Phenylhydrazine anemia

The mature red blood cell cannot synthesize protein. Reticulocytes are active in protein synthesis. Once reticulocytes enter the circulation, they lose their intracellular organelles (ribosomes, mitochondria, etc) within about 24 hours, becoming young red blood cells and concomitandy losing their ability to synthesize protein. Extracts of rabbit reticulocytes (obtained by injecting rabbits with a chemical—phenylhydrazine—that causes a severe hemolytic anemia, so that the red cells are almost completely replaced by reticulocytes) are widely used as an in vitro system for synthesizing proteins. Endogenous mRNAs present in these reticulocytes are destroyed by use of a nuclease, whose activity can be inhibited by addition of Ca +. The system is then pro-... 

Gelman et al. (1978) found that the interaction between lead and phenylhydrazine produced an additive effect in the acute hemolytic phase of anemia and a probable synergistic effect during the compensatory phase of anemia in rabbits. The mechanism postulated for anemic interaction appears to be primarily related to depressed bone marrow production of erythrocytes rather than to increased hemolysis. 

Toxieology. Phenylhydrazine causes hemolytic anemia and is a skin sensitizer in animals it has caused liver and kidney injury secondary to hemolytic anemia and is carcinogenic. 

Inhibition of immune hemolysis by berberine was described by Tanaka (505). Subcutaneous or intravenous injections of berberine either in single doses or repeatedly did not affect the number of erythrocytes, leukocytes, and the hemoglobin level of intact rabbits (506). In rabbits, with anemia induced by phenylhydrazine and toluenedia-mine, berberine had an antianemic effect. Hasegawa and Tanaka (507) did not observe any effect of berberine on the production of plasma cells. It decreased the anticoagulant action of heparin in dog and human blood in vitro (508). Morthland (509) carried out a spectrophotometric study of the interaction of nucleic acids with aminoacridine or with other basic stains including berberine. 

Naughton BA, Dornfest BS, Bush ME, Carlson, CA, Lapin DM. Immune activation is associated with phenylhydrazine-induced anemia in the rat. J Lab Chn Med 1990 116(4) 498-507. 

Phenylhydrazine caused adverse reproductive effect when dosed intraperitoneally in pregnant mice. It caused jaundice, anemia, and behavioral deficit in offspring. 

Phenylhydrazine (CAS 100-63-0) A strong base and corrosive upon direct contact. A potent skin sensitizer. Dermal absorption occurs. Vapors very irritating to eyes and respiratory tract. May cause hemolytic anemia with secondary kidney damage. Limited evidence of carcinogenicity in test animals. 0.1 ppm, S,A3 NIOSH CA 15 ppm 3 2 0 Pale yellow crystals or oily liquid with a weakly aromatic odor. Darkens upon exposure to air and light. Vapor pressure is less than 0.1 mm Hg at 20°C (68°F). Combustible. Thermal-breakdown products include oxides of nitrogen. 

Immature red blood cells contain free PROTO. The level of PROTO in the circulating erythrocytes is affected by a number of factors. In iron deficiency, or in anemia following hemorrhage, a high erythrocyte protoporphyrin (EP) is found of 20Q-400 itg per 100 cc. of erythrocytes as contrasted to normal values of 20-40 fig. EP is found to be high also in anemias of infectious nephritis and leukemia. It is low in pyridoxine and folic acid deficiencies (see 5-AL formation) (ISO). In acute lead poisoning of rabbits the EP is 500 fig. In phenylhydrazine poisoning the EP is 300 fig and COPRO is increased also (131). 

Erdos assayed his material for activity by noting its influence on tiie anemia produced in dogs and rabbits by the administration of phenyl-hydrazine (33). In the normal animal, the administration of phenyl-hydrazine hydrochloride (16 mg. per kg. body Aveight) lowered the red cell count 25 to 40 per cent in 48 to 72 hours, after Avhich time, spontaneous remission occurred. HoAvever, in those animals Avhich received liver preparations along Avith the phenylhydrazine, the ma, imal decrease of red cells Avas reached only after 96 to 120 hours. 

Our own studies on mRNA and hemoglobin synthesis have been carried out primarily in duck erythroblasts. Earher studies in duck erythrocytes had indicated the usefulness of this system for the study of heme and globin synthesis (Shemin et al., 1948 Kassenaar et at, 1957). By inducing profound hemolytic anemia in ducks with acetyl-phenylhydrazine, one can obtain in the peripheral blood very immature erythroblasts with a strikingly increased capacity for the synthesis of RNA and protein. Studies begun in collaboration with Gros and subsequently extended by Scherrer et al. (1966a,b) will be summarized briefly. 

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