D-Aminoacid oxidase (DAO) was isolated from fresh porcine kidney; its cytotoxic potential was studied under in vitro and in vivo conditions. The isolated DAO was complexed with Fe 2 O 3 nanoparticles and its potential as an oxidation therapeutic agent was analysed. The ability of the complex in eliciting H 2 O 2 mediated cytotoxicity was studied on Dalton's lymphoma ascites cells (DLA). The induction of apoptosis in DLA cells by Fe 2 O 3 -DAO complex was studied by morphological examination and alkaline single cell gel electrophoresis (comet assay). The antitumor activity of the complex was investigated by oral administration of the complex and the substrate D-alanine to tumor bearing Swiss albino mice and by targeting the complex to the tumor site, using an externally applied magnetic field. Fe 2 O 3 -DAO along with D-alanine showed remarkable cytotoxicity in a substrate concentration-dependent manner. Both morphological examination and comet assay revealed that Fe 2 O 3 -DAO/D-alanine induced apoptosis. Oral administration of Fe 2 O 3 -DAO and D-alanine along with magnetic targeting significantly suppressed tumor growth in mice. The present report provides the first evidence for the promising application of enzyme bound nanoparticles for targeted oxidation therapy.
Doxorubicin (DOX) is one of the most effective anticancer therapeutic but its use is limited by cardiotoxicity.The generation of reactive oxygen species (ROS) and mitochondrial dysfunction have been implicated in DOX-induced cardiotoxicity. Cardiotoxicity was induced in tumor bearing mice by a single dose of DOX (25mg/kg, i.p). Ferulic acid (FA) (100 mg/kg p.o and 200 mg/kg p.o) was administered one hour after DOX administration. The administration of FA significantly protected the myocardium from the toxic effects of DOX by reducing the levels of serum marker enzymes like CK and LDH and other serum enzymes SGOT and SGPT, which were elevated during DOX induced cardiomyopathy. The level of HDL was also significantly increased in FA administered groups compared to DOX control. FA protected the cardiac tissues, whereas it potentiated the anticancer efficacy of DOX in tumor tissues as evident from different antioxidant enzyme levels and the extent of lipid peroxidation. The histopathological observations also supported these results. FA effectively protected cellular DNA in heart tissue preferentially, without offering any protection to the DNA in tumour tissues as evidenced from the comet assay. These results suggest that ferulic acid has a protective effect against cardiotoxicity induced by DOX and it may, therefore improve the chemotherapeutic index of DOX.
Ferulic acid is an abundant phytophenolic compound present in plant cell wall. Ferulic acid possess anticancer, antioxidant, and anti-aging properties. A simple, sensitive and reproducible spectrophotometric method has been developed for quantitative estimation of ferulic acid from selected plant materials such as rice bran, wheat bran and bamboo shoot. The blue coloured chromogen obtained after the reaction was measured at wavelength of 718 nm for ferulic acid against the blank reagent. The chromogen obeyed linearity over the range of 1?g/ml - 8?g/ml. An HPLC method was also developed for the estimation of ferulic acid from selected plant materials.
Cisplatin (Cis) is one of the most widely used cytotoxic therapeutic agents for the treatment of cancer. Overdose of the drug resulted in various side effects of genotoxicity and nephrotoxicity. The toxicity of the drug has been attributed to the generation of oxidative free radicals. The current study aims to explore the effect of Ferulic acid (FA) in ameliorating Cis-induced renal toxicity in tumor bearing Swiss albino mice. Nephrotoxicity was induced in tumor bearing mice by a single dose of Cis (12mg/kg, i.p). Post administration of FA was carried out (100 mg/kg p.o and 200 mg/kg p.o) one hour after Cis administration. Toxicity was measured by analyzing the amount of serum urea, creatinine, and antioxidant status of renal and tumor tissues. Treatment of cisplatin-administered tumor animals with the FA could prevent the drug-induced oxidative damage as evidenced by the decreased levels of lipid peroxidation and enhanced activities of the antioxidants in the renal tissues. The treatment also protected the renal tissues from the toxic effects of Cis by reducing the levels of serum urea and creatinine. FA protected the renal tissues, whereas it enhanced the anticancer efficacy of Cis in tumor tissues. The histopathological observations support that ferulic acid has a protective effect against Cisplatin-induced nephrotoxicity and can be used to improve the chemotherapeutic index of Cisplatin for cancer treatment.
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