Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by LINDAMOOD, C.
Right arrow Articles by HILL, D. L.
Right arrow Search for Related Content
PubMed
Right arrow Articles by LINDAMOOD, C., III
Right arrow Articles by HILL, D. L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1990 Oxford University Press

other

Pharmacological and Toxicological Properties of Arotinoids SMR-2 and SMR-6 in Mice1

CHARLES LINDAMOOD, III2, FREDERICK O. COPE, DIRCK L. DILLEHAY3,*, MICHAEL P. EVERSON{dagger}, HERSCHELL D. GILES, EDDIE W. LAMON*, DENNIS J. MCCARTHY, JAMES L. SARTIN{ddagger} and DONALD L. HILL

Keltering-Meyer Laboratory, Southern Research Institute Post Office Box 55305, Birmingham, Alabama 35255-5305 *Departments of Surgery, Microbiology and Comparative Medicine, VA Medical Center and University of Alabama Birmingham, Alabama 35294 {dagger}Department of Medicine, University of Alabama Birmingham, Alabama 35294 {ddagger}Department of Physiology and Pharmacology, School of Veterinary Medicine, Aubum University Auburn, Alabama 36849

Received October 14, 1988; accepted July 3, 1989

Pharmacological and Toxicological Properties of Arotinoids SMR-2 and SMR-6 in Mice. LINDAMOOD, C, III, COPE, F. O., DILLEHAY, D. L., EVERSON, M. P., GILES, H. D., LAMON, E. W., MCCARTHY, D. J., SARTIN, J. L., AND HILL, D. L. (1990). Fundam. Appl. Toxicol. 14, 15–29. Studies were conducted to define primary pharmacological and toxicological properties of two arotinoids, SMR-2 and SMR-6, in male B6D2F1 mice. Mice were gavaged daily for up to 22 days with retinoids in corn oil (0.1, 0.2, or 0.4 mg/kg day SMR-2 or SMR-6 or 2.5, 10, or 30 mg/kg all-trans-retinoic acid as a reference control). Toxicological and biochemical end-points were assayed after 8, 15, and 22 days. At toxic doses, i.e., those inducing weight loss, morphological changes were observed in skin, lymph nodes, spleen, bone marrow, liver, thymus, forestomach, adrenal, bone, and testes. Biochemical alterations included elevated serum alkaline phosphatase, corticosterone, and interleukins–1, –2, and –3. Additional immune alterations included increased responsiveness of spleen cells to both thymus-dependent and thymus-inde-pendent mitogens and increases in the total number of B cells in the spleen. At doses not inducing weight loss, target organ effects included the appearance of plasma cells and infiltration of polymorphonuclear cells in lymph nodes; myeloid cell hypercellularity in bone marrow, hema-topoiesis in spleen; subacute inflammation in forestomach; and periportal cytoplasmic vacuo-lization in liver. At the low doses, SMR-2 resulted in decreased responsiveness of spleen cells to mitogens and SM R-6 caused increased responsiveness. SMR-6 also increased interleukin-1 and -2 production at low doses. Biochemical effects included reduced activities of liver aryl hydrocarbon hydroxylase (AHH) and soluble brain protein kinase C. Overall, the results suggest that leukcopoiesis and reduced liver AHH and reduced soluble protein kinase C activities are the primary and initial pharmacological and toxicological effects of retinoids.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.