Evidence against a direct role for oxidative stress in cadmium-induced axial malformation in the chick embryo.
Cadmium (Cd) is a powerful inducer of oxidative stress. It also causes ventral body wall defects in chick embryos treated at Hamburger-Hamilton stages 16-17. By measuring malondialdehyde levels (TBARS method) and cotreating with antioxidants (tempol, ascorbate, and N-acetylcysteine), we sought to determine if oxidative stress were directly related to teratogenesis. We also investigated the expression of mRNAs for antioxidant enzymes superoxide dismutase (SOD) -1 and -2, catalase (CAT), and glutathione peroxidase (GPx). RT-PCR showed reductions in SOD-1, SOD-2, and CAT 1 hour after treatment with Cd. MDA levels increased 4 hours after Cd, and remained elevated 24 hours after treatment. Of the antioxidants, only N-acetylcysteine reduced MDA levels to control values. Nonetheless, no antioxidant could reduce embryo lethality or malformation rates. Furthermore, MDA levels 24 hours after treatment were identical in malformed and normal embryos exposed to Cd. Hence, we conclude that oxidative stress may not have a direct role in Cd teratogenesis.
Thompson
Jennifer
J
School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland. jennifer.thompson@ucd.ie
Doi
Takashi
T
Power
Eoin
E
Balasubramanian
Ishwarya
I
Puri
Prem
P
Bannigan
John
J
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D019521:Body Patterning / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D002374:Catalase / Q000096:biosynthesis / Q000235:genetics; D002642:Chick Embryo; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D013723:Teratogens
D000975:Antioxidants; D013723:Teratogens; D002104:Cadmium; D008315:Malondialdehyde; D012313:RNA; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000111:Acetylcysteine