Iron-induced changes in nitric oxide and superoxide radical generation in rat liver after lindane or thyroid hormone treatment

The involvement of cytosolic nitric oxide (NO) and mitochondrial superoxide radical (O-2(.-)) production was evaluated as a mechanism triggering liver oxidative stress in lindane (40 mg/kg) or L-3,3',5-triiodothyronine (T-3, 0.1 mg/kg for 2 consecutive days) treated animals (male Sprague-Dawley rats ) subjected to iron overload (200 mg/kg). Lindane and iron led to 504 and 2 10% increases in the content of hepatic protein carbonyls as an index of ox idative stress, with a 706% enhancement being produced by their combined ad ministration. T-3 did not alter this parameter, whereas iron overload incre ased the content of protein carbonyls by 116% in hyperthyroid rats. Lindane increased NO generation by 106% without changes in generation of O-2(.-), whereas iron enhanced both parameters by 109 and 80% over control values, r espectively, with a net 33 and 46% decrease, respectively, being elicited b y the combined treatment related to iron overload alone. Hyperthyroidism in creased liver NO (69%) and O-2(.-) (110%) generation compared to controls, effects that were either synergistically augmented or suppressed by iron ov erload, respectively. The in vitro addition of iron (1 mu mol/mg protein) t o liver cytosolic fractions from euthyroid (97%) and hyperthyroid (173%) ra ts also enhanced NO generation. The effects of iron overload on mitochondri al O-2(.-) production by hyperthyroid rats were reproduced by the in vitro addition of 1 mu mol iron/mg protein and abolished by the in vivo pretreatm ent with the iron chelator desferrioxamine (500 mg/kg). It is concluded tha t liver oxidative stress induced by iron overload is independent of NO and O-2(.-) production in lindane-treated rats, whereas in hyperthyroid animals NO generation is a major factor contributing to this redox imbalance. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.