© 1988 Oxford University Press
research-article |
Acute Toxicity of Helenalin in BDF1 Mice1,2
,4,*
*Curriculum in Toxicology North Carolina 27514
Division of Medicinal Chemistry North Carolina 27514
Department of Biochemistry North Carolina 27514
Department of Pathology, University of North Carolina, Chapel Hill North Carolina 27514
Received May 1, 1987; accepted October 6, 1987
Acute Tyyoxicity of Helenalin in BDF1 Mice. CHAPMAN, D. E., ROBERTS, G. B., REYNOLDS, D. J., GRIPPO, A. A., HOLBROOK, D. J., HALL, I. H., CHANEY, S. G., CHANG, J., AND LEE, K. H. (1988). Fundam. Appl. Toxicol 10, 302-312. The acute toxicity of helenalin, a sesquiter-pene lactone isolated from Helenium microcephalum, was examined in male BDF1 mice. The 14-day LD50 for a single ip dose of helenalin in male mice was 43 mg/kg. A single ip injection of 25 mg helenalin/kg increased serum alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea nitrogen (BUN), and sorbitol dehydrogenase within 6 hr of treatment. Multiple helenalin exposures, ip injection of 25 mg helenalin/kg for 3 days, increased differential poly-morphonuclear leukocyte counts and decreased lymphocyte counts. Serum ALT, BUN, and cholesterol levels were also increased by multiple helenalin exposures at 25 mg helenalin/kg/ day. Helenalin significantly reduced liver, thymus, and spleen relative weights and histologic evaluation revealed substantial effects of multiple helenalin exposures on lymphocytes of the thymus, spleen, and mesenteric lymph nodes. No helenalin-induced histologic changes were observed in the liver or kidney. Multiple helenalin exposures (25 mg/kg/day) significantly inhibited hepatic microsomal enzyme activities (aminopyrine demethylase and aniline hydroxylase) and decreased microsomal cytochromes P-450 and 65 contents. Three concurrent days of diethyl maleate (DEM) pretreatment (3.7 mmol DEM/kg, 0.5 hr before helenalin treatment) significantly increased the toxicity of helenalin exposure. The present studies indicate that the hepatic microsomal drug metabolizing system and lymphoid organs are particularly vulnerable to the effects of helenalin. In addition, helenalin toxicity is increased by DEM pretreatments which have been shown to decrease glutathione concentrations.