Dietary fats modulate methylmercury-mediated systemic oxidative stress and oxidative DNA damage in rats.
We examined the effects of dietary fats on methylmercury (MeHg)-induced systemic oxidative stress and oxidative DNA damage in liver and kidney of male Sprague-Dawley rats. Rats were treated with a casein-based purified isocaloric diet containing 15% by weight soy oil, docosahexaenoic acid (DHA), seal oil, fish oil, or lard for 28 days, and then gavaged with 0, 1, or 3 mg MeHg/kg BW/day for 14 days. Urine was analyzed for 8-hydroxydeoxyguanosine (8-OHdG) and isoprostane, and serum for total antioxidant capacity (TAC). Liver and kidney were analyzed immunohistochemically for 8-OHdG. Both diet and MeHg showed significant main effects on some of these markers. As compared with the vehicle control, 3 mg MeHg/kg BW significantly increased urinary 8-OHdG in the lard group, urinary isoprostane in the DHA, seal oil, and fish oil groups, while significantly decreasing serum TAC in the lard and fish oil groups. In all dietary groups, 8-OHdG positive staining was located mainly in the nuclei of various cell types in liver and kidney. MeHg expressed a significant main increasing effect on 8-OHdG-positive cells in kidney. These results suggest that both dietary fats and MeHg are important mediators of systemic oxidative stress and oxidative DNA damage.
Jin
Xiaolei
X
Toxicology Research Division, Food Directorate, HPFB, Health Canada, Ottawa, ON, Canada. Dawn_Jin@hc-sc.gc.ca
Chan
Hing Man
HM
Lok
Eric
E
Kapal
Kamla
K
Taylor
Marnie
M
Kubow
Stan
S
Mehta
Rekha
R
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008767:Methylmercury Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D015415:Biomarkers; D004041:Dietary Fats; D007202:Indicators and Reagents; D008767:Methylmercury Compounds; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine