Emerging syntheses and findings of new metallic nanoparticles (MNPs) have become an important aspect in various fields including diagnostic imaging. To date, iodine has been utilized as a radiographic contrast medium. However, the raise concern of iodine threats on iodine-intolerance patient has led to search of new contrast media with lower toxic level. In this animal modeling study, 14 nm iron oxide nanoparticles (IONPs) with silane-polyethylene glycol (SiPEG) and perchloric acid have been assessed for toxicity level as compared to conventional iodine. The nanotoxicity of IONPs was evaluated in liver biochemistry, reactive oxygen species production (ROS), lipid peroxidation mechanism, and ultrastructural evaluation using transmission electron microscope (TEM). The hematological analysis and liver function test (LFT) revealed that most of the liver enzymes were significantly higher in iodine-administered group as compared to those in normal and IONPs groups (P < 0.05). ROS production assay and lipid peroxidation indicator, malondialdehyde (MDA), also showed significant reductions in comparison with iodine group (P < 0.05). TEM evaluation yielded the aberration of nucleus structure of iodine-administered group as compared to those in control and IONPs groups. This study has demonstrated the less toxic properties of IONPs and it may postulate that IONPs are safe to be applied as radiographic contrast medium.
This study was aimed to evaluate the effect of Strobilanthes crispus extract for possible protection against lipid peroxidation and DNA damage induced by iron nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H(2)O(2)). Fe-NTA is a potent nephrotoxic agent and induces acute and subacute renal proximal tubular necrosis by catalyzing the decomposition of H(2)O(2)-derived production of hydroxyl radicals, which are known to cause lipid peroxidation and DNA damage. Incubation of postmitochondrial supernatant and/or calf thymus DNA with H(2)O(2) (40 mM) in the presence of Fe-NTA (0.1 mM) induces lipid peroxidation and DNA damage to about 2.3-fold and 2.9-fold, respectively, as compared to control (P < 0.05). In lipid peroxidation protection studies, S. crispus treatment showed a dose-dependent inhibition (45-53% inhibition, P < 0.05) of Fe-NTA and H(2)O(2) induced lipid peroxidation. Similarly, in DNA damage protection studies, S. crispus treatment also showed a dose-dependent inhibition (18-30% inhibition, P < 0.05) of DNA damage. In addition, the protection was closely related to the content of phenolic compounds as evident by S. crispus extract showing the value of 124.48 mg/g total phenolics expressed as gallic acid equivalent (GAE, mg/g of extract). From these studies, it is concluded that S. crispus inhibits peroxidation of membrane lipids and DNA damage induced by Fe-NTA and H(2)O(2) and possesses the potential to be used to treat or prevent degenerative diseases where oxidative stress is implicated.
Probucol is a clinically used cholesterol-lowering drug, with pronounced antioxidant properties. We have reported previously, that dietary supplementation of probucol enhances NAD(P)H:quinone reductase (Iqbal M, Okada S (2003) Pharmacol Toxicol 93:259-263) and inhibits Fe-NTA induced lipid peroxidation and DNA damage in vitro (Iqbal M, Sharma SD, Oakada (2004) Redox Rep 9:167-172). Further to this, in the present study, we evaluated the modulatory effect of probucol on iron nitrilotriacetae (Fe-NTA) dependent renal carcinogenesis, hyperproliferative response and oxidative stress. In Fe-NTA alone treated group, a 20% renal cell tumor incidence was recorded whereas, in N-diethylnitrosamine (DEN)-initiated and Fe-NTA promoted animals, the percentage tumor incidence was increased to 70% as compared with untreated controls. No tumor incidence was recorded in DEN-initiated, nonpromoted group. Diet supplemented with 1.0% probucol fed prior to, during and after Fe-NTA treatment in DEN-initiated animals afforded >65% protection in renal cell tumor incidence. Probucol fed diet pretreatment also resulted a significant and dose dependent inhibition of Fe-NTA induced renal ornithine decarboxylase (ODC) activity. In oxidative stress studies, Fe-NTA alone treatment enhanced lipid peroxidation, accompanied by a decrease in the level of GSH, activities of antioxidants and phase II metabolizing enzymes in kidney concomitant with histolopathological changes. These changes were significantly and dose-dependently alleviated by probucol fed diet. From this data, it can be concluded that probucol can modulates toxic and tumor promoting effects of Fe-NTA and can serve as a potent chemopreventive agent to suppress oxidant induced tissue injury and carcinogenesis, in addition to being a cholesterol lowering and anti-atherogenic drug.