Additive inhibition of in vitro rabbit reticulocyte heme and protein synthesis with combinations of isoniazid, chloramphenicol and ethanol.
Isoniazid, chloramphenicol and ethanol are well known hematopoietic toxins. These agents inhibit in vitro rabbit reticulocyte heme synthesis and, as a result, inhibit protein synthesis. When combinations of isoniazid (2 x 10(-3)M) and ethanol (0.1M), isoniazid and chloramphenicol (10(-3)M) or ethanol and chloramphenicol were present in the same incubation, their inhibitory effects on heme and protein synthesis were additive. These results suggest that the development of clinical hematological toxicity in man may result from additive interaction of chemically unrelated compounds which inhibit the heme synthetic pathway.
D000818:Animals; D002701:Chloramphenicol / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005914:Globins / Q000096:biosynthesis*; D006418:Heme / Q000031:analogs & derivatives* / Q000096:biosynthesis*; D006427:Hemin / Q000096:biosynthesis*; D007538:Isoniazid / Q000494:pharmacology*; D011817:Rabbits; D012156:Reticulocytes / Q000187:drug effects* / Q000378:metabolism
D000431:Ethanol; D006418:Heme; D002701:Chloramphenicol; D006427:Hemin; D005914:Globins; D007538:Isoniazid