ABSTRACT
BACKGROUND: Over the past several years, the considerable attention has been progressively given to liposomal formulations of anthracyclines. SinaDoxosome(®) (Exir Nano Sina Company, Iran) is a pegylated liposomal doxorubicin (DOX) which approved by Food and Drug Administration of IRAN for treatment of some types of cancer. The aim of this study was to compare the biodistribution, efficacy, cardiotoxicity and hepatotoxicity of SinaDoxosome(®) with Caelyx(®) in mice bearing C-26 colon carcinoma. METHODS AND RESULTS: Mice tumor size evaluation during the experimental period (28 days) showed comparable therapeutic efficacy of nano-formulations. The biodistribution studies showed no significant difference in DOX tissue concentration between Caelyx(®) and SinaDoxosome(®). DOX induced-ECG changes were not detected in nano-formulations. No significant alteration was found in biochemical indexes of myocardial injury in mice exposed to nano-formulations in comparison with control mice. The tissue oxidative parameters such as lipid peroxidation, glutathione, catalase and superoxide dismutase was significantly changed as the results of free DOX treatment. However, the oxidative status of Caelyx(®) and SinaDoxosome(®) treated animals did not showed any changes. The experiment also revealed that apoptotic pathway was not activated in the heart of mice exposed to nano-formulations. CONCLUSIONS: Although this investigation showed that Caelyx(®) and SinaDoxosome(®) are similar in terms of biodistribution, efficacy and toxicity, appropriate clinical evaluations in patients should be considered.
Subject(s)
Colonic Neoplasms/drug therapy , Colonic Neoplasms/metabolism , Doxorubicin/analogs & derivatives , Xenograft Model Antitumor Assays , Animals , Antibiotics, Antineoplastic , Apoptosis/drug effects , Cell Line, Tumor , Doxorubicin/adverse effects , Doxorubicin/pharmacokinetics , Doxorubicin/therapeutic use , Humans , Liver/metabolism , Male , Mice , Myocardium/metabolism , Myocardium/pathology , Oxidative Stress/drug effects , Particle Size , Polyethylene Glycols/adverse effects , Polyethylene Glycols/pharmacokinetics , Polyethylene Glycols/therapeutic use , Tissue DistributionABSTRACT
There are increasing concerns regarding the toxic effects of chlorpyrifos (CPF) on human health. Curcumin (CUR) is a yellow pigment isolated from turmeric ground rhizome of Curcuma longa Linn., which has been identified as an antioxidant agent. This study was designed to examine the protective effect of CUR and vitamin E (Vit E) on CPF-induced lung toxicity. Rats were divided into seven groups: control, CPF (13.5 mg/kg, orally), CPF + CUR (100 and 300 mg/kg, respectively, orally), CPF + α-tocopherol (Vit E, 150 mg/kg, intraperitoneally), CPF and CUR (100 and 300 mg/kg, respectively) in combination with α-tocopherol. The regimens were administered once daily for 28 days. At the end of the treatment period, lungs were collected for evaluation of oxidative factors and histopathological parameters. CUR and Vit E led to a decrease in lipid peroxidation in the lungs of the CPF-injected animals (48% and 51%, respectively). Glutathione peroxidase inhibited by CPF (91.9 nmol/min/mg protein) was induced again by CUR and Vit E (167.1 and 171.8 nmol/min/mg protein). CUR and Vit E caused a significant induction of superoxide dismutase (103.4 U/mg protein). Catalase activity almost returned to normalcy in CPF-intoxicated rats subjected to CUR + Vit E treatment (p < 0.001). Lung sections from CPF-treated rats displayed histopathological damages, while coadministration of CUR and Vit E resulted in apparently normal morphology with a significant decrease in injuries (p < 0.05). Our findings revealed that coadministration of Vit E and CUR to CPF-treated animals prevents the oxidative damages in the lung tissues.
