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Pathology of "Toxic Oils" and Selected Metals in the MRL/lpr Mouse

College of Veterinary Medicine, Oregon State University, Corvallis, Oregon 97331

Bernadette V. Stang

College of Veterinary Medicine, Oregon State University, Corvallis, Oregon 97331

Manuel Posada de la Paz

Centro de Investigación sobre el Síndrome del Aceite Tóxico, Instituto de Salud Carlos -C/Sinesio Delgado, 6-28029-Madrid, Spain

Maria V. Ruiz Mendez

Instituto de las Grasa. C.S.I.C., Avda. P. García Tejero, 4-41012 Sevilla, Spain

The Toxic Oil Syndrome epidemic that occurred in Spain in 1981 and affected nearly 20,000 people was caused by ingestion of oil mixtures that contained analine-denatured rapeseed oil. To date, an animal model in which to identify the actual etiologic agents(s) and to investigate the pathogenesi s of the disease has not been discovered. In this study, the MRL/lpr was used to assess the histopathological response of 3 "toxic oils" and 3 metals. The oils tested were a denatured rapeseed oil collected from a family who were affected by the Toxic Oil Syndrome epidemic in Spain (CO756) plus two synthesized oils (RSD and RSA). Female mice, 7 weeks of age, received an undiluted (neat) or a 1:10 diluted dose of each oil; mercury (50 ppm), cadmium (100 ppm), or lead (50 ppm). Half of each group was killed after 5 weeks of exposure and the remaining mice after 10 weeks of exposure. Body and organ weights (liver, kidney, thymus, and spleen) were recorded and selected organs were collected for histopathology. Ten weeks after treatment, body weights (BW) of the cadmium and lead groups were signifi cantly suppressed, and the body weight of the CO756-neat group was signifi cantly increased compared to their respective controls. Kidney/BW were decreased in the RSA-neat and RSA 1:10 groups after 10 weeks of exposure, and the kidney/BW in the mercury and cadmium groups were increased. Spontaneous development (12 weeks of age) and progression (17 weeks of age) of histopathological lesions are described for selected organs examined in the naïve mice as are changes that resulted from exposure to the "toxic oils" and metals. CO756-neat, mercury, and lead suppressed progression of the glomerulonephriti s that normally occurs in the MRL/lpr mouse. Also of interest were lesions that included mononuclear cuffi ng of hepatic bile ducts, progression of the granuloma s that formed in the renal glomeruli, vessels in the lymphoid organs that contained tightly packed lymphocytes, and the presence of plasma cells in the thymus. All 3 oils stimulated early development of the lymphoproliferative syndrome characteristic of the MRL/lpr mouse as demonstrated by an increase in the thymus/BW and spleen/BW ratios after 5 weeks of treatment. These data contribute to our knowledge of spontaneou s disease progression in the thymus, spleen, lymph nodes, and kidneys in the MRL/lpr mouse and the effects of 3 different "toxic oils" and metals on the development and progression of those lesions.

Key Words: Autoimmune disease • Toxic Oil Syndrome • mercury • cadmium • lead • glomerulonephritis • lymphoproliferation • MRL/lpr mice.

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Toxicologic Pathology, Vol. 29, No. 6, 630-638 (2001)
DOI: 10.1080/019262301753385960


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