Effects of acute lindane intoxication and thyroid hormone administration in relation to nuclear factor-κB activation, tumor necrosis factor-α expression, and Kupffer cell function in the rat

Nuclear factor-kappaB (NF-kappaB) DNA binding, tumor necrosis factor-alpha (TNF-alpha) 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 (T-3) (0.1 mg T-3/kg) and/or lindane (50 mg/kg; 4h after T-3). Liver NF-kappaB DNA binding and serum TNF-alpha levels were enhanced by the combined T-3-lindane administration after 16-22 h, effects that were lower than those elicited by the separate treatments and coincided with increased hepatic TNF-alpha rnRNA levels. Thyroid calorigenesis occurred independently of lindane, whereas T-3, lindane and T-3-lindane groups showed liver glutathione (GSH) depletion, with higher protein carbonyl levels in lindane and T-3-lindane groups. Carbon-induced O-2 consumption/carbon uptake ratios were not altered by T-3 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 T-3- or lindane-induced liver NF-kappaB activation and TNF-alpha 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. (C) 2004 Elsevier Ireland Ltd. All rights reserved.