Fumonisin B-1-induced DNA damage in rat liver and spleen: Effects of pretreatment with coenzyme Q(10), L-carnitine, alpha-tocopherol and selenium

Active oxygen radical species are reported to cause organ damage. This stud y was designed to determine whether oxidative stress contributed to the ini tiation or progression of hepatic and splenic cell DNA damage induced by fu monisin B-1 (FB1) in rats. Another aim was to investigate the protective ef fects 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 si ngle dose of fumonisin B-1 at 1.55 mg kg(-1) body wt. into the tail vein. T reatment with FB, led to splenic and hepatic DNA fragmentation in 85% of th e test animals. DNA fragmentation was investigated as a critical event in t oxic cell death by testing total Ca2+ in liver. FB, administration caused t otal 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 sple nic 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) die t), alpha-tocopherol (30 IU vitamin E kg(-1) diet) and selenium (1 mg selen ium as sodium selenite kg(-1) diet), decreased DNA damage and the activitie s 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 aga inst toxic cell death and glutathione depletion caused by FB1. Oxidative da mage caused by FB1 may be one of the underlining mechanisms of FB1-induced cell injury and DNA damage. (C) 1999 Academic Press.