Prevention by 2-mercaptoethane Sulfonate and N-acetylcysteine of Renal Oxidative Damage in Rats Treated with Ferric Nitrilotriacetate

Overview

Journal Jpn J Cancer Res

Specialty Oncology

Date 1996 Sep 1

PMID 8878448

Citations 10

Authors

T Umemura

R Hasegawa

A Nishikawa

F Furukawa

S Toyokuni

K Uchida

T Inoue

Y Kurokawa

Affiliations

Soon will be listed here.

Abstract

Ferric nitrilotriacetate (Fe-NTA) is a renal toxicant and carcinogen in rats and mice. We found that its administration results in formation of 4-hydroxy-2-nonenal (HNE) in the renal proximal tubule cells of rats, and 8-hydroxydeoxyguanosine (8-OHdG) adducts in their DNA, suggesting a role for oxidative stress. Since 2-mercaptoethane sulfonate (MESNA) and N-acetylcysteine (NAC), administered orally, have been shown to increase the kidney levels of free thiol groups, their influence on the renal toxicity and carcinogenicity induced by Fe-NTA was examined in the present study. Male Wistar rats were intraperitoneally injected with Fe-NTA (12 mg Fe/kg), and MESNA (100 mg/kg) or NAC (200 mg/kg) was given orally 1 h before and 1 h after this treatment. The animals were killed for tissue analyses 3 h after the Fe-NTA exposure. In accord with our previous reports, HNE-modified protein was detected in the proximal tubules of Fe-NTA-treated rats by means of immunohistochemistry. Likewise, levels of 8-OHdG in the renal nuclear DNA, lipid peroxides as thiobarbituric acid-reactive substances in the kidneys, and blood urea nitrogen and creatinine in the serum were significantly increased by the Fe-NTA treatment. All of these changes were completely inhibited by oral administration of MESNA or NAC. These results suggest that both of these compounds can prevent the oxidative stress induced by Fe-NTA.

Citing Articles

Transferrin receptor 1 upregulation in primary tumor and downregulation in benign kidney is associated with progression and mortality in renal cell carcinoma patients.

Greene C, Attwood K, Sharma N, Gross K, Smith G, Xu B Oncotarget. 2018; 8(63):107052-107075.

PMID: 29291011 PMC: 5739796. DOI: 10.18632/oncotarget.22323.

The Effects of MESNA on the Facial Nerve, an Experimental Animal Study.

Baklaci D, Kum R, Kulacoglu S, Yilmaz Y, Ozcan M J Int Adv Otol. 2017; 14(1):63-67.

PMID: 29092802 PMC: 6354490. DOI: 10.5152/iao.2017.3593.

Vitamin C intake and risk of renal cell carcinoma: a meta-analysis.

Jia L, Jia Q, Shang Y, Dong X, Li L Sci Rep. 2015; 5:17921.

PMID: 26643589 PMC: 4672306. DOI: 10.1038/srep17921.

Chelation in metal intoxication.

Flora S, Pachauri V Int J Environ Res Public Health. 2010; 7(7):2745-88.

PMID: 20717537 PMC: 2922724. DOI: 10.3390/ijerph7072745.

Curcumin attenuates oxidative damage in animals treated with a renal carcinogen, ferric nitrilotriacetate (Fe-NTA): implications for cancer prevention.

Iqbal M, Okazaki Y, Okada S Mol Cell Biochem. 2009; 324(1-2):157-64.

PMID: 19165575 DOI: 10.1007/s11010-008-9994-z.

References

Toyokuni S, Uchida K, Okamoto K, Hiai H, Stadtman E . Formation of 4-hydroxy-2-nonenal-modified proteins in the renal proximal tubules of rats treated with a renal carcinogen, ferric nitrilotriacetate. Proc Natl Acad Sci U S A. 1994; 91(7):2616-20. PMC: 43420. DOI: 10.1073/pnas.91.7.2616. View

Okamoto K, Toyokuni S, Uchida K, Ogawa O, Takenewa J, Kakehi Y . Formation of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins in human renal-cell carcinoma. Int J Cancer. 1994; 58(6):825-9. DOI: 10.1002/ijc.2910580613. View

Umemura T, Sai K, Takagi A, Hasegawa R, Kurokawa Y . Formation of 8-hydroxydeoxyguanosine (8-OH-dG) in rat kidney DNA after intraperitoneal administration of ferric nitrilotriacetate (Fe-NTA). Carcinogenesis. 1990; 11(2):345-7. DOI: 10.1093/carcin/11.2.345. View

Benedetti A, Comporti M, Esterbauer H . Identification of 4-hydroxynonenal as a cytotoxic product originating from the peroxidation of liver microsomal lipids. Biochim Biophys Acta. 1980; 620(2):281-96. DOI: 10.1016/0005-2760(80)90209-x. View

Tsai L, Sokoloski E . The reaction of 4-hydroxy-2-nonenal with N alpha-acetyl-L-histidine. Free Radic Biol Med. 1995; 19(1):39-44. DOI: 10.1016/0891-5849(95)00009-m. View

Izzotti A, Balansky R, Scatolini L, ROVIDA A, DE Flora S . Inhibition by N-acetylcysteine of carcinogen-DNA adducts in the tracheal epithelium of rats exposed to cigarette smoke. Carcinogenesis. 1995; 16(3):669-72. DOI: 10.1093/carcin/16.3.669. View

Okada S, Minamiyama Y, Hamazaki S, Toyokuni S, Sotomatsu A . Glutathione cycle dependency of ferric nitrilotriacetate-induced lipid peroxidation in mouse proximal renal tubules. Arch Biochem Biophys. 1993; 301(1):138-42. DOI: 10.1006/abbi.1993.1125. View

Hamazaki S, Okada S, Toyokuni S, MIDORIKAWA O . Thiobarbituric acid-reactive substance formation of rat kidney brush border membrane vesicles induced by ferric nitrilotriacetate. Arch Biochem Biophys. 1989; 274(2):348-54. DOI: 10.1016/0003-9861(89)90448-7. View

Mihara M, Uchiyama M . Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978; 86(1):271-8. DOI: 10.1016/0003-2697(78)90342-1. View

10.

Wang M, Nishikawa A, Chung F . Differential effects of thiols on DNA modifications via alkylation and Michael addition by alpha-acetoxy-N-nitrosopyrrolidine. Chem Res Toxicol. 1992; 5(4):528-31. DOI: 10.1021/tx00028a011. View

11.

Wood M, Dizdaroglu M, Gajewski E, Essigmann J . Mechanistic studies of ionizing radiation and oxidative mutagenesis: genetic effects of a single 8-hydroxyguanine (7-hydro-8-oxoguanine) residue inserted at a unique site in a viral genome. Biochemistry. 1990; 29(30):7024-32. DOI: 10.1021/bi00482a011. View

12.

Winter C, Segall H, Haddon W . Formation of cyclic adducts of deoxyguanosine with the aldehydes trans-4-hydroxy-2-hexenal and trans-4-hydroxy-2-nonenal in vitro. Cancer Res. 1986; 46(11):5682-6. View

13.

Toyokuni S, Mori T, Dizdaroglu M . DNA base modifications in renal chromatin of Wistar rats treated with a renal carcinogen, ferric nitrilotriacetate. Int J Cancer. 1994; 57(1):123-8. DOI: 10.1002/ijc.2910570122. View

14.

Umemura T, Sai K, Takagi A, Hasegawa R, Kurokawa Y . A possible role for oxidative stress in potassium bromate (KBrO3) carcinogenesis. Carcinogenesis. 1995; 16(3):593-7. DOI: 10.1093/carcin/16.3.593. View

15.

Ormstad K, Ohno Y . N-acetylcysteine and sodium 2-mercaptoethane sulfonate as sources of urinary thiol groups in the rat. Cancer Res. 1984; 44(9):3797-800. View

16.

AWAI M, Narasaki M, Yamanoi Y, Seno S . Induction of diabetes in animals by parenteral administration of ferric nitrilotriacetate. A model of experimental hemochromatosis. Am J Pathol. 1979; 95(3):663-73. PMC: 2042322. View

17.

Cheng K, Cahill D, Kasai H, Nishimura S, Loeb L . 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G----T and A----C substitutions. J Biol Chem. 1992; 267(1):166-72. View

18.

Uchida K, Szweda L, Chae H, Stadtman E . Immunochemical detection of 4-hydroxynonenal protein adducts in oxidized hepatocytes. Proc Natl Acad Sci U S A. 1993; 90(18):8742-6. PMC: 47434. DOI: 10.1073/pnas.90.18.8742. View

19.

Umemura T, Sai K, Takagi A, Hasegawa R, Kurokawa Y . Oxidative DNA damage, lipid peroxidation and nephrotoxicity induced in the rat kidney after ferric nitrilotriacetate administration. Cancer Lett. 1990; 54(1-2):95-100. DOI: 10.1016/0304-3835(90)90097-h. View

20.

Umemura T, Takagi A, Hasegawa R, Kurokawa Y . Oxidative DNA damage and cell proliferation in the livers of B6C3F1 mice exposed to pentachlorophenol in their diet. Fundam Appl Toxicol. 1996; 30(2):285-9. DOI: 10.1006/faat.1996.0066. View