Developmental exposure to diuron causes splenotoxicity in male Sprague-Dawley rat pups

Abstract

This study investigated whether perinatal exposure to diuron [3-(3,4-dichlorophenyl)-1-1-dimethylurea] might exert adverse effects on rat lymphoid organs. Pregnant Sprague-Dawley (SD) rats were exposed to diuron at 500, 750 or 1250 ppm in the diet from gestational days (GD) 12–21 and during lactation. At postnatal day (PND) 42, male pups were euthanized and thymus, spleen, mesenteric lymph node and femur were collected for histopathological analysis. Food consumption and body weight gain were significantly reduced in dams exposed to 1250 ppm during gestation period. Also, Diuron at 750 and 1250 ppm produced: (1) increased relative spleen weight associated histologically with severe congestion in red pulp, (2) enhanced extramedullary hematopoiesis and hemosiderosis as well as (3) depletion of lymphoid follicles in white pulp. Flow cytometric analysis revealed a significant reduction in B lymphocytes (CD45RA+) in male pups but T lymphocytes (CD4+, CD8+ and CD4+/CD8+) were not markedly affected. Thus, data suggest that Diuron-induced maternal toxicity in dams exposed to high dose and perinatal exposure to this herbicide produced spleen toxicity as evidenced by a reduction in B lymphocyte number in male SD pups.

Keywords:

• Gestation
• lactation
• diuron
• lymphoid organs
• postnatal life

Acknowledgments

This study was supported by grants from FAPESP, CAPES and CNPq. The authors would like to thank Dr. João Lauro Viana de Camargo, Senior Researcher and Supervisor of the TOXICAM laboratory (Botucatu Medical School, São Paulo State University), and also Paulo C. Georgete and Paulo R. Cardoso for their technical support. Domingues, A. and Grassi, T. F. were recipients of a fellowship from FAPESP (2005/01223-7 and 2006/01330-0, respectively).

Notes

¹Values are mean ± SD; ²500, 750 or 1250 ppm of diuron in basal diet during perinatal period.

²Number of animals.

*Different from G1 group, P ≤ 0.01.

¹500, 750 or 1250 ppm of diuron in basal diet during perinatal period; ² Number of pup male/group;

*Different from G1 group (0.03 < P < 0.001).