Evaluation of the acute and subacute toxicity of a choleretic phloracetophenone in experimental animals.
Toxicity of a choleretic compound, phloracetophenone (2,4,6-trihydroxyacetophenone; THA) was investigated in mice, rats and hamsters. Acute toxicity of THA was observed to be dependent on species and route of administration, but not sex and age. LD(50) values for an acute toxicity of a single i.p. administration to adult male hamsters and mice were 338 and 365 mg/kg BW, respectively. It was significantly increased to 489 mg/kg BW in adult male rats and greatly increased by i.g. route. Subacute toxicity was investigated in adult male mice by giving THA at a doses of 37-300 mg/kg BW/day, i.g. for 30 consecutive days. High doses of THA induced periportal hepatocyte degeneration whereas plasma concentrations of alanine and aspartate aminotransferases, bilirubin, and blood urea nitrogen, and hepatic triglyceride content were only slightly increased. The possible therapeutic effect of the choleretic THA was evaluated in the ethinylestradiol (EE)-induced cholestasis. THA enhanced the hepatic clearance of sulfobromophthalein and decreased the elevated plasma alkaline phosphatase in EE-cholestatic rats to control levels. These results suggested that THA at biologically active choleretic dose had low toxicity, it might be safe for further development as a therapeutic agent for a short period of treatment in cholestasis.
Piyachaturawat
Pawinee
P
Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajatevee, Bangkok 10400, Thailand. scppy@mahidol.ac.th
Tubtim
Chatsuda
C
Chuncharunee
Aporn
A
Komaratat
Prayad
P
Suksamrarn
Apichart
A
D000098:Acetophenones / Q000633:toxicity*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000187:drug effects; D002756:Cholagogues and Choleretics / Q000633:toxicity*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004997:Ethinyl Estradiol / Q000633:toxicity; D005260:Female; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects; D008297:Male; D008647:Mesocricetus; D051379:Mice; D051381:Rats; D017208:Rats, Wistar
D000098:Acetophenones; D002756:Cholagogues and Choleretics; D004997:Ethinyl Estradiol; C107067:2,4,6-trihydroxyacetophenone; D000251:Adenosine Triphosphatases