Effects of acute lindane intoxication and thyroid hormone administration in relation to nuclear factor-kappaB activation, tumor necrosis factor-alpha 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 (T3) (0.1 mg T3/kg) and/or lindane (50 mg/kg; 4 h after T3). Liver NF-kappaB DNA binding and serum TNF-alpha levels were enhanced by the combined T3-lindane administration after 16-22 h, effects that were lower than those elicited by the separate treatments and coincided with increased hepatic TNF-alpha mRNA levels. Thyroid calorigenesis occurred independently of lindane, whereas T3, lindane and T3-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 T3-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-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.
Valencia
César
C
Program of Molecular and Clinical Pharmacology, Faculty of Medicine, Institute of Biomedical Sciences, University of Chile, Casilla 70000, Santiago 7, Chile.
Cornejo
Pamela
P
Romanque
Pamela
P
Tapia
Gladys
G
Varela
Patricia
P
Videla
Luis A
LA
Fernández
Virginia
V
D000818:Animals; D018736:DNA Adducts; D005260:Female; D001556:Hexachlorocyclohexane / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D007728:Kupffer Cells / Q000187:drug effects* / Q000502:physiology*; D016328:NF-kappa B / Q000494:pharmacology*; D018384:Oxidative Stress; D010101:Oxygen Consumption; D051381:Rats; D017207:Rats, Sprague-Dawley; D014285:Triiodothyronine, Reverse / Q000008:administration & dosage / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D018736:DNA Adducts; D007306:Insecticides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014285:Triiodothyronine, Reverse; D001556:Hexachlorocyclohexane