Inhibition of proliferation of fibroblasts by lazaroids (21-aminosteroids).
Lazaroids (21-aminosteroids) are a novel group of compounds that inhibit lipid peroxidation in biological systems and protect cells from oxidative damage during tissue injury. In vivo efficacy of lazaroids has been demonstrated in a variety of animal models of traumatic or ischemic injury of central nervous system (1-6). However, very little is known about the affects of lazaroids on cellular responses associated with tissue repair and remodeling eg cell proliferation and synthesis of extracellular matrix. In the present study, we show that lazaroids and certain related compounds inhibit cell proliferation in vitro. Light microscopic examination and determination of release of intracellular enzyme, lactate dehydrogenase suggested that cell growth inhibition by lazaroids was not due to cell death resulting from cytotoxic effects. Examination of several lazaroid related antioxidants and other known antioxidants eg vitamin E and Probucol showed that compounds with similar antioxidant potential did not exhibit identical antiproliferative activity, suggesting that cell growth inhibition by lazaroids may be unrelated to their antioxidant action. These results may have implication in the therapeutic actions of lazaroids.
Singh
J P
JP
Cardiovascular Research, Lilly Research Laboratory, Indianapolis, IN 46285.
Bonin
P D
PD
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D005021:Ethylamines / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010879:Piperazines / Q000494:pharmacology; D011281:Pregnatrienes / Q000494:pharmacology; D011341:Probucol / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D013256:Steroids / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D005021:Ethylamines; D010879:Piperazines; D011281:Pregnatrienes; D011725:Pyridines; D013256:Steroids; C069980:U 75412E; C072017:U 78518F; D014810:Vitamin E; D007770:L-Lactate Dehydrogenase; C053356:U 74500A; D011341:Probucol; C053355:tirilazad