Metabolic pharmacokinetics of early chronic alcohol consumption mediated by liver alcohol dehydrogenases 1 and 3 in mice.

BACKGROUND AND AIM: Alcohol dehydrogenases (ADHs) 1 and 3 are responsible for systemic alcohol metabolism. The current study investigated the contribution of liver ADH1 and ADH3 to the metabolic pharmacokinetics of chronic alcohol consumption (CAC). METHODS: The 9-week-old male mice of different ADH genotypes (wild-type [WT], Adh1-/- , and Adh3-/- ) were administered with 10% ethanol solution for 1 month, followed by acute ethanol administration (4.0 g/kg). The alcohol elimination rate (AER), area under the blood alcohol concentration curve (AUC), and the maximum blood alcohol concentration (Cmax ) were calculated. The liver content, activity, and mRNA levels of ADH were evaluated. RESULTS: Chronic alcohol consumption increased the AER and reduced the AUC in all ADH genotypes. The increased ADH1 content was correlated with AER in WT mice but not in the Adh3-/- mice. Similarly, the increased ADH3 content was also correlated with AER in both WT and Adh1-/- mice. The Cmax was significantly higher in Adh3-/- control mice than in WT control mice. It decreased in the Adh1-/- mice by CAC along with an increase in the ADH3 content. CONCLUSIONS: Alcohol dehydrogenases 1 and 3 would accomplish the pharmacokinetic adaptation to CAC in the early period. ADH1 contributes to the metabolic pharmacokinetics of CAC with a decrease in AUC in conjunction with an increase of AER by increasing the enzyme content in the presence of ADH3. ADH3 also contributes to a decrease in AUC in conjunction with not only an increase in AER but also a decrease in Cmax by increasing the enzyme content.

Biochemical and molecular responses of cyprinids in two Mediterranean lacustrine ecosystems: Opportunities for ecological assessment and biomonitoring.

Lacustrine ecosystems have been altered by accelerating pollution, excessive nutrient and organic load, water abstraction, and are susceptible to climate change. Hence, suggesting sensitive and reliable biomarkers for early assessments of their status is of urgent need. In this study, two freshwater commercial fish species, Cyprinus carpio (carp) and Carassius gibelio (prussian carp) from two lakes (i.e. Koronia and Volvi, Northern Greece) with different anthropogenic pressures were used and a battery of biochemical and molecular biomarkers related to stress response were analyzed in fish gills and liver. In parallel, water physicochemical parameters (T, DO, pH, conductivity, salinity), BOD5 and nutrient (N-NO3, N-NO2, N-NH4, P-PO4) concentrations were measured. Results showed that Lake Koronia had higher conductivity and salinity values and N-NO2 concentrations. Levels of Heat Shock Response (HSR), MAPK phosphorylation, protein carbonylation, lipid peroxidation products, Bax/Bcl-2 ratio, ubiquitination and caspases were increased in gills and liver of both fish species sampled from Lake Koronia in relation to those of Lake Volvi. Likewise, liver lipid content was increased in both fish species sampled from Lake Koronia compared to those sampled from Lake Volvi. The results indicate and reflect the higher environmental degradation that prevails in Lake Koronia ecosystem in comparison to that of Lake Volvi. The fish species studied showed different susceptibility depending on the biomarkers examined. In addition, our results from both examined species provide insight into the mechanisms involved in acclimatization to stressful environments and support the role of the studied biomarkers as sensitive and reliable tools for ecological assessments of lake ecosystems in biomonitoring studies.