<i>p</i>,<i>p</i>′-DDT induces microcytic anemia in rats

Abstract

Emerging evidence suggests that chronic exposure to DDT and its derivatives is associated with a variety of human disorders such as anemia. The present study demonstrated that p,p'-DDT caused microcystic anemia in a dose-dependent manner (0, 5, 50, and 500 ppm) in the long-term study up to 2 years. To elucidate the mechanism(s) by which p,p'-DDT induces anemia, certain hematological parameters were assessed in rats fed specific doses of p,p'-DDT for 2 weeks, and the effect of lipopolysaccharide on anemia of inflammation was also examined in p,p'-DDT-treated rats. The parameters included the content of hemoglobin per reticulocyte, mean corpuscular volume of reticulocytes and mature erythrocytes, corpuscular hemoglobin concentration mean of mature erythrocytes, and saturation levels of transferrin and iron. During the 2-week treatment period, hypochromic microcytic reticulocytes and hypochromic normocytic mature erythrocytes were observed in p,p'-DDT-treated rats, with no evidence of alteration in plasma iron levels. p,p'-DDT enhanced microcytosis of reticulocytes, as well as mature erythrocytes, which occurred due to severe hypoferremia resulting from anemia of inflammation; however, plasma iron levels were attenuated probably through the inhibition of interleukin-6. Our data suggests that long-term treatment with p,p'-DDT induces microcytic anemia, possibly because of the impairment of iron utility in erythrocytes.

Occupational exposure to pesticides and hematological alterations: A survey of farm residents in the South of Brazil

“…Animal studies have shown that persistent organochlorine (OC) pesticides can affect the hematopoietic system through oxidative stress and immunological mechanisms inducing apoptosis of mononuclear cells from peripheral blood 6 . According to this hypothesis, findings from some human studies support the existence of a relationship between environmental and occupational exposure to OC pesticides and blood disorders, particularly aplastic anemia [7][8][9][10][11][12][13][14] .…”

Safe long-term therapy of Cushing’s syndrome over 37 years with mitotane

“…A remarkable aspect of our patient’s history is that she repeatedly developed severe anemia, which resolved within a few weeks after the withdrawal of mitotane. Even if rarely reported, observations from animals exposed to DDT isomers suggest a causal relationship, possibly due to inflammation-associated hypoferremia, inhibition of hematopoietic tissue, or an estrogenic inhibitory effect on red blood cells ( 15 , 36 , 37 ).…”

KALGAE™ (Klebsormidium flaccidum var. ZIVO) dried algal biomass - 90-day dietary toxicity study and genotoxicity studies

“…There is no relationship between anisocytosis and MCV, as variation in the size of RBCs may occur for all values of MCV [ 18 ]. Tomita et al [ 20 ] reported that a 2-year dietary treatment with p,p ’-DDT resulted in microcytic anemia in rats as supported by significant decreases in HCT, HGB, RBC, MCV, and MCH after 12-weeks of treatment and significant decreases in HCT, HGB, MCV, and MCH after 26, 52, and 78 weeks of treatment. As shown in Table 2 (male) and Table 3 (female), there were no statistically significant changes reported in rats in either RBC or HGB at any of the doses tested, as well as in MCV or MCHC, supporting that the changes in MCH and RDW alone are not indicative of anemia or of toxicological significance in this study.…”