European Journal of Experimental Biology Libre accès

Abstrait

Toxicity assessment of Linezolid and the beneficial effects of human erythropoietin in mice

Muqtedar Iftekhar Patel* and Surinder J. Makhija

Linezolid (LZD), an antibiotic launched in year 2000, but due to its bone marrow toxicity which results in to thrombocytopenia and red cell anemia, the market size is narrowed. The mechanism of such toxicity is still not very clear, so the present work focused to investigate the possible mechanism of bone marrow toxicity in progenitors of red blood cells and its treatment by using erythropoietin (EPO). Male albino mice administered doses of 100 and 200 mg/kg two times a day with 6 hours of interval, for 19 and 9 days, respectively. And beneficial effects of erythropoietin (EPO) were investigated. The results demonstrated that sensitive parameters of red cell anemia like PCE: NCE ratio and % retics were significantly decreased. Treatment of EPO resulted into stimulation of erythropoiesis in LZD exposed animals. At 100 mg/kg dose, increase in PCE: NCE ratio and % retics in EPO injected animals was significant as compared to stand alone LZD administered animals (p<0.001). There was also significant increase in RBC and HGB in same group due to EPO injection (p<0.05). These results give the evidence that LZD targeted precursor cells CFU-E, BFU-E and Erythroblasts in bone marrow and induced the conditions like red cell anemia. And plays beneficial role and stimulated the erythropoiesis in bone marrow to normalize the condition in mice. Therefore, this short term model can be used to fasten the screening of newer oxazolidinones class of antibiotics for bone marrow toxicity and the beneficial effects of EPO also can be screened.