In vitro curcumin modulates ferric nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H2O2)-induced peroxidation of microsomal membrane lipids and DNA damage.
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.
Iqbal
Mohammad
M
Department of Pathological Research, Faculty of Medicine, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan. m_iqbal2k@hotmail.com
Okazaki
Yasumasa
Y
Okada
Shigeru
S
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D006861:Hydrogen Peroxide / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D007668:Kidney / Q000737:chemistry / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D008861:Microsomes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D009571:Nitrilotriacetic Acid / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*
D016588:Anticarcinogenic Agents; D005290:Ferric Compounds; D008563:Membrane Lipids; D004247:DNA; C427203:calf thymus DNA; D006861:Hydrogen Peroxide; D003474:Curcumin; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate