title: Modulating effects of dietary fats on methylmercury toxicity and distribution in rats.
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, 3mg 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 3mg/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 3mg 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.
authors.affiliation: Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Jin
authors.forename: Eric
authors.initials: E
authors.lastname: Lok
authors.forename: Genevieve
authors.initials: G
authors.lastname: Bondy
authors.forename: Don
authors.initials: D
authors.lastname: Caldwell
authors.forename: Rudi
authors.initials: R
authors.lastname: Mueller
authors.forename: Kamla
authors.initials: K
authors.lastname: Kapal
authors.forename: Cheryl
authors.initials: C
authors.lastname: Armstrong
authors.forename: Marnie
authors.initials: M
authors.lastname: Taylor
authors.forename: Stan
authors.initials: S
authors.lastname: Kubow
authors.forename: Rekha
authors.initials: R
authors.lastname: Mehta
authors.forename: Hing Man
authors.initials: HM
authors.lastname: Chan
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D004435:Eating; D004906:Erythrocyte Count; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology; D005243:Feces / Q000737:chemistry; D005395:Fish Oils / Q000494:pharmacology; D006128:Growth / Q000187:drug effects; D007136:Immunoglobulins / Q000378:metabolism; D007958:Leukocyte Count; D008054:Lipid Peroxides / Q000737:chemistry; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008630:Mercury Poisoning / Q000473:pathology; D008767:Methylmercury Compounds / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D009821:Oils / Q000737:chemistry / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010976:Platelet Count; D051381:Rats; D017207:Rats, Sprague-Dawley; D046048:Seals, Earless; D013024:Soybean Oil / Q000494:pharmacology; D013154:Spleen / Q000473:pathology; D014018:Tissue Distribution; D014810:Vitamin E / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D005395:Fish Oils; D007136:Immunoglobulins; D008054:Lipid Peroxides; D008767:Methylmercury Compounds; D009821:Oils; D014810:Vitamin E; D013024:Soybean Oil