Dietary fats altered nephrotoxicity profile of methylmercury in rats.
Weanling male Sprague-Dawley rats were administered semi-purified isocaloric diet containing soy oil (SO), seal oil (SE), docosahexaenoic acid (DHA), fish oil (FO) or lard (LA) for 28 days, and then gavaged with 0, 1 or 3 mg MeHg kg(-1) body weight per day and fed the same diet for 14 days. Serum and 24 h urine samples were collected on the day of necropsy, and analyzed for markers of kidney function and diseases. Kidney slices were analyzed for para-amino-hippurate (PAH) and tetraethylammonium (TEA) uptake, total mercury and MeHg content, and examined for pathological lesions. Total mercury and MeHg contents increased significantly and dose-dependently in all dietary groups. MeHg significantly increased relative kidney weight in all groups, serum creatinine in all except SO group, serum uric acid in the DHA and LA groups, serum Mg in all except the LA group, and urinary protein in the SO group. MeHg significantly decreased serum urea nitrogen in SE, FO and LA groups, urinary creatinine in the DHA group, PAH uptake in all except the SE group, and TEA uptake in all groups. MeHg caused nephrosis in all dietary groups. MeHg also significantly increased neutrophil counts in all except the SE group, decreased serum albumin and triglyceride in all except the DHA group, and increased serum total cholesterol in all groups, suggesting a nephrotic syndrome-like outcome. These results confirmed that kidney tubules are major targets of MeHg nephrotoxicity. Treatment with dietary fats did not prevent, but rather altered the profile of, nephrotoxicity of MeHg in rats.
Jin
Xiaolei
X
Toxicology Research Division, Food Directorate, HPFB, Health Canada, Ottawa, Ontario K1A0L2, Canada. Dawn_Jin@hc-sc.gc.ca
Lok
Eric
E
Caldwell
Don
D
Mueller
Rudi
R
Kapal
Kamla
K
Liston
Virginia
V
Kubow
Stan
S
Chan
Hing Man
HM
Mehta
Rekha
R
D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000097:blood; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood / Q000652:urine; D004032:Diet; D004041:Dietary Fats / Q000145:classification / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008274:Magnesium / Q000097:blood; D008297:Male; D008657:Metabolic Clearance Rate; D008767:Methylmercury Compounds / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D009401:Nephrosis / Q000139:chemically induced / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D009994:Osmolar Concentration; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014527:Uric Acid / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000652:urine; D010130:p-Aminohippuric Acid / Q000378:metabolism
D004041:Dietary Fats; D008767:Methylmercury Compounds; D000644:Quaternary Ammonium Compounds; D012709:Serum Albumin; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D014527:Uric Acid; D002784:Cholesterol; D003404:Creatinine; D005723:gamma-Glutamyltransferase; C027917:tetramethylammonium; D008274:Magnesium; D002118:Calcium; D010130:p-Aminohippuric Acid