Enhancement of Lindane-induced Liver Oxidative Stress and Hepatotoxicity by Thyroid Hormone is Reduced by Gadolinium Chloride

Abstract

The role of Kupffer cells in the hepatocellular injury and oxidative stress induced by lindane (20 mg/kg; 24h) in hyperthyroid rats (daily doses of 0.1 mg L-3,3',5-triiodothyronine (T3)/kg for three consecutive days) was assessed by the simultaneous administration of gadolinium chloride (GdCl3; 2 doses of 10mg/kg on alternate days). Hyperthyroid animals treated with lindane exhibit enhanced liver microsomal superoxide radical (O2.-) production and NADPH cytochrome c reductase activity, with lower levels of cytochrome P450, superoxide dismutase (SOD) and catalase activity, and glutathione (GSH) content over control values. These changes are paralleled by a substantial increase in the lipid peroxidation potential of the liver and in the O2.- generation/ SOD activity ratio, thus evidencing a higher oxidative stress status that correlates with the development of liver injury characterized by neutrophil infiltration and necrosis. Kupffer cell inactivation by GdCl3 suppresses liver injury in lindane/T3-treated rats with normalization of altered oxidative stress-related parameters, excepting the reduction in the content of GSH and in catalase activity. It is concluded that lindane hepatotoxicity in hyperthyroid state, that comprises an enhancement in the oxidative stress status of the liver, is largely dependent on Kupffer cell function, which may involve generation of mediators leading to pro-oxidant and inflammatory processes.

Analysis of differentially expressed genes in hyperthyroid-induced hypertrophied heart by cDNA microarray

“…Furthermore an increased amount of lipid peroxidation (data not shown) and a decreased level and activity of SOD1 (Table 1, Figs 3A and B), in thyroid hormoneinduced rat heart indicates the occurrence of severe oxidative stress. Such a decrease in the level and activity of SOD due to increased oxidative stress has also been reported by others in a number of different experimental situations (Indik et al 2001, Simon-Giavarotti et al 2002. Thyroid hormone-induced hypermetabolism, involving all major fuel sources, is a hallmark of hyperthyroidism (Moller et al 1996).…”

Hypolipidemic Activity of Olive Oil (Olea europaea) against High Fat Diet-Induced Nonalcoholic Fatty Liver Disease (NAFLD) in Mice

“…Serum AST, ALT and ALP are the enzyme biomarkers to monitor the liver structural integrity and damage and aids in the clinical diagnosis of NAFLD and other liver toxicity conditions [47] [48]. Generally high-fat diet increases these enzymes through the induction of oxidative stress in the liver [48].…”

Regulation of oxidative stress and lipid peroxidation in PTU induced mice, treated with Pyrroloquinoline quinone (PQQ)

“…Liver is a major target organ for thyroid hormone with important biological and medical implications (Feng et al, 2000;Simon-Giavarotti et al, 2002). Clinical diagnosis of disease and damage to the structural integrity of liver is commonly assessed by monitoring the status of serum SGOT and SGPT activities (Amin and Hamza, 2005).…”