title: Pyrroloquinoline quinone-secreting probiotic Escherichia coli Nissle 1917 ameliorates ethanol-induced oxidative damage and hyperlipidemia in rats.
abstract: BACKGROUND
  Chronic ethanol (EtOH) consumption is associated with oxidative tissue damage, decrease in antioxidant enzyme activities, and increase in hepatic and plasma lipids. This study investigates the effect of modified probiotic Escherichia coli Nissle 1917 (EcN) secreting pyrroloquinoline quinone (PQQ) against EtOH-induced metabolic disorder in rats.
  
  
  METHODS
  Male Charles Foster rats were gavaged with EtOH (5 g/kg body weight [acute study] and 3 g/kg body weight per day for 10 weeks [chronic study]).
  
  
  RESULTS
  Pretreatment of PQQ, vitamin C, and PQQ-secreting EcN prevented acute EtOH-induced oxidative damage in rats reflected by reduced lipid peroxidation in blood and liver and increased hepatic reduced glutathione. However, PQQ given externally was found to be most effective against acute EtOH toxicity. In the chronic study, rats treated with PQQ-secreting EcN showed remarkable reduction in oxidative tissue damage (liver, colon, blood, and kidney) with significant increase in antioxidant enzyme activities as compared to only EtOH-treated rats. Additionally, these rats had significantly lowered hepatic and plasma lipid levels with concomitant reduction in mRNA expression of fatty acid synthase (0.5-fold) and increase in mRNA expression of acyl coenzyme A oxidase (2.4-fold) in hepatic tissue. Antioxidant and hyperlipidemic effects of PQQ-secreting EcN are correlated with increased colonic short chain fatty acids (SCFAs; i.e., acetate, propionate, and butyrate) levels, and PQQ concentration in fecal samples (2-fold) and liver (4-fold). Extracted PQQ and vitamin C were given once a week, but they did not exhibit any ameliorative effect against chronic EtOH toxicity.
  
  
  CONCLUSIONS
  Accumulated PQQ in tissues prevents hepatic and systemic oxidative damage. PQQ along with SCFAs reduced hyperlipidemia, which can be correlated with changes in mRNA expression of hepatic lipid metabolizing genes. Our study suggests that endogenous generation of PQQ by EcN could be an effective strategy in preventing alcoholic liver disease.
authors.affiliation: Molecular Microbial Biochemistry Laboratory, Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Singh
authors.forename: Sumeet K
authors.initials: SK
authors.lastname: Pandey
authors.forename: Gattupalli
authors.initials: G
authors.lastname: Naresh Kumar
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004926:Escherichia coli / Q000378:metabolism*; D000431:Ethanol / Q000009:adverse effects*; D006949:Hyperlipidemias / Q000139:chemically induced / Q000178:diet therapy* / Q000517:prevention & control; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D045542:PQQ Cofactor / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019936:Probiotics / Q000627:therapeutic use*; D051381:Rats
chemical_list: D000975:Antioxidants; D000431:Ethanol; D045542:PQQ Cofactor; D001205:Ascorbic Acid
keywords: E. coli Nissle 1917; Ethanol; Hyperlipidemia; Oxidative Damage; Pyrroloquinoline Quinone