Fumonisin B1-induced DNA damage in rat liver and spleen:: Effects of pretreatment with coenzyme Q10, L-carnitine, α-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 B-1 (FB1) in rats. Another aim was to investigate the protective effects of the antioxidants coenzyme Q(10) (CoQ(10)), 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 B-1 at 1.55 mg kg(-1) body wt. into the tail vein. Treatment with FB, 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. FB, 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 CoQ(10) (30 mg CoQ(10) 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 CoQ(10) 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. (C) 1999 Academic Press.