The choleretic effect of nonsteroidal anti-inflammatory drugs in total parenteral nutrition-associated cholestasis.
Cholestasis is a frequent problem in patients on total parenteral nutrition (TPN) therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs), especially aspirin, cause choleresis in animals. We studied the effect of aspirin on bile flow and bile salt secretion in TPN-associated cholestasis in rats. Four groups of 6-10 animals each received either 154 mM NaCl (saline) or 2.5% amino acid solution (TRAVASOL, Travenol, Israel) and 10% glucose i.v. (TPN) for 3 h. During the second and third hours, taurocholate, the main bile salt in rats, was infused at a rate of 10 micromol/min per kg to prevent bile salt pool depletion. Aspirin, one of the main NSAIDs, was infused during the last 2 h into animals with or without TPN treatment at a rate of 100 mg/kg. Bile was directly collected from the common bile duct for 3 h. Rats given TPN showed a significant reduction in bile flow and bile salt secretion rate compared to control groups: 20.89 vs. 29.60 microl/min per kg (P <0.02) and 0.37 vs. 0.65 micromol/min per kg (P <0.0001), respectively. Aspirin had a significant choleretic effect and was able to overcome the bile flow and bile salt secretion rate reduction caused by TPN; 33.07 vs. 20.89 microl/min per kg (P <0.002) and 0.66 vs. 0.37 micromol/min per kg (P <0.0001), respectively. These results may have clinical implications for TPN-associated cholestasis.
Nussinovitch
M
M
Division of Pediatric Gastroenterology and Nutrition, Schneider Children's Medical Center of Israel, Petah Tikva.
Zahavi
I
I
Marcus
H
H
Hackelman
B
B
Dinari
G
G
D000596:Amino Acids / Q000009:adverse effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002779:Cholestasis / Q000188:drug therapy* / Q000209:etiology*; D004353:Drug Evaluation, Preclinical; D004573:Electrolytes; D005947:Glucose; D005950:Glucose Solution, Hypertonic / Q000009:adverse effects*; D008297:Male; D057947:Parenteral Nutrition Solutions; D051381:Rats; D017208:Rats, Wistar; D012996:Solutions
D000596:Amino Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001647:Bile Acids and Salts; D004573:Electrolytes; D005950:Glucose Solution, Hypertonic; D057947:Parenteral Nutrition Solutions; D012996:Solutions; C545824:amino-acid, glucose, and electrolyte solution; D005947:Glucose; D001241:Aspirin