Chronic voluntary exercise may alter hepatobiliary clearance of endogenous and exogenous chemicals in rats.
A chronic voluntary exercise paradigm, which mimics the exercise pattern of many humans, influences the hepatic clearance of several organic anions and a bile acid, whereas a neutral organic compound is seemingly unaffected. To extend these observations, the present work has evaluated in female Sprague-Dawley rats the effect of 6 weeks of voluntary running on the hepatobiliary elimination of endogenous bile acids and glutathione and exogenously injected rose bengal, digoxin, and acetaminophen. Inactive rats had mobility limited to their cages, whereas exercised rats had free access to a 44-in running wheel. In comparison to weight-matched sedentary rats, the exercised rats ran 4.3 +/- 0.3 miles/day, consumed 45% more food daily, had slightly greater liver/body weight ratios, and slightly elevated basal bile flow rates. Biliary excretion of endogenous bile acids was increased significantly, and excretion of reduced and oxidized glutathione was increased in exercised rats by 190% and 173% of sedentary levels, respectively. Total clearance, biliary clearance, and maximal biliary excretion of the injected organic anion rose bengal (60 mumol/kg) were elevated in exercised rats by 86%, 440%, and 85%, respectively. In contrast, there were no observed differences in pharmacokinetic parameters, serum elimination, or biliary excretion for the clinically important cardiac glycoside digoxin (dose of 100 nmol/kg). Finally, study of the analgesic acetaminophen (330 mumol/kg) revealed that total and biliary clearances were increased by 37% and 42%, respectively, in exercised rats, whereas steady-state volume of distribution and elimination half-life were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
Watkins
J B
JB
Medical Sciences Program, Indiana University School of Medicine, Bloomington 47405.
Crawford
S T
ST
Sanders
R A
RA
D000082:Acetaminophen / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001659:Biliary Tract / Q000378:metabolism*; D001692:Biological Transport; D004077:Digoxin / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D009043:Motor Activity / Q000502:physiology*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012395:Rose Bengal / Q000493:pharmacokinetics*; D015238:Sulfotransferases / Q000378:metabolism; D013997:Time Factors
D001647:Bile Acids and Salts; D012395:Rose Bengal; D000082:Acetaminophen; D004077:Digoxin; D015238:Sulfotransferases; D005978:Glutathione