Chlamydial and periodontal pathogens induce hepatic inflammation and fatty acid imbalance in apolipoprotein E-deficient mice.

Periodontitis and Chlamydia pneumoniae infection are independent risk factors for cardiovascular diseases. The aim of this study was to investigate the effect of C. pneumoniae and Aggregatibacter actinomycetemcomitans infection on hepatic inflammation and lipid homeostasis of apolipoprotein E-deficient mice. Mice were infected with viable C. pneumoniae intranasally three times for chronic infection or once for acute infection. Viable A. actinomycetemcomitans was administered 10 times intravenously alone or in concert with C. pneumoniae. Hepatic alterations were assessed by histochemistry, lipid quantification, and fatty acid profile analysis. The RNA expression levels and the presence of pathogens in the livers and lungs were detected by quantitative real-time PCR. Both pathogens were detected in the livers of the infected animals. Chronic C. pneumoniae infection induced marked changes in hepatic lipid homeostasis. A. actinomycetemcomitans infection resulted in inflammatory cell infiltration into the liver, accompanied by elevated hepatic RNA expression levels of inflammation-related genes and higher serum amyloid A and lipopolysaccharide concentrations. Our results indicate that proatherogenic pathogens infect the liver, causing proinflammatory alterations and lipid disturbances. This infection may maintain chronic systemic inflammation attributable to atherogenesis.

Acceleration of ethanol and acetaldehyde oxidation by D-glycerate in rats.

The aim of the present study was to investigate whether d-glycerate (glycerate) could accelerate ethanol and acetaldehyde (AcH) oxidation in vivo in rats by circumventing the rate-limiting step, that is, the reoxidation of the reduced form of nicotinamide adenine dinucleotide. Male rats belonging to the ANA (Alko, nonalcohol) and AA (Alko, alcohol) rat lines were challenged with 1.2 g ethanol per kilogram with or without glycerate administration (0.1-1.0 g/kg). Blood ethanol, blood AcH, and liver free glycerol concentrations were determined during ethanol intoxication. Glycerate treatment, regardless of the dose, accelerated ethanol elimination by approximately 25% (P < .001) in the ANA animals. Glycerate also accelerated the AcH oxidation, but perhaps not as much as the ethanol oxidation, as indicated by a trend toward elevated AcH levels. In the experiments with the AA rats, glycerate treatment elevated hepatic free glycerol levels by about 50% (P < .05) during alcohol intoxication. The acceleration of ethanol and AcH oxidation in conjunction with elevated glycerol levels by the treatment with glycerate supports the hypothesis that the aldehyde dehydrogenase-mediated AcH oxidation can be coupled with the reduction of glycerate to d-glyceraldehyde catalyzed by the same enzyme. Such a coupling should increase the availability of the oxidized form of nicotinamide adenine dinucleotide and thus accelerate both ethanol and AcH oxidation. Further studies are needed to investigate how the AcH could be even more efficiently oxidized to reduce the harmful effects of ethanol-derived AcH.

Protective function of complement against alcohol-induced rat liver damage.

The complement system can promote tissue damage or play a homeostatic role in the clearance and disposal of damaged tissue. We assessed the role of the terminal complement pathway in alcohol-induced liver damage in complement C6 (C6-/-) genetically deficient rats. C6-/- and corresponding C6+/+ rats were continuously exposed to ethanol by feeding ethanol-supplemented liquid diet for six weeks. Liver samples were analyzed for histopathology and complement component deposition by immunofluorescence microscopy. Prostaglandin E receptors and cytokine mRNA levels were analyzed by RT-PCR and plasma cytokines by ELISA. Deposition of complement components C1, C3, C8 and C9 was observed in C6+/+ rats, but not in C6-/- animals. The histopathological changes, the liver weight increase and the elevation of the plasma pro-/anti-inflammatory TNF-alpha/IL-10 ratio were, on the other hand, more marked in C6-/- rats. Furthermore, ethanol enhanced the hepatic mRNA expression of the prostaglandin E receptors EP2R and EP4R exclusively in the C6-/- rats. Our results indicate that a deficient terminal complement pathway predisposes to tissue injury and promotes a pro-inflammatory cytokine response. This suggests that an intact complement system has a protective function in the development of alcoholic liver damage.