Dietary effects on xenobiotic-induced oxidative damage in ‘O’ group plaice

Larval and O-group flatfish such as flounder, plaice, sole and turbot live in subtidal inshore environments where they are not only subjected to elevated levels of natural oxidative stressors (e.g. UV radiation and hydrogen peroxide), but may also be exposed to xenobiotic chemicals which promote free radical formation and oxidative damage to cellularmacromolecules. These stressors may also cause damage to essential dietary lipid and deplete levels of the dietary antioxidant, vitamin E. Six-month-old plaice were reared for 3 months on three highly unsaturated fatty acids (HUFA)-sufficient artificial diets, one was vitamin E replete (250 mg/kg), and two were vitamin E-deficient (2–5 mg/kg). The HUFA in one of the latter were peroxidised before formulation and this resulted in lower hepatic HUFA levels. Whilst vitamin E-deficient fish had six-fold lower hepatic vitamin E levels, no changes in the microsomal lipid peroxidation products malondialdehyde (MDA) or 4-hydroxynon-enal (4HNE) were observed which may be attributable to an observed elevation in aldoketoreductase (AR), Cu/Zn superoxide dismutase (czSOD), glutathione S-transferase (GST-T) and glutathione reductase (GR) activities. Cellular GSH levels were reduced in the group fed the oxidised HUFA, vitamin E deficient diet which may be a consequence of the lack of enzyme induction and reduced catalase activity observed. After challenge of vitamin E-replete and –deficient fish for 48 h with hydrogen peroxide, an oxidative stressor producing superoxide, there was a decrease in catalase activity and cellular GSH levels were reduced despite a two-fold induction of GR activities. Microsomal MDA and 4HNE concentrations were lower than controls even though GST activities were lower. SOD activities were reduced in the deficient fish. After challenge with carbon tetrachloride, a stressor that is metabolised by the CYP-450 system to produce a C-centred free radical, which will attack HUFA, there was a reduction in GST activity and microsomal 4HNE concentrations were elevated. Se-dependent glutathione peroxidase and catalase activities were reduced in the vitamin E replete fish and all enzyme activities in the vitamin E-deficient fish after CCl4 challenge. Cellular GSH levels were reduced in both groups. These results show that activities of hepatic antioxidant enzymes can be modulated by oxidative stresses not only induced by xenobiotic exposure but by altered dietary antioxidant (vitamin E) status and that the cellular consequences are a complex interplay of these factors.