Abstract

Nuclear factor-?B (NF-?B) DNA binding, tumor necrosis factor-? (TNF-?) expression, and parameters related to liver oxidative stress and Kupffer cell function were assessed in control rats and in animals given 3,3?,5-triiodothyronine (T3) (0.1mg T 3/kg) and/or lindane (50mg/kg; 4h after T3). Liver NF-?B DNA binding and serum TNF-? levels were enhanced by the combined T3-lindane administration after 16-22h, effects that were lower than those elicited by the separate treatments and coincided with increased hepatic TNF-? mRNA levels. Thyroid calorigenesis occurred independently of lindane, whereas T3, lindane and T 3-lindane groups showed liver glutathione (GSH) depletion, with higher protein carbonyl levels in lindane and T3-lindane groups. Carbon-induced O2 consumption/carbon uptake ratios were not altered by T3 or lindane compared to controls, whereas combined T 3-lindane administration elicited a 92% diminution with enhancement in the sinusoidal efflux of lactate dehydrogenase (LDH). In conclusion, depression of T3- or lindane-induced liver NF-?B activation and TNF-? expression occurred after their combined treatment, effects that correlate with the impairment of the respiratory burst activity of Kupffer cells and exacerbation of liver injury. © 2004 Elsevier Ireland Ltd. All rights reserved.