Ferric nitrilotriacetate (Fe-NTA) is a potent hepatic tumor promoter and acts through the generation of oxidative stress.
Fe-NTA is a known renal carcinogen. However, little is known about its carcinogenic potential in liver. In this study we for the first time show that Fe-NTA is a potent hepatic tumor promoter. Fe-NTA administration induced dose dependently the hepatic ornithine decarboxylase (ODC) activity several folds as compared to its activity in the saline-treated rats. Similarly, hepatic DNA synthesis which is measured as [3H]thymidine incorporation in DNA is also increased following Fe-NTA treatment. The effects of Fe-NTA were similar to other tumor promoters not only with respect to inducing ODC activity and [3H]thymidine incorporation in DNA but also in depleting antioxidant armory of the tissue. Fe-NTA depleted levels of glutathione to about 35% of the saline-treated control and activities of antioxidant enzymes catalase, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase decreased significantly (45-55% of saline-treated control). Concomitant with the depletion in antioxidant armory, Fe-NTA augmented hepatic microsomal lipid peroxidation more than three folds. The pretreatment of rats with antioxidants BHA or BHT diminished the observed effects of Fe-NTA. Our data indicate that Fe-NTA is a potent hepatic tumor promoter and acts through a mechanism involving oxidative stress.
Iqbal
M
M
Department of Medical Elementology and Toxicology, Hamdard University, New Delhi, India.
Giri
U
U
Athar
M
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005290:Ferric Compounds / Q000633:toxicity*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D005290:Ferric Compounds; D004247:DNA; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D009955:Ornithine Decarboxylase; D005978:Glutathione; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate