Search

The administration of Protein A, a cell wall protein of Staphylococcus aureus Cowan I cells, causes an induction of glutathione-s-transferase in rat liver. Proteins, cross reactive with anti human glutathione-s-transferase, acidic (π), basic (α) and neutral (μ) isoenzymes, are induced by 5.8, 2.2 and 6.15 fold respectively. The induction of glutathione -s-transferases, at least in part, might play a role in manifestation of therapeutic properties of Protein A.

Administration of benzene (i.p. 1.0 mL/kg body weight) for 3 consecutive days produced leucopenia and lymphocytopenia in female albino rats. In addition, the total iron content, lipid peroxidation and superoxide dismutase activity of the liver and bone marrow were significantly (P0.001) increased. Low molecular weight (LMW) bleomycin-detectable iron accumulated only in bone marrow. Prior administration of Protein A (PA), a multipotent immunostimulant and interferon inducer (60 micrograms/kg body weight, i.v. twice weekly for 2 weeks), ameliorated most of the adverse effects of benzene. PA restored the changes in hepatic histological architecture, reversed leucopenia and superoxide dismutase activity, lipid peroxidation, total iron content and LMW iron content of bone marrow were normalized. Isozymes of glutathione-S-transferase (alpha, pi, mu) which decreased following benzene exposure increased in PA pretreated benzene exposed rats. This study suggests that pretreatment with PA modulates the toxicity of benzene.

Administration of nickel (50 μ moles Ni/kg as NiCl2•6H2O, subcutaneously) to partially hepatectomized rats at 8, 16, 24 and 72 hrs revealed that it did not produce any change in the levels of hepatic or renal glutathione at any time interval when compared with saline treated hepatectomized rats. Remarkable changes were however observed in glutathione-S-transferase and phosphoglucomutase at 16 and 24 hrs in liver while only at 8 hrs in kidney. The effect of various doses of nickel (50, 100 and 150 μ mole Ni/kg) at 16 hrs revealed that 100 μ moles nickel produced maximum enhancement in the levels of all these parameters in liver while in kidney practically no change was observed.

The chelating drugs namely ethylenediamine tetraacetic acid (EDTA), 1,2,cyclohexylenediamine tetraacetic acid (CDTA), hydroxyethylenediamine triacetic acid (HEDTA) diethylenetriamine pentaacetic acid (DTPA), and triethylenetetraamine hexaacetic acid (TTHA), were examined for the mobilization of nickel from body organs of sham operated and partially hepatectomized rats in early nickel poisoning. These chelating drugs successfully reduced the body burden of nickel from both the nickel treated experimental groups. EDTA was relatively more effective in reducing the hepatic content of nickel while CDTA and HEDTA were more effective in reducing its renal content. These drugs also reduced nickel burden in heart and lung to variable degrees. The over all efficacy of the chelating drugs are in the order: EDTA > CDTA > HEDTA > TTHA > DTPA

The effect of gamma-hexachlorocyclohexane (HCH), (25 mg/kg body weight, i.p., administered for 4 consecutive days) on the induction of types of cytochrome P-450 in rat liver microsomes was studied. Induced proteins were characterized by "Western" blot analysis, using anticytochrome P-450 antibodies. It was observed that HCH is a "mixed-type" inducer and mediates induction of cytochrome P-450 b/e forms by several fold and of cytochrome P-450 c and d forms by nearly three fold.

The LD50 of the following metal-binding chelating drugs, EDTA, diethylenetriaminepentaacetic acid (DTPA), hydroxyethylenediaminetriacetic acid (HEDTA), cyclohexanediaminotetraacetic acid (CDTA) and triethylenetetraminehexaacetic acid (TTHA) was evaluated in terms of mortality in rats after intraperitoneal administration and was found to be in the order: CDTA greater than EDTA greater than DTPA greater than TTHA greater than HEDTA. A possible correlation between the toxicity and molecular structure of the compounds is discussed.