The amount of a chemical (usually restricted to pesticides and food additives) that can be ingested daily, by humans, for an entire life-time without causing appreciable adverse effects.
Male rats are susceptible to chemically induced renal toxicity involving alpha2µ-globulin, a protein of 162 amino acids that is synthesized in the liver and released into the blood. Like other low-molecular weight proteins, the globulin is taken up by tubular epithelial cells and hydrolyzed in lysosomes. A large body of data shows that certain chemicals bind to the alpha2µ-globulin and interfere with catabolism, leading to accumulation of chemical-alpha2µ complex in kidney cells and cell necrosis. The necrosis and consequent cell regeneration are believed to result in kidney tumorigenesis ( Swenberg et al., 1989). Chemicals that have caused kidney tumours in male rats by this mechanism include unleaded gasoline and petroleum hydrocarbons (Short et al., 1987), trichloroethylene, perchloroethylene, and pentachloroethane ( Goldsworthy et al., 1988), decalin, isophore, 1,4-dichlorobenzene, and d-limonene (Swenberg et al., 1989).
Clofibrate causes a decrease in plasma triacylglycerol levels by increasing the activity of lipoprotein lipase, thereby, increasing the removal of VLDL (very low density lipoprotein) from the plasma. Clofibrate can also cause a lowering of plasma cholesterol by inhibiting cholesterol synthesis in the liver and by causing an increase in cholesterol excretion via the bile to the faeces.
Glutathione peroxidase, a selenium-dependent enzyme that is extremely specific for glutathione (GSH), is capable of rapidly detoxifying hydrogen peroxide and certain hydroperoxides.
Also called lipid-lowering agents. They act either by reducing the production of lipoproteins or by increasing their removal from the blood.
A group of metalloenzymes that catalyze a disproportionation reaction in which superoxide is reduced to hydrogen peroxide according to the following equation:
This reactive product can then be removed by the action of catalase or glutathione peroxidase;