Skip to main content
Log in

Relationship between body iron stores and diquat toxicity in male Fischer-344 rats

  • Published:
Biometals Aims and scope Submit manuscript

Abstract

The effects of body iron stores on diquat (DQ)-induced toxicity were examined in male Fischer-344 rats, which are sensitive to this herbicide. The rats (5 weeks old) were fed diets containing 40 (lower iron storage [LIS] group) or 320 ppm iron (higher iron storage [HIS] group) for 5 weeks. The concentrations of nonheme iron and ferritin in the liver and kidney were significantly higher in the HIS group than in the LIS group (P<0.0001), although there was no significant differences between the HIS and LIS groups in hematological parameters, including red blood cell count, hemoglobin concentration, and mean corpuscular volume. Three hours after administration of 0.1 mmol DQ/kg, serum alanine aminotransferase and urea nitrogen were significantly higher than in controls (saline injection) for both the LIS and HIS groups (P<0.01), and, after DQ injection, these parameters were significantly higher in the HIS group than in the LIS group (P<0.01). When the rats were injected with 0.075 or 0.1 mmol DQ/kg, the survival time was significantly shorter in the HIS group than in the LIS group (P<0.05). These findings suggest that higher body iron stores result in more severe DQ toxicity in Fischer-344 rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • American Institute of Nutrition (1977). Report of the American Institute of Nutrition ad hoc committee on standards for nutritional studies. J Nutr 107:1340–1348

    Google Scholar 

  • Bomford A, Conlon-Hollingshead C, Munro HN (1981) Adaptive responses of rat tissue isoferritins to iron administration. Changes in subunit synthesis, isoferritin abundance, and capacity for iron storage. J Biol Chem 256:948–955

    PubMed  CAS  Google Scholar 

  • Clothier B, Robinson S, Akhtar RA, et al (2000) Genetic variation of basal iron status, ferritin and iron regulatory protein in mice: potential for modulation of oxidative stress. Biochem Pharmacol 59:115–122

    Article  PubMed  CAS  Google Scholar 

  • Crichton RR (1990) Proteins of iron storage and transport. Adv Prot Chem 40:281–363

    Article  CAS  Google Scholar 

  • Ganne-Carrié N, Christidis C, Chastang C, et al (2000) Liver iron is predictive of death in alcoholic cirrhosis: a multivariate study of 229 consecutive patients with alcoholic and/or hepatitis C virus cirrhosis: a prospective follow up study. Gut 46:277–282

    Article  PubMed  Google Scholar 

  • Gupta S, Husser RC, Geske RS, Welty SE, Smith CV (2000) Sex differences in diquat-induced hepatic necrosis and DNA fragmentation in Fischer 344 rats. Toxicol Sci 54:203–211

    Article  PubMed  CAS  Google Scholar 

  • Gupta S, Rogers LK, Smith CV (1994) Biliary excretion of lysosomal enzymes, iron, and oxidized protein in Fischer-344 and Sprague–Dawley rats and the effects of diquat and acetaminophen. Toxicol Appl Pharmacol 125:42–50

    Article  PubMed  CAS  Google Scholar 

  • Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, Hu FB (2004) Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA 291:711–717

    Article  PubMed  CAS  Google Scholar 

  • Jones GM, Vale JA (2000) Mechanisms of toxicity, clinical features, and management of diquat poisoning: a review. Clin Toxicol 38:123–128

    Article  CAS  Google Scholar 

  • Kato J, Kobune M, Kohgo Y, et al (1996) Hepatic iron deprivation prevents spontaneous development of fulminant hepatitis and liver cancer in Long-Evans Cinnamon rats. J Clin Invest 98:923–929

    Article  PubMed  CAS  Google Scholar 

  • Lee TS, Shiao MS, Pan CC, Chau LY (1999) Iron-deficient diet reduces atherosclerotic lesions in apoE-deficient mice. Circulation 99:1222–1229

    PubMed  CAS  Google Scholar 

  • Linder MC, Moor JR, Scott LE, Munro HN (1973) Mechanism of sex difference in rat tissue iron stores. Biochim Biophys Acta 297:70–80

    PubMed  CAS  Google Scholar 

  • McCord JM (1996) Effects of positive iron status at a cellular level. Nutr Rev 54:85–88

    Article  PubMed  CAS  Google Scholar 

  • Merk K, Mattson B, Mattson A, Holm G, Gullbring B, Björkholm M (1990) The incidence of cancer among blood donors. Int J Epidemiol 19:505–509

    PubMed  CAS  Google Scholar 

  • Petry TW, Wolfgang GHI, Jolly RA, Ochoa R, Donarski WJ (1992) Antioxidant-dependent inhibition of diquat-induced toxicity in vivo. Toxicology 74:33–43

    Article  PubMed  CAS  Google Scholar 

  • Reif DW (1992) Ferritin as a source of iron for oxidative damage. Free Rad Biol Med 12:417–427

    Article  PubMed  CAS  Google Scholar 

  • Reif DW, Beales ILP, Thomas CE, Aust SD (1988) Effect of diquat on the distribution of iron in rat liver. Toxicol Appl Pharmacol 93:506–510

    Article  PubMed  CAS  Google Scholar 

  • Rikans LE, Ardinska V, Hornbrook KR (1997) Age-associated increase in ferritin content of male rat liver: Implication for diquat-mediated oxidative injury. Arch Biochem Biophys 344:85–93

    Article  PubMed  CAS  Google Scholar 

  • Rikans LE, Cai Y (1992) Age-associated enhancement of diquat-induced lipid peroxidation and cytotoxicity in isolated rat hepatocytes. J Pharmacol Exp Ther 262:271–278

    PubMed  CAS  Google Scholar 

  • Rikans LE, Cai Y (1993) Diquat-induced oxidative damage in BCNU-pretreated hepatocytes of mature and old rats. Toxicol Appl Pharmacol 118:263–270

    Article  PubMed  CAS  Google Scholar 

  • Rikans LE, Moore DR, Snowden CD (1991) Sex-dependent differences in the effects of aging on antioxidant defense mechanisms of rat liver. Biochim Biophys Acta 1074:195–200

    PubMed  CAS  Google Scholar 

  • Smith CV (1987) Evidence for participation of lipid peroxidation and iron in diquat-induced hepatic necrosis in vivo. Mol Pharmacol 32:417–422

    PubMed  CAS  Google Scholar 

  • Smith CV, Hughes H, Lauterburg BH, Mitchell JR (1985) Oxidant stress and hepatic necrosis in rats treated with diquat. J Pharmacol Exp Ther 235:172–177

    PubMed  CAS  Google Scholar 

  • Stevens RG, Graubard BI, Micozzi MS, Neriishi K, Blumberg BS (1994) Moderate elevation of body iron level and increased risk of cancer occurrence and death. Int J Cancer 56:364–369

    PubMed  CAS  Google Scholar 

  • Stookey LL (1970) Ferrozine-a new spectrophotometric reagent for iron. Anal Chem 42:779–781

    Article  CAS  Google Scholar 

  • Thomas CE, Aust SD (1986) Reductive release of iron from ferritin by cation free radicals of paraquat and other bipyridyls. J Biol Chem 261:13064–13070

    PubMed  CAS  Google Scholar 

  • Watanabe K, Hayashi K, Miyamoto T, Tanaka M, Okano S, Yamamoto S (2000) Characterization of ferritin and ferritin-binding proteins in canine serum. BioMetals 13:57–63

    Article  PubMed  CAS  Google Scholar 

  • Zuyderhoudt FMJ, Jörning GGA, De Haan JG, Samson G, Van Gool J (1980) Rat liver storage iron and plasma ferritin during d-galactosamine-HCl-induced hepatitis. Clin Sci 58:321–325

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kiyotaka Watanabe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abe, T., Kinda, T., Takano, Y. et al. Relationship between body iron stores and diquat toxicity in male Fischer-344 rats. Biometals 19, 651–657 (2006). https://doi.org/10.1007/s10534-006-9002-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10534-006-9002-6

Key words

Navigation