Mechanism of haematotoxicity induced by phenylhydrazine: a review


  • Shwetha B R Mallige College of Pharmacy, Department of Pharmacology, Silvepura, Bangalore-90
  • Siddalingaprasad H S Department of Studies and Research in Biochemistry, Tumkur University, Tumakuru- 572103
  • Shivukumar Swamy Mallige College of Pharmacy, Department of Pharmacology, Silvepura, Bangalore-90
  • Nagalakshmi N C Mallige College of Pharmacy, Department of Pharmacology, Silvepura, Bangalore-90
  • Hariprasad M G Mallige College of Pharmacy, Department of Pharmacology, Silvepura, Bangalore-90


Haemolytic anaemia, Erythropoietin receptors, Phenylhydrazine, Haematotoxicity


This work was carried out to show the effects of phenylhydrazine (PHZ) induced anaemic condition. Anaemic condition is defined as reduction in red blood cells (RBC) than normal number of red blood cells. The anti-anaemic activity can be studied using the changes in haematological parameters (PCV, RBC & Haemoglobin) influenced by PHZ [(40mg/kg p.o.)] in rats. PHZ, a potent chemical that causes different effects on different tissues at several levels. Administration of PHZ causes haemolytic anaemia, genotoxic effects and rose in iron absorption in spleen, liver and duodenum & causes change in iron metabolism. PHZ acts by activating immune response which triggers phagocytosis and also interfere with the binding of erythropoietin (EPO) receptors and further JAK-STAT pathway. PHZ also causes genotoxic effect by forming single strand DNA damage. In view of lipid peroxidation along with the formation of Thiobarbituric acid (TBA)-reactive malonyldialdehyde, it is recommend that PHZ induces anaemia as an outcome of peroxidation of  RBC membrane lipids and this effect may be a upshot of the autoxidation of the drug and the interaction of membrane lipids and oxygen radicals


Download data is not yet available.


Turaskar A, More S, Sheikh R, Gadhpayle J, Bhongade SL, Shende V. Antianaemic potential of Swertia chirata on phenylhydrazine induced reticulocytosis in rats. American Journal of Phytomedicine and Clinical Therapeutics, 1, 37-41 (2013)

Luka C D, Abdulkarim M, Adoga G I, Tijjani H & Olatunde A. Anti-anaemic potential of aqueous extract of Spinacia oleracea leaf in phenyhydrazine-treated rats. NY Sci J, 7(6), 14-18 (2014)

Gupta D, Kushwah C, Joshi A, Malviya S, Kharia A. Anti-anemic activity of hydroalcoholic extract of leaves of LyciumBarbarum in phenylhydrazine induced anemic rats. International Journal of Research in Pharmaceutical Sciences, 8(2), 1-3 (2018)

Falconer E. Treatment of polycythemia: the reticulocyte response to venesection, phenylhydrazine and radiation. Annals of Internal Medicine, 7, 172-189 (1933)

Magnani M, Stocchi V, Chiarantini L, Chiarantini L and fornaini G. Red blood cells phagocytosis and lysis following oxidative damage by phenylhydrazine. Cell Biochemistry and Function, 4, 263-269 (1986)

Types of anemia. Available from:


Duff S. Types of Anaemia.

Dada L, Gladys O, McKie AT, Simpson RJ. Animal models with enhanced erythropoiesis and iron absorption. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1762(4), 414-423 (2006)

World Health Organization. Worldwide prevalence of anaemia 1993–2005. Geneva: World Health Organization. ISBN,

Bigoniya P, Singh S, Singh C S, Shukla A. Anti-anemic potential estimation on mice and characterization of flavonoids using high performance thin layer chromatography in Wrightia tinctoria bark fraction. Journal of Natural Pharmaceuticals, 4(1), 47 (2013)

Latunde- Dada GO, Vulpe CD, Anderson G J, Simpson RJ, McKie AT. Tissue-specific changes in iron metabolism genes in mice following phenylhydrazine-induced haemolysis. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1690, 2, 169-176 (2004)

Raja KB, Simpson RJ, Peters TJ. Effect of exchange transfusion of reticulocytes on in vitro and in vivo intestinal iron (Fe3+) absorption in mice. British journal of haematology, 73(2), 254-259 (1989)

McKie AT, Barrow D, Latunde-Dada GO, Rolfs A, Sager G, Mudaly E, Peters TJ. An iron-regulated ferric reductase associated with the absorption of dietary iron. Science, 291(5509), 1755-1759 (2001)

Maines MD. The hemeoxygenase system: A regulator of second messenger gases. Annual Review toxicology, 37, 517-554 (1997)

Jiang X, Gao M, Chen Y, Liu J, Qi S, Ma J, Xu Y. EPO-dependent induction of erythroferrone drives hepcidin suppression and systematic iron absorption under phenylhydrazine-induced hemolytic anemia. Blood Cells, Molecules, and Diseases, 58, 45-51 (2016)

Rifkind. Heinz body anaemia: an ultrastructural study II- Red cell sequestration and destruction. Blood, 26, 433-448 (1965)

Rifkind RA, Danon D. Heinz Body anaemia: An ultrastructural study I- Heinz Body formation. Blood, 100, 4272-4290 (2002)

McMillan DC, Jensen CB, Jollow DJ. Role of lipid peroxidation in dapsone-induced hemolytic anemia. Journal of Pharmacology and Experimental Therapeutics, 287(3), 868-876 (1998)

Pandey K, Meena AK, Jain A, Singh RK. Molecular mechanism of phenylhydrazine induced haematotoxicity: A review. Ame J Phytomed Clin Therapeut, 2, 390-394 (2014)

Parodi S, De Flora S, Cavanna M, Pino A, Robbiano L, Bennicelli C, Brambilla G. DNA-damaging activity in vivo and bacterial mutagenicity of sixteen hydrazine derivatives as related quantitatively to their carcinogenicity. Cancer research, 41(4), 1469-1482 (1981)

Brennan RJ, Swoboda BE, Schiest RH. Oxidative mutagens induce intrachromosomal recombination in yeast. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 308(2), 159-167 (1994)

Ferrali M, Signorini C, Sugherini L, Pompella A, Maura L, Caciotti B, Ciccoli L, Comporti M. Release of free redoxdoxactive iron in the liver and DNA oxidative damage following PHZ intoxication. Biochemical pharmacology, 53(11), 1743-1751 (1997)

Spivak JL. Polycythemia vera: myths, mechanisms, and management. The Journal of the American Society of Hematology, 100(13), 4272-4290 (2002)

Olinescu R, Alexandrescu R, Hulea SA, Kummerow FA. Tissue lipid peroxidation may be triggered by increased formation of bilirubin in vivo. Research communications in chemical pathology and pharmacology, 84(1), 27-34 (1994)

Stevens MA. Use of the albino guinea-pig to detect the skin-sensitizing ability of chemicals. Occupational and Environmental Medicine, 24(3), 189-202 (1967)

Dornfest BS, Naughton BA, Johnson R, Gordon AS. Hepatic production of erythropoietin in a phenylhydrazine- induced compensated hemolytic state in the rat. The Journal of laboratory and clinical medicine, 102(2), 260-273 (1983)

Brennan R J, Swoboda BEP, Schiestl R H. Oxidative mutagens induce intrachromosomal recombination in yeast. Mutant Res, 308, 159-167 (1994)

Rothe A. Contact dermatitis from N-(alpha-chlorobenzylidene) phenylhydrazine. Contact Dermatitis, 18, 16-19 (1988)

Cary R, Dobson S, Brooke I,WHO,,/entity/ipcs/publications/cicad/en/cicad19.pdf

Aguwa C N. Therapeutic basis of clinical pharmacy in the tropics. (2nd edition), Uptimal publications, enugu Nigeria, 379-381 (1996)

Khandewal K R. Practical pharmacognosy. (14th ed), Nirali Prakashan, pune, 2005

Suzuki Y, Shimizu H. A sensitive micronucleus test in vitro with the use of cultured bone- marrow cells. Mutation Research/Environmental Mutagenesis and Related Subjects, 130(5), 382 (1984)

Pankey K, Meena AK, Jain A, Singh RK. Molecular mechanism of phenylhydrazine induced haematotoxicity: A Review. American J of Phytomedicine and Clinical Therapeutics, 2(3), 390-394 (2014)



How to Cite

Shwetha, B. R., Siddalingaprasad, . H. S., Swamy, S., Nagalakshmi , N. C., & Hariprasad, M. G. (2019). Mechanism of haematotoxicity induced by phenylhydrazine: a review. Journal of Applied Pharmaceutical Research, 7(4), 01-06. Retrieved from