title: Impairment of bile secretion induced by exhaustive exercise in the rat. Protective effects of S-adenosyl-L-methionine.
abstract: The effects of strenuous exercise on the mechanisms of bile formation were studied in rats. Animals (n = 8) were exercised to exhaustion in a rodent treadmill at a speed of 24 m/min and a 12% slope. Hepatic glutathione concentration was significantly reduced (-40%) and liver malondialdehyde content significantly increased (+37%) when compared to sedentary controls (n = 6). Both serum alkaline phosphatase level and bile acid concentration were significantly higher in runners (+81% and +85%). Bile flow and the biliary secretion of bile acids were significantly reduced both in basal conditions and following an i.v. taurocholate infusion (0.5 mumol/min/100 g body wt). Biliary glutathione secretion was also significantly decreased following exercise. Cholestasis was caused by an impairment of both bile acid-dependent (BADF) and bile acid-independent fraction (BAIF) of bile flow (-25% and -29% respectively). Exercise caused a delay in the peak appearance time and a reduced biliary secretion of horseradish peroxidase, suggesting alterations in the functional integrity of the cytoskeleton. To test the protective effects of S-adenosyl-L-methionine (SAMe), rats received the drug for ten days at a daily dose of 8 mg/kg i.p. SAMe administration prevented hepatic glutathione depletion due to exercise, normalizing both bile flow and bile acid as well as glutathione secretion. Our results suggest that both glutathione depletion and alterations in fluidity and composition of hepatocyte membranes could contribute to the development of exercise-induced cholestasis.
authors.affiliation: Institute of Physical Education, University of León, Spain.
authors.forename: J G
authors.initials: JG
authors.lastname: Villa
authors.forename: M M
authors.initials: MM
authors.lastname: Almar
authors.forename: P S
authors.initials: PS
authors.lastname: Collado
authors.forename: E
authors.initials: E
authors.lastname: Llamazares
authors.forename: J
authors.initials: J
authors.lastname: González-Gallego
mesh_terms: D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002779:Cholestasis / Q000209:etiology / Q000378:metabolism; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D010805:Physical Conditioning, Animal / Q000009:adverse effects; D005082:Physical Exertion / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012436:S-Adenosylmethionine / Q000494:pharmacology*
chemical_list: D001647:Bile Acids and Salts; D012436:S-Adenosylmethionine; D005978:Glutathione