GST isoenzymes in matched normal and neoplastic breast tissue.

The potential to metabolize endogenous and exogenous substances may influence breast cancer development and tumor growth. Therefore we investigated GST activity and the protein expression of glutathione S-transferases (GSTs) isoenzymes known to be involved in the metabolism of endogenous and exogenous carcinogens in breast cancer tissue to obtain new information on their possible role in tumor progression. The interindividual variation in the conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) and of 1,2-epoxy-3-(p-nitrophenoxy) propane (EPNP) with glutathione (GSH) by cytosolic glutathione S-transferases (GSTs) were investigated in human breast matched normal and tumor samples. The GSTA, GSTM, GSTP and GSTT isoenzymes from the crude extracts of matched breast normal and tumor tissues in terms of their immunological properties using western blotting were compared. In most of the samples, the GST activities were higher in the tumor than in the normal cytosolic fractions against both CDNB and EPNP. In the western blotting analysis, it was proved statistically that in normal and tumor epithelial cells, there was difference between GST pi and theta isoenzymes expressions (p0.05). In normal epithelium there was a stronger GST theta expression than in invasive tumor tissues (p=0.013). However, the stronger GST pi expression was observed in tumor epithelium than in normal epithelium in human breast cancers (p=0.000). We found the GSTP protein level and GST activities were higher in the breast tumor than in the normal cytosolic fractions against both CDNB and EPNP, thus implicating a certain biological importance.

Effect of bis(acetato)tetrakis(imidazole) copper(II) in delaying the onset and reducing the mortality rate of strychnine- and thiosemicarbazide- induced convulsions.

The anticonvulsant activity of bis(acetato)tetrakis(imidazole) copper(II), Cu(OAc)2(Im)4, was studied in normal mice using chemical convulsions induced by strychnine, thiosemicarbazide, picrotoxin, and pentelenetetrazol. Intraperitoneal administration of Cu(OAc)2(Im)4, 50 mg/kg body mass, has delayed the onset of strychnine (3 mg/kg)-induced convulsion by 204% (p < or = 0.005) and thiosemicarbazide (20 mg/kg)-induced convulsant by 61% (p < or = 0.005). The changes in the onset of picrotoxin- (6 mg/kg) and pentelenetetrazol (50 mg/kg)-induced convulsions were not significant. The same dosage of the copper compound was effective in delaying the lethal time and reducing the mortality rate of treated animals. The anticonvulsant activity of Cu(OAc)2(Im)4 complex against strychnine was not related to its constituents because the inorganic form of copper such as copper chloride, copper acetate, and the parent imidazole has no anticonvulsant activity. Other copper(II) complexes like copper(II)aspirinate and bis(acetato)bis(2-methyl imidazole) copper(II) were less effective.

Hypoglycemic effect of copper(II) acetate imidazole complexes.

The effect of copper(II) complexes on glucose metabolism was studied in normal and streptozotocin-induced diabetic rats. The copper(II) complexes used were bis(acetato)tetrakis(imidazole) copper (II), [Cu(OAc)2(Im)4], bis(acetato)bis(2-methylimidazole) copper(II), [Cu(OAc)2(2mIm)2], bis(acetato)bis(1,2-dimethylimidazole) copper(II), [Cu(OAc)2(1,2dmIm)2], and bis(acetato)bis(mu-acetato)tetrakis(N-methylimidazole) copper(II) hexaaquo, [Cu2(OAc)4-(NmIm)4].6H2O. Intramuscular administration of various doses of Cu(OAc)2(Im)4 ranging from 10 to 100 mg/kg body mass to overnight fasted rats decreased blood glucose levels in a dose-dependent manner. Maximum hypoglycemic effect was observed 3 h after administration and lasted for at least 6 h. Treatment with 100 mg/kg body mass of Cu(OAc)2(Im)4 caused hypoglycemic shock, which was irreversible and even lethal. Blood insulin levels were reduced sharply during this hypoglycemic shock. Similar changes in blood glucose level were achieved using Cu(OAc)2(2mIm)2. The same pattern of hypoglycemia, although less pronounced, was observed for Cu2(OAc)4(NmIm)4.6H2O and Cu(OAc)2(1,2dmIm)2. Binary copper(II) acetate complex, the ligand imidazole, and the inorganic form of copper, such as copper(II) chloride, had no significant effect on blood glucose level. These results indicate that the hypoglycemic activity of these complexes varies with the imidazole ligand and structure of the complex.