Hydrogen peroxide-induced cell and tissue injury: protective effects of Mn2+.
Recent evidence indicates that under in vitro conditions, superoxide anion and hydrogen peroxide (H2O2) are unstable in the presence of manganese ion (Mn2+). The current studies show that in the presence of Mn2+, H2O2-mediated injury of endothelial cells is greatly attenuated. A source of bicarbonate ion and amino acid is required for Mn2+ to exert its protective effects. Injury by phorbol ester-activated neutrophils is also attenuated under the same conditions. EDTA reverses the protective effects. Acute lung injury produced in vivo in rats by intratracheal instillation of glucose-glucose oxidase is almost completely blocked in rats treated with Mn2+ and glycine. Conversely, treatment of rats with EDTA, a chelator of Mn2+, markedly accentuates lung injury caused by glucose-glucose oxidase. These data are consistent with the findings of others that Mn2+ can facilitate direct oxidation of amino acids with concomitant H2O2 disproportionation. This could form the basis of a new therapeutic approach against oxygen radical-mediated tissue injury.
Varani
J
J
Department of Pathology, University of Michigan, Ann Arbor.
Ginsburg
I
I
Gibbs
D F
DF
Mukhopadhyay
P S
PS
Sulavik
C
C
Johnson
K J
KJ
Weinberg
J M
JM
Ryan
U S
US
Ward
P A
PA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001639:Bicarbonates / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004492:Edetic Acid / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology; D005609:Free Radicals; D005947:Glucose / Q000633:toxicity; D005949:Glucose Oxidase / Q000633:toxicity; D005998:Glycine / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008345:Manganese / Q000494:pharmacology* / Q000627:therapeutic use; D009504:Neutrophils / Q000276:immunology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology; D051381:Rats; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D001639:Bicarbonates; D005609:Free Radicals; D013481:Superoxides; D008345:Manganese; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D005947:Glucose; D010100:Oxygen; D005998:Glycine