Toxicology 230 (2007) 22–44 Modulating effects of dietary fats on methylmercury toxicity and distribution in rats Xiaolei Jin a , Eric Lok a , Genevieve Bondy a , Don Caldwell a , Rudi Mueller a , Kamla Kapal a , Cheryl Armstrong a , Marnie Taylor a , Stan Kubow c , Rekha Mehta a,∗ , Hing Man Chan b a Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Postal Locator 2204D2, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, Canada K1A 0L2 b Community Health Program, University of Northern British Columbia, 3333 University Way, Prince George, British Columbia, Canada V2N 4Z9 c School of Dietetics and Human Nutrition, McGill University, Montreal, Quebec, Canada H9X 3V9 Received 30 June 2006; received in revised form 14 September 2006; accepted 23 October 2006 Available online 20 December 2006 Abstract Fish consumption is the most important source of human exposure to methylmercury (MeHg). Since fish is also a rich source of n - 3 polyunsaturated fatty acids, this study was conducted to examine the effects of dietary fats on MeHg-induced acute toxicity in rats. Weanling male Sprague Dawley rats were administered semi-purified casein-based isocaloric diet containing soy oil, seal oil, docosahexaenoic acid (DHA), fish oil, or lard for 28 days. Rats were then gavaged with 0, 1, or 3 mg MeHg/kg body weight (BW) per day and fed the same diet for 14 consecutive days. On 43rd day of the experiment, rats were sacrificed and blood samples were collected and analyzed for hematology. Liver and spleen were removed, fixed, and examined for pathological changes. Blood, feces, liver, and brain were analyzed for total mercury and/or MeHg contents. Serum samples were analyzed for clinical markers of hepatic injury and immunoglobulin. Total mercury contents in all tissues measured increased with dose. Mercury excretion in feces increased with dose and duration of MeHg treatment. Both diets and MeHg showed significant effects and interacted significantly on many of the toxicological endpoints measured. Many of the effects of MeHg were diet-dependent. For example, in the rats fed the lard diet, 3 mg MeHg/kg BW significantly increased relative liver and spleen weight as compared with vehicle control; whereas in rats fed the fish oil, soy oil, seal oil, or DHA, this effect of MeHg was less obvious or absent, suggesting a protective effect of these diets. MeHg at 3 mg/kg BW significantly decreased serum albumin level in all except DHA dietary groups, implying a protection by the DHA diet on this parameter. Only in the lard dietary group, did 3 mg MeHg/kg BW significantly increase serum bilirubin level, indicating an enhancing effect of this diet on MeHg toxicity. MeHg suppressed the adaptive immune system and stimulated the innate immune system in rats in a diet-dependent fashion. The seal oil diet provided more resistance, while the fish oil diet rendered greater sensitivity to these effects of MeHg on the immune system. These results imply significant modulating effects of dietary fats on MeHg toxicity which may translate into more severe or protective clinical outcomes. Therefore, dietary fats are important factors to be considered in the risk assessment of MeHg exposure. Crown Copyright © 2006 Published by Elsevier Ireland Ltd. All rights reserved. Keywords: Methylmercury; Acute toxicity; Diets; Dietary fats; Serum biochemistry; Hematology; Immune system; Pathology ∗ Corresponding author. Tel.: +1 613 957 0988; fax: +1 613 941 6959. E-mail address: Rekha Mehta@hc-sc.gc.ca (R. Mehta). 0300-483X/$ – see front matter. Crown Copyright © 2006 Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.tox.2006.10.023