RESUMO
Pyrroloquinoline quinone (PQQ), an aromatic tricyclic o-quinone, was identified initially as a redox cofactor for bacterial dehydrogenases. Although PQQ is not biosynthesized in mammals, trace amounts of PQQ have been found in human and rat tissues because of its wide distribution in dietary sources. Importantly, nutritional studies in rodents have revealed that PQQ deficiency exhibits diverse systemic responses, including growth impairment, immune dysfunction, and abnormal reproductive performance. Although PQQ is not currently classified as a vitamin, PQQ has been implicated as an important nutrient in mammals. In recent years, PQQ has been receiving much attention owing to its physiological importance and pharmacological effects. In this article, we review the potential health benefits of PQQ with a focus on its growth-promoting activity, anti-diabetic effect, anti-oxidative action, and neuroprotective function. Additionally, we provide an update of its basic pharmacokinetics and safety information in oral ingestion.
Assuntos
Antioxidantes/farmacologia , Suplementos Nutricionais , Hipoglicemiantes/farmacologia , Memória/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Cofator PQQ/farmacologia , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacocinética , Regulação da Expressão Gênica , Glucose/metabolismo , Humanos , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacocinética , Insulina/genética , Insulina/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/fisiologia , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacocinética , Oxirredução , Cofator PQQ/metabolismo , Cofator PQQ/farmacocinética , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Ratos , Receptor de Insulina/genética , Receptor de Insulina/metabolismoRESUMO
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.