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In vitro curcumin modulates ferric nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H2O2)-induced peroxidation of microsomal membrane lipids and DNA damage.
Teratog Carcinog Mutagen. 2003; Suppl 1:151-60.TC

Abstract

A number of investigations have implicated the involvement of free radicals in various pathogenic process including initiation/promotion stages of carcinogenesis and antioxidants have been considered to be a protective agent for this reason. An iron chelate, ferric nitrilotriacetate (Fe-NTA), is a potent nephrotoxic agent and induces acute and subacute renal proximal tubular necrosis by catalyzing the decomposition of hydrogen peroxide-derived production of hydroxyl radicals, which are known to cause lipid peroxidation and DNA damage. The latter is associated with a high incidence of renal adenocarcinoma in rodents. Lipid peroxidation and DNA damage are the principal manifestation of Fe-NTA-induced toxicity, which could be mitigated by antioxidants. In this study, we therefore investigated the effect of curcumin, a polyphenolic compound from Curcuma longa for a possible protection against lipid peroxidation and DNA damage induced by Fe-NTA and hydrogen peroxide in vitro. Incubation of renal microsomal membrane/and or calf thymus DNA with hydrogen peroxide (40 mM) in the presence of Fe-NTA (0.1 mM) induces renal microsomal lipid peroxidation and DNA damage to about 2.2-and 5.6-fold, respectively, as compared to saline treated control (P<0.001). Induction of renal microsomal lipid peroxidation and DNA damage was modulated by curcumin dose dependently. In lipid peroxidation protection studies, curcumin treatment showed a dose-dependent strong inhibition (18-80% inhibition, P<0.05-0.001) of Fe-NTA and hydrogen peroxide-induced lipid peroxidation as measured by MDA formation in renal microsomes. Similarly, in DNA-sugar damage protection studies, curcumin treatment also showed a dose dependent inhibition (22-57% inhibition, P<0.05-0.001) of DNA-sugar damage. From these studies, it was concluded that curcumin modulates Fe-NTA and hydrogen peroxide-induced peroxidation of microsomal membrane lipids and DNA damage. Curcumin might, therefore, be a suitable candidate for the chemoprevention of Fe-NTA-associated cancer.

Authors+Show Affiliations

Department of Pathological Research, Faculty of Medicine, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. m_iqbal2k@hotmail.comNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12616605

Citation

Iqbal, Mohammad, et al. "In Vitro Curcumin Modulates Ferric Nitrilotriacetate (Fe-NTA) and Hydrogen Peroxide (H2O2)-induced Peroxidation of Microsomal Membrane Lipids and DNA Damage." Teratogenesis, Carcinogenesis, and Mutagenesis, vol. Suppl 1, 2003, pp. 151-60.
Iqbal M, Okazaki Y, Okada S. In vitro curcumin modulates ferric nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H2O2)-induced peroxidation of microsomal membrane lipids and DNA damage. Teratog Carcinog Mutagen. 2003;Suppl 1:151-60.
Iqbal, M., Okazaki, Y., & Okada, S. (2003). In vitro curcumin modulates ferric nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H2O2)-induced peroxidation of microsomal membrane lipids and DNA damage. Teratogenesis, Carcinogenesis, and Mutagenesis, Suppl 1, 151-60.
Iqbal M, Okazaki Y, Okada S. In Vitro Curcumin Modulates Ferric Nitrilotriacetate (Fe-NTA) and Hydrogen Peroxide (H2O2)-induced Peroxidation of Microsomal Membrane Lipids and DNA Damage. Teratog Carcinog Mutagen. 2003;Suppl 1:151-60. PubMed PMID: 12616605.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro curcumin modulates ferric nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H2O2)-induced peroxidation of microsomal membrane lipids and DNA damage. AU - Iqbal,Mohammad, AU - Okazaki,Yasumasa, AU - Okada,Shigeru, PY - 2003/3/5/pubmed PY - 2003/9/17/medline PY - 2003/3/5/entrez SP - 151 EP - 60 JF - Teratogenesis, carcinogenesis, and mutagenesis JO - Teratog Carcinog Mutagen VL - Suppl 1 N2 - A number of investigations have implicated the involvement of free radicals in various pathogenic process including initiation/promotion stages of carcinogenesis and antioxidants have been considered to be a protective agent for this reason. An iron chelate, ferric nitrilotriacetate (Fe-NTA), is a potent nephrotoxic agent and induces acute and subacute renal proximal tubular necrosis by catalyzing the decomposition of hydrogen peroxide-derived production of hydroxyl radicals, which are known to cause lipid peroxidation and DNA damage. The latter is associated with a high incidence of renal adenocarcinoma in rodents. Lipid peroxidation and DNA damage are the principal manifestation of Fe-NTA-induced toxicity, which could be mitigated by antioxidants. In this study, we therefore investigated the effect of curcumin, a polyphenolic compound from Curcuma longa for a possible protection against lipid peroxidation and DNA damage induced by Fe-NTA and hydrogen peroxide in vitro. Incubation of renal microsomal membrane/and or calf thymus DNA with hydrogen peroxide (40 mM) in the presence of Fe-NTA (0.1 mM) induces renal microsomal lipid peroxidation and DNA damage to about 2.2-and 5.6-fold, respectively, as compared to saline treated control (P<0.001). Induction of renal microsomal lipid peroxidation and DNA damage was modulated by curcumin dose dependently. In lipid peroxidation protection studies, curcumin treatment showed a dose-dependent strong inhibition (18-80% inhibition, P<0.05-0.001) of Fe-NTA and hydrogen peroxide-induced lipid peroxidation as measured by MDA formation in renal microsomes. Similarly, in DNA-sugar damage protection studies, curcumin treatment also showed a dose dependent inhibition (22-57% inhibition, P<0.05-0.001) of DNA-sugar damage. From these studies, it was concluded that curcumin modulates Fe-NTA and hydrogen peroxide-induced peroxidation of microsomal membrane lipids and DNA damage. Curcumin might, therefore, be a suitable candidate for the chemoprevention of Fe-NTA-associated cancer. SN - 0270-3211 UR - https://www.unboundmedicine.com/medline/citation/12616605/In_vitro_curcumin_modulates_ferric_nitrilotriacetate__Fe_NTA__and_hydrogen_peroxide__H2O2__induced_peroxidation_of_microsomal_membrane_lipids_and_DNA_damage_ L2 - https://doi.org/10.1002/tcm.10070 DB - PRIME DP - Unbound Medicine ER -