Role of gamma-glutamyltranspeptidase and beta-lyase in the nephrotoxicity of hexachloro-1,3-butadiene and methyl mercury in mice. 1990

J de Ceaurriz, and M Ban
Institut National de Recherche et de Sécurité, Vandoeuvre, France.

Male Swiss OF1 mice received a single oral dose of either 80 mg/kg hexachloro-1,3-butadiene (HCBD) or 80 mg/kg methyl mercury (MeHg). Examination of cryostat kidney sections stained for alkaline phosphatase (APP) revealed damage to about 50% of the proximal tubules after 8 h. Pretreatment with the gamma-glutamyltranspeptidase (gamma-GT) inactivator AT-125 (Acivin, 50 mg/kg i.p., plus 50 mg/kg p.o., reduced the number of damaged tubules by 59 and 58% in mice treated with HCBD and MeHg, respectively. Pretreatment with the two beta-lyase inhibitors, amino-oxyacetic acid (AOAA, 3 x 100 mg/kg p.o.) and DL-propargylglycine (PPG, 300 mg/kg i.p. plus 300 mg/kg p.o.), reduced HCBD nephrotoxicity by 46 and 59%, respectively, but did not protect against MeHg nephrotoxicity. The results support a role for gamma-GT and beta-lyase in the mouse renal toxicity of HCBD and implicate gamma-GT but not beta-lyase in MeHg-induced nephrotoxicity in mice.

UI MeSH Term Description Entries
D007555 Isoxazoles Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions. Isoxazole
D007683 Kidney Tubular Necrosis, Acute Acute kidney failure resulting from destruction of EPITHELIAL CELLS of the KIDNEY TUBULES. It is commonly attributed to exposure to toxic agents or renal ISCHEMIA following severe TRAUMA. Lower Nephron Nephrosis,Acute Kidney Tubular Necrosis,Lower Nephron Nephroses,Nephron Nephroses, Lower,Nephron Nephrosis, Lower,Nephroses, Lower Nephron,Nephrosis, Lower Nephron
D007687 Kidney Tubules, Proximal The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE. Proximal Kidney Tubule,Proximal Renal Tubule,Kidney Tubule, Proximal,Proximal Kidney Tubules,Proximal Renal Tubules,Renal Tubule, Proximal,Renal Tubules, Proximal,Tubule, Proximal Kidney,Tubule, Proximal Renal,Tubules, Proximal Kidney,Tubules, Proximal Renal
D008190 Lyases A class of enzymes that catalyze the cleavage of C-C, C-O, and C-N, and other bonds by other means than by hydrolysis or oxidation. (Enzyme Nomenclature, 1992) EC 4. Desmolase,Desmolases,Lyase
D008767 Methylmercury Compounds Organic compounds in which mercury is attached to a methyl group. Methyl Mercury Compounds,Compounds, Methyl Mercury,Compounds, Methylmercury,Mercury Compounds, Methyl
D010293 Pargyline A monoamine oxidase inhibitor with antihypertensive properties. Pargyline Hydrochloride,Hydrochloride, Pargyline
D002070 Butadienes Four carbon unsaturated hydrocarbons containing two double bonds. Butadiene Derivative,Butadiene Derivatives,Derivative, Butadiene,Derivatives, Butadiene
D005723 gamma-Glutamyltransferase An enzyme, sometimes called GGT, with a key role in the synthesis and degradation of GLUTATHIONE; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid. GGTP,Glutamyl Transpeptidase,gammaglutamyltransferase,gamma-Glutamyl Transpeptidase,Transpeptidase, Glutamyl,Transpeptidase, gamma-Glutamyl,gamma Glutamyl Transpeptidase,gamma Glutamyltransferase
D005998 Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Aminoacetic Acid,Glycine, Monopotassium Salt,Glycine Carbonate (1:1), Monosodium Salt,Glycine Carbonate (2:1), Monolithium Salt,Glycine Carbonate (2:1), Monopotassium Salt,Glycine Carbonate (2:1), Monosodium Salt,Glycine Hydrochloride,Glycine Hydrochloride (2:1),Glycine Phosphate,Glycine Phosphate (1:1),Glycine Sulfate (3:1),Glycine, Calcium Salt,Glycine, Calcium Salt (2:1),Glycine, Cobalt Salt,Glycine, Copper Salt,Glycine, Monoammonium Salt,Glycine, Monosodium Salt,Glycine, Sodium Hydrogen Carbonate,Acid, Aminoacetic,Calcium Salt Glycine,Cobalt Salt Glycine,Copper Salt Glycine,Hydrochloride, Glycine,Monoammonium Salt Glycine,Monopotassium Salt Glycine,Monosodium Salt Glycine,Phosphate, Glycine,Salt Glycine, Monoammonium,Salt Glycine, Monopotassium,Salt Glycine, Monosodium
D000469 Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.

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