title: Age-associated decline of hepatic handling of cholephilic anions in humans is reverted by S-adenosylmethionine (SAMe).
abstract: Decreased fluidity of hepatocyte plasma membrane may contribute to the age-associated changes of liver function. This study aimed at investigating whether the hepatic clearance of organic anions declines with age and whether S-adenosylmethionine (SAMe), a substance proven to be effective in reversing the age-related decrease of membrane fluidity, might influence this process. Nicotinic acid (NA) half-life and serum bilirubin pharmacokinetics after NA load (5.9 mumol/kg body weight i.v.) were studied in 10 healthy young males (YM) aged 14-28 years and in 10 healthy elderly males (EM) aged 65-81 years, before and after SAMe administration (800 mg/day intravenously for 10 days). At baseline, EM showed serum total bilirubin (STB) levels significantly higher than YM. Similarly, the bilirubinaemic mean curves, STB peak and STB time curve concentration after NA load, expressed as area under the curve (AUC), were significantly higher in EM than in YM (p less than 0.01). NA half-life was also significantly prolonged in the aged group (p less than 0.001). SAMe treatment was followed by a significant decrease of basal STB, STB peak and AUC of STB after NA load in EM (p less than 0.01 vs pre-treatment values) while NA half-life was significantly shortened in both groups (p less than 0.001). As NA and bilirubin share a common carrier protein for hepatic uptake, bilitranslocase, the changes observed in EM may be attributed to the reduced lateral mobility of hepatocyte plasma membrane proteins occurring with age. SAMe, by improving membrane fluidity, may increase the diffusion coefficient of bilitranslocase restoring the hepatic handling of organic anions.
authors.affiliation: Istituto di Medicina Generale e Metodologia Clinica, I Facoltà di Medicina, Il Policlinico, Napoli, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Gentile
authors.forename: M
authors.initials: M
authors.lastname: Persico
authors.forename: C
authors.initials: C
authors.lastname: Orlando
authors.forename: C
authors.initials: C
authors.lastname: Le Grazie
authors.forename: C
authors.initials: C
authors.lastname: Di Padova
authors.forename: M
authors.initials: M
authors.lastname: Coltorti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000838:Anions / Q000378:metabolism; D001663:Bilirubin / Q000097:blood; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology; D009525:Niacin / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000494:pharmacology*
chemical_list: D000838:Anions; D009525:Niacin; D012436:S-Adenosylmethionine; D001663:Bilirubin