Potentiation of acetaminophen hepatotoxicity by acute physical exercise in rats.
Effects of acute physical exercise on the acetaminophen-induced hepatotoxicity were examined in adult female rats. Rats were forced to move at a speed of 10 m/min for 2 hr in a rotating cage. Immediately following the exercise bout rats were treated with acetaminophen (APAP; 700 mg/kg, i.p.). The physical exercise enhanced the hepatotoxicity of APAP as shown by increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities measured 24 hr following the treatment. A significant decrease in hepatic glutathione (GSH) was observed in the rats forced to exercise suggesting that the enhancement of APAP hepatotoxicity was associated with the depression of this endogenous tripeptide. The role of adrenergic stimulation in the exercise-induced hepatic GSH depression was examined by pretreating the animals with a receptor specific adrenergic antagonist, such as prazosin HCl (15 mg/kg, i.p.), propranolol HCl (15 mg/kg, i.p.), and yohimbine HCl (15 mg/kg, i.p.) 15 min prior to the exercise bout, but neither of the antagonists prevented the GSH depression. Administration of alpha-tocopherol acetate (450 mg/kg/day for 3 days and 150 mg/kg on day 4, i.p.) did not affect the exercise-induced GSH depression or lipid peroxidation in liver homogenates as determined by increases in malondialdehyde formation. These results suggest that neither adrenergic stimulation nor oxidative stress plays a significant role in the enhancement of APAP hepatotoxicity and hepatic GSH depression induced by acute physical exercise.
Yoon
M Y
MY
College of Pharmacy, Seoul National University, Korea.
Kim
S N
SN
Kim
Y C
YC
D000082:Acetaminophen / Q000494:pharmacology* / Q000633:toxicity; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000410:Alanine Transaminase / Q000097:blood; D000700:Analgesics / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000700:Analgesics; D014810:Vitamin E; D015016:Yohimbine; D000082:Acetaminophen; D008315:Malondialdehyde; D011433:Propranolol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D011224:Prazosin