Ascorbic acid (AA) is a naturally occurring phenolic compound with antioxidant properties used in food, cosmetics, and pharmaceutical products. In this study, the effect of AA on ferric nitrilotriacetate (Fe-NTA)-induced hepatotoxicity in rats has been examined. Fe-NTA alone enhances ornithine decarboxylase activity to 4.5-fold and tritiated thymidine incorporation in DNA to 3.6-fold in livers compared with the corresponding saline-treated controls. The enhanced ornithine decarboxylase activity and DNA synthesis showed a reduction to 3.02- and 1.88-fold, respectively, at a higher dose of 2 mg AA per day per animal, compared with the Fe-NTA-treated groups. Fe-NTA treatment also enhanced the hepatic microsomal lipid peroxidation to 1.7-fold compared to saline-treated controls. These changes were reversed significantly in animals receiving pretreatment of AA. The present data shows that AA can reciprocate the toxic effects of Fe-NTA and can serve as a potent chemopreventive agent to suppress oxidant-induced tissue injury and hepatotoxicity in rats.
AtharMIqbalM (1998) Ferric-nitrilotriacetate promotes N-diethylnitrosamine induced renal tumerigenesis in the rat: implications for the involvement of oxidative stress. Carcinogenisis19(6): 1133–1139.
2.
AwaiMNarasakiMYamanoiYSenoS (1979) Induction of diabetes in animals by parentral administration of ferric nitrilotriacetate. A model of experimental hemochromatosis. American Journal of Pathology (95): 663–672.
3.
BahnemannRLeiboldEKittelBJellertWJackhR (1998) Different patterns of kidney toxicity after subacute administration of Na-nitrilotriacetate acid and Fe-nitrilotriacetic acid to Wistar rats. Toxicological Sciences46(1): 166–175.
4.
BartschHFrankN (1996) Blocking the endogenous formation of N-nitroso compounds and related carcinogenesis. IARC Scientific Publications139: 189–201.
5.
BuiattiEMunozN (1996) Chemoprevention of stomach cancer. IARC Scientific Publications136: 35–39.
6.
DrakeIMDavisMJMapstoneNPDixonMFSchorahCJWhiteKL. (1996) Ascorbic acid may protect against human gastric cancer by scavenging mucosal oxygen. Carcinogenesis17(3): 559–562.
7.
IqbalMGiriUAtharM (1995) Ferric nitrilotriacetate (Fe-NTA) is a potent hepatic tumor promoter and acts through the generation of oxidative stress. Biochemical and Biophysical Research Communications2212: 557–563.
8.
IqbalMGiriUGiriDKAlamMSAtharM (1999) Age-dependent renal accumulation of 4-hydroxy-2-nonrenal (HNE)-modified proteins following parenteral administration of ferric nitrilotriacetate commensurate with its differential toxicity: implications for the involvement of HNE-protien adducts in oxidative stress and carcinogenesis. Archives of Biochemistry and Biophysics365(1): 101–112.
9.
IqbalMSharmaSDRezazadehHHasanNAbdullahMAtharM (1996) Glutathione metabolizing enzymes and oxidative stress in ferric nitrilotriacetate (Fe-NTA) mediated hepatic injury. Redox Report2(6): 385–391.
10.
LevineMRumseySCDaruwalaRParkJBWangY (1999) Critieria and recommendation for vitamin C intake. Journal of the American Medical Association281(15): 1415–1423.
11.
NandiDPatraRCSwarupD (2005) Effect of cysteine, methionine, ascorbic acid and thiamine on arsenic-induced oxidative stress and biochemical alterations in rats. Toxicology211
(1–2): 26–35.
12.
NomotoMYamaguchiRKawamuraMKohnoKKasaiH (1999) Analysis of 8-hydroxyguanine in rat kidney genomic DNA after administration of a renal carcinogen, ferric nitrilotriactetateCarcinogenesis20(5): 837–841.
PatraRCSwarupDDwivediSK (2001) Antioxidant effects of α tocopherol, ascorbic acid and l-methionine on lead induced oxidative stress to the liver, kidney and brain in rats. Toxicology162(2): 81–88.
15.
PatelRKTrivediAHRoySKBhatavdekarJMShahPMPatelDD (1998) Influence of alpha-tocopherol and ascorbic acid on pan-masala induced genomic damage. An in vitro experiment. Journal of Experimental and Clinical Cancer Research17(4): 419–424.
16.
ToyokuniSMoriTDizdarogluM (1994a) DNA base modifications in renal chromatin of Wistar rats treated with renal carcinogen, ferric-nitrilotriactate. International Journal of Cancer57: 123–128.
17.
ToyokuniSOkadaKKondoSNishiokaHTanakaTNishiyamaY. (1998) Development of high-grade renal cell carcinomas in rats independently of somatic mutations in the Tsc2 and VHL tumor suppressor genes. Japanese Journal of Cancer Research89(8): 814–820.
18.
ToyokuniSUchidaKOkamatoKNakakukiYHHiaiHStadtmanER (1994b) Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules of rats treated with renal carcinogen, ferric nitrilotriacetate. Proceedings of the National Academy of Sciences United States of the America91: 2616–2620.
19.
TsouTCChenCLLiuTYYangJL (1996) Induction of 8-hydroxyguanosine in DNA by chromium (III) plus hydrogen peroxide and its prevention by scavengers. Carcinogenesis17(1): 103–108.
20.
Van-PoppelGVan den BergH (1997) Vitamins and cancer. Cancer Letters114(1–2): 195–202.
21.
YamadaMAwaiMOkigakiT (1990) Rapid in vitro transformation system for liver epithelial cells by iron chelate, Fe-NTA. Cytotechnology3: 146–156.
22.
ZhangSHunterDJFormanMRRosnerBASpeizerFEColditzGA. (1999) Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. Journal of the National Cancer Institute91(6): 547–556.
