Molecular inhibitory mechanisms of antioxidant enzymes in rat liver and kidney by cadmium.
Catalase, Mn-superoxide dismutase (MnSOD) and Cu,Zn-superoxide dismutase (CuZnSOD) activities were studied in rat liver and kidney 6-48 h after CdCl(2) intraperitoneal administration or 10-30 days daily oral CdCl(2) intake in drinking water. This approach provided some indications as to the sensitivity of each enzyme to cadmium toxicity. These experiments showed that the formation of thiobarbituric acid reactive substance (TBARS) did not strictly depend on how well the antioxidant enzyme worked. From in vitro experiments it appeared that TBARS removal by vitamin E did not restore the three enzyme activities at all. As for cadmium's inhibitory mechanism on catalase activity, our data, obtained in the pH range 6.0-8.0, are a preliminary indication that the negative effect of this metal is probably due to imidazole residue binding of His-74 which is essential in the decomposition of hydrogen peroxide. Cadmium inhibition of liver mitochondrial MnSOD activity was completely removed by Mn(2+) ions, suggesting that the reducing effect on this enzyme is probably due to the substitution of cadmium for manganese. We also observed the antioxidant capacity of Mn(2+) ions, since they were able to normalize the increased TBARS levels occurring when liver mitochondria were exposed to cadmium. The reduced activity of CuZnSOD does not seem to be due to the replacement of Zn by Cd, nor to the peroxides formed. As this enzyme activity was almost completely recovered after 48 h, we hypothesize that the momentary inhibition is imputable to a cadmium/enzyme interaction. This causes some perturbation in the enzyme topography which is critical for its catalytic activity. The pathological implications linked to antioxidant enzyme disorders induced by cadmium toxicity are discussed.
Department of Pharmaco-Biology, Laboratory of Veterinary Biochemistry, University of Bari, Str. Prov. per Casamassima, Km 3, 70010 Valenzano, Bari, Italy.
Elisabetta
E
Casalino
Giovanna
G
Calzaretti
Cesare
C
Sblano
Clemente
C
Landriscina
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002104:Cadmium / Q000008:administration & dosage / Q000633:toxicity*; D002105:Cadmium Poisoning / Q000201:enzymology*; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D011506:Proteins; D017392:Thiobarbituric Acid Reactive Substances; D002104:Cadmium; D014810:Vitamin E; D002374:Catalase; D013482:Superoxide Dismutase; D008274:Magnesium