Fumonisin B1-induced DNA damage in rat liver and spleen: effects of pretreatment with coenzyme Q10, L-carnitine, alpha-tocopherol and selenium.
Active oxygen radical species are reported to cause organ damage. This study was designed to determine whether oxidative stress contributed to the initiation or progression of hepatic and splenic cell DNA damage induced by fumonisin B1 (FB1) in rats. Another aim was to investigate the protective effects of the antioxidants coenzyme Q10 (CoQ10), L-carnitine, vitamin E (alpha-tocopherol) and selenium against DNA damage in the liver and spleen of rats treated with FB1. Fasted rats were injected intravenously with a single dose of fumonisin B1 at 1.55 mg kg-1 body wt. into the tail vein. Treatment with FB1 led to splenic and hepatic DNA fragmentation in 85% of the test animals. DNA fragmentation was investigated as a critical event in toxic cell death by testing total Ca2+ in liver. FB1 administration caused total Ca2+ in liver to increase within 4 h (204% of control). Measurement of liver enzyme activities showed an increase in aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT). FB1 also markedly decreased splenic and hepatic glutathione (GSH) levels. Pretreatment with CoQ10 (30 mg CoQ10 kg-1 diet) together with L-carnitine (2.8 mg carnitine kg-1 diet), alpha-tocopherol (30 IU vitamin E kg-1 diet) and selenium (1 mg selenium as sodium selenite kg-1 diet), decreased DNA damage and the activities of Ca2+, ASAT and ALAT in the liver. On the other hand, the level of GSH was slightly increased. The CoQ10 alone did not significantly protect against toxic cell death and glutathione depletion caused by FB1. Oxidative damage caused by FB1 may be one of the underlining mechanisms of FB1-induced cell injury and DNA damage.
Atroshi
F
F
Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Helsinki, Finland.
Rizzo
A
A
Biese
I
I
Veijalainen
P
P
Saloniemi
H
H
Sankari
S
S
Andersson
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002264:Carboxylic Acids / Q000633:toxicity*; D002331:Carnitine / Q000494:pharmacology*; D003067:Coenzymes; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D037341:Fumonisins; D005978:Glutathione / Q000032:analysis; D008099:Liver / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology*
D002264:Carboxylic Acids; D003067:Coenzymes; D037341:Fumonisins; D014451:Ubiquinone; D014810:Vitamin E; C056933:fumonisin B1; D004247:DNA; C024989:coenzyme Q10; D005978:Glutathione; D012643:Selenium; D002331:Carnitine; D002118:Calcium