unequivocally performed by nano-LC/ESI+-HRMS3 analyses. DNA modifications induced by acetaldehyde have been regarded as a key factor in the mechanism of mutagenesis and may be involved in the cancer risks associated with air pollution.

The "first hit" toward alcohol reinforcement: role of ethanol metabolites.

This review analyzes literature that describes the behavioral effects of 2 metabolites of ethanol (EtOH): acetaldehyde and salsolinol (a condensation product of acetaldehyde and dopamine) generated in the brain. These metabolites are self-administered into specific brain areas by animals, showing strong reinforcing effects. A wealth of evidence shows that EtOH, a drug consumed to attain millimolar concentrations, generates brain metabolites that are reinforcing at micromolar and nanomolar concentrations. Salsolinol administration leads to marked increases in voluntary EtOH intake, an effect inhibited by mu-opioid receptor blockers. In animals that have ingested EtOH chronically, the maintenance of alcohol intake is no longer influenced by EtOH metabolites, as intake is taken over by other brain systems. However, after EtOH withdrawal brain acetaldehyde has a major role in promoting binge-like drinking in the condition known as the "alcohol deprivation effect"; a condition seen in animals that have ingested alcohol chronically, are deprived of EtOH for extended periods, and are allowed EtOH re-access. The review also analyzes the behavioral effects of acetate, a metabolite that enters the brain and is responsible for motor incoordination at low doses of EtOH. Also discussed are the paradoxical effects of systemic acetaldehyde. Overall, evidence strongly suggests that brain-generated EtOH metabolites play a major role in the early ("first-hit") development of alcohol reinforcement and in the generation of relapse-like drinking.

The role of acetaldehyde in ethanol reinforcement assessed by Pavlovian conditioning in newborn rats.

RATIONALE: Animal studies indicate that central acetaldehyde, dependent on catalase metabolism of ethanol (EtOH), modulates ethanol reinforcement. Brain catalase activity and acetaldehyde (ACD) production are significantly higher in rat pups compare d with adults. Interestingly, infant rats show high EtOH affinity for alcohol consumption and are particularly sensitive to the drug's reinforcing effects. OBJECTIVES: We tested whether central ACD is necessary and sufficient to induce appetitive conditioning in newborn rats through the artificial nipple technique. METHODS: Vehicle, EtOH (100 mg%), and acetaldehyde (0.35 µmol) were administered into the cisterna magna (1 µl). Half of the animals also received a central administration of 75 µg (experiment 1) or 40 µg of D-penicillamine (experiment 2). Afterwards, pups were exposed to an olfactory cue (conditioned stimulus). One hour later, neonates were tested with an artificial nipple in the presence of the conditioned cue. Nipple attachment duration, mean grasp duration, and number of nipple disengagements served as dependent variables. RESULTS: Positive responses to the scented nipple occurred in neonates conditioned with EtOH or ACD (experiments 1 and 2). In experiment 1, there were indications that D-penicillamine weakened the reinforcing effects of EtOH and ACD. In experiment 2, D-penicillamine (40 µg) significantly inhibited appetitive conditioned responses dependent upon EtOH or ACD. CONCLUSIONS: Appetitive conditioning was observed when employing either central EtOH or ACD as unconditioned stimuli. Central abduction of ACD inhibited conditioned appetitive responsiveness to the surrogate nipple. Central ACD is involved in the determination or modulation of EtOH's motivational properties during early stages in development.

Glycolaldehyde induces oxidative stress in the heart: a clue to diabetic cardiomyopathy?

Cardiovascular complications account for 80% of the mortality related to diabetes mellitus. Hyperglycemia is believed to be the major culprit of angiopathy and cardiomyopathy. High glucose levels and oxidative stress cause elevation of Advanced Glycation End-products that are known to contribute to diabetic complications and correlate with many diseases. However, there are few reports describing the effects of glycating agents other than glucose. Here, we aimed to evaluate the effects of glycolaldehyde (GA) on oxidative stress parameters in the heart of Wistar rats. Male Wistar rats received a single injection of GA (10, 50 or 100 mg/Kg) and were sacrificed 6, 12 or 24 h after injection. As indexes of oxidative stress, we quantified protein carbonylation, lipid peroxidation and total reduced thiols. The activities of superoxide dismutase, catalase and glyoxalase I were assayed. Also, the content of N (ɛ)-(carboxymethyl)lysine (CML) was quantified. Glycolaldehyde induced an imbalance in the redox status, with increased protein carbonylation and lipoperoxidation. Catalase and glyoxalase I had a decrease in their activities. Despite the oxidative stress, we observed no increase in CML content. These results suggest that short-chain aldehydes such as GA might have a significant role in the development of diabetic cardiomyopathy.

Circulating glycolaldehyde induces oxidative damage in the kidney of rats.

Renal failure is a key pathological issue in diabetic patients. Increased levels of advanced glycation end-products (AGEs) have been associated to diabetic complications, including diabetic nephropathy. Models of AGE-treated animals have been applied to evaluate the effect of such molecules on oxidative parameters involved in the pathogenesis and evolution of diabetes disease. However, little is known about the effect of glycating agents other than glucose. Here we investigate the effect of intravenously administrated glycolaldehyde (GA) on oxidative stress parameters of the kidney. Male Wistar rats received a single injection of GA in different doses (10, 50 or 100mg/kg) and were sacrificed after 6, 12 or 24h. Activities of antioxidant enzymes catalase, superoxide dismutase and glyoxalase I were assayed. Damage to proteins and lipids were also assayed. The content of N(epsilon)-(carboxymethyl)lysine (CML) was quantified. Glycolaldehyde induced a decrease in the activity of all enzymes studied. Lipoperoxidation and protein carbonylation raised, accompanied by a decrease in sulfhydryl groups. Despite the oxidative stress generated by GA, no change was found in the content of CML, suggesting that accumulation of AGEs in the kidney might occur at later steps in the development of diabetic nephropathy.

Aversion to acetaldehyde: differences in low-alcohol-drinking (UChA) and high-alcohol-drinking (UChB) rats.

We have previously found the existence of a relation between activity of the brain mitochondrial aldehyde dehydrogenase (ALDH2) and consumption of ethanol in rats of the low-alcohol-drinking (UChA) and the high-alcohol-drinking (UChB) strains. The aim of the present study was to determine whether UChA and UChB rats also differed in sensitivity to the aversive effects of acetaldehyde (AcH). Aversion to AcH was studied by using a conditioned taste aversion (CTA) paradigm. Ethanol naive UChA and UChB rats were administered AcH intraperitoneally (50, 100, or 150 mg/kg) or saline and exposed to a banana-flavored solution during five conditioning trials. A strong dose-dependent CTA to AcH was found in UChA rats, whereas UChB rats did not show a CTA to any dose of AcH. At equal doses of AcH, cerebral venous blood AcH levels in UChA rats were consistently higher than in UChB rats, a finding that may reflect the previously observed differences in the activity of ALDH2 between these strains. However, this observation is unlikely to explain fully the differences observed because aversion to AcH was developed in the UChA strain at blood levels of AcH that did not produce any aversion in the UChB strain. These results support the suggestion that, for the first time, differences in central or systemic effects of AcH per se may play a major role in determining the aversion to AcH in drinker and nondrinker animals.

Participación de receptores J pulmonares en reflejo cardiorespiratorio provocado por acetaldehido en ratas / Pulmonary J receptors in the cardiorespiratory response induced by acetaldehyde in rats

Anteriormente demostramos que la administración endovenosa de acetaldehido (AcH) y etanol, provoca en la rata una triple respuesta refleja caracterizada por bradicardia, hipotensión y apnea, cuya vía eferente es vagal. La activación central del vago, como un mecanismo de iniciación de esta respuesta refleja se descartó mediante la inyección intracarotídea (hacia el SNC) de (AcH), la que produce hipertensión sin bradicardia. La administración de AcH en el ventrículo izquierdo no produce reflejo, y sin embargo su administración en ventrículo derecho produce una respuesta refleja mayor y con una latencia significativamente menor que por vía endovenosa. Esto sugiere la estimulación de receptores sensitivos ubicados en la circulación pulmonar. De éstos, sólo la estimulación de los receptores J pulmonares puede producir una respuesta refleja con bradicardia, hipotensión y apnea, y dada su ubicación entre el alvéolo y capilar pulmonar, son accesibles por la circulación pulmonar y por vía respiratoria. Con el objeto de precisar la participación de estos receptores en la respuesta refleja se administró AcH mediante nebulización a ratas anestesiadas y traqueotomizadas. El AcH administrado por vía respiratoria produjo la misma respuesta refleja, caracterizada por bradicardia (-52.8ñ21.73%). hipotensión (-36,9ñ12.10%) y apnea (4/7), pero con una latencia significativamente menor (p=0.0001) que por la vía endovenosa. La frecuencia respiratoria, volumen corriente y ventilación minuto no se modificaron significativamente. La vagotomía cervical bilateral bloqueó totalmente la bradicardia y la apnea, observándose una hipotensión de menor magnitud (p=0.0001) y con una latencia mayor (p=0.0001). La nebulización de solución Ringer Locke, a 10§C y a 37§C, produjo solamente hipotensión que no se modificó con vagotomía. Los resultados sugieren que la respuesta inducida por AcH, es mediada por un aumento reflejo en el tonovagal y que los neurorreceptores involucrados en la iniciación de este reflejo se ubican a nivel pulmonar y corresponderían a los receptores J pulmonares