ABSTRACT
Colon cancer is one of the serious health problems in most developed countries and its incidence rate is increasing in India. Hesperetin (HN) (3',5,7-trihydroxy-4'-methoxyflavonone) and hesperetin analogue (HA) were tested for their apoptosis inducing ability. Methyl thiazolyl tetrazolium assay revealed a dose as well as duration-dependent reduction of HT-29 (colon adenocarcinoma) cellular growth in response to HN and HA treatment. At 24 h 70 µM of HN and 32 µM of HA showed 50% reduction of HT-29 cellular growth. Acridine orange/ethidium bromide staining showed apoptotic features of cell death induced by HN and HA. Rhodamine 123 staining showed significant reduction in mitochondrial membrane potential induced by HN and HA. HN and HA induced DNA damage was confirmed by comet tail formation. Lipid peroxidation markers (TBARS) and protein oxidation marker (PCC) were significantly elevated in HN and HA treated groups. Enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were slightly decreased in their activities compared to control (untreated HT-29 cells). Results of Western blot analysis of apoptosis associated genes revealed an increase in cytochrome C, Bax, cleaved caspase-3 expression and a decrease in Bcl-2 expression. These findings indicate that HN and HA induce apoptosis on HT-29 via Bax dependent mitochondrial pathway involving oxidant/antioxidant imbalance.
Subject(s)
Adenocarcinoma/pathology , Apoptosis/drug effects , Colonic Neoplasms/pathology , Hesperidin/pharmacology , Adenocarcinoma/enzymology , Adenocarcinoma/metabolism , Catalase/metabolism , Colonic Neoplasms/enzymology , Colonic Neoplasms/metabolism , DNA Damage , Glutathione Peroxidase/metabolism , HT29 Cells , Humans , Lipid Peroxidation , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolism , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
The present study was aimed to evaluate the radioprotective efficacy of hesperidin, a flavonone glycoside against X-ray radiation-induced cellular damage in the liver of Swiss albino mice. The first phase of the study was carried out to fix the effective concentration of hesperidin by performing a 30 days of survival studies using different graded doses [12.5, 25, 50 and 100mg/kg body weight] of hesperidin administered orally to mice via intragastric intubations for seven consecutive days prior to exposure of whole body radiation (10 Gy). Based on the results of survival studies, the effective dose of hesperidin was fixed which was then administered to animals orally via intragastric intubations for seven consecutive days prior to exposure of whole body radiation (4 Gy) to evaluate its radioprotective efficacy by performing various biochemical estimations, comet assay, DNA fragmentation assay and histopathological studies in the liver of Swiss albino mice. The results indicated that radiation-induced decrease in the levels of endogenous antioxidant enzymes and increase in lipid peroxidative index, DNA damage and comet parameters were altered by pre-administration with the effective dose of hesperidin [25mg/kg body weight] which restored the antioxidant status to near normal and decreased the levels of lipid peroxidative index, DNA damage and comet parameters. These results were further confirmed by histopathological examinations which indicated that pre-administration with the effective dose of hesperidin reduced the hepatic damage induced by radiation. Thus the current study shows hesperidin to be an effective radioprotector against radiation induced damage in the liver of mice.
Subject(s)
Hesperidin/pharmacology , Liver/drug effects , Liver/radiation effects , Radiation-Protective Agents/pharmacology , Animals , Antioxidants/metabolism , Comet Assay , DNA Fragmentation/drug effects , DNA Fragmentation/radiation effects , Lipid Peroxidation/drug effects , Lipid Peroxidation/radiation effects , Liver/metabolism , Liver/pathology , Male , Mice , Survival Rate , X-Rays/adverse effectsABSTRACT
This investigation aims to evaluate the antitumor and antioxidant potential of Chrysaora quinquecirrha (sea nettle) nematocyst venom on Ehrlich ascites carcinoma (EAC) tumor model. Tumor was induced in mice by intraperitoneal injection of EAC cells. The antitumor effect of sea nettle nematocyst venom (SNV) peptide was evaluated by assessing in vitro cytotoxicity, survival time, hematological, and antioxidant parameters. Intraperitoneal injection of SNV peptide increased the survival time of the EAC-bearing mice. The SNV peptide brought back the altered levels of the hematological and antioxidant parameters in a dose dependent manner in EAC-bearing mice. The results were comparable to that of the result obtained from the animals treated with the standard drug 5-fluorouracil (20 mg/kg bw). Thus, present study revealed that SNV peptide possessed significant antitumor and antioxidant activity.
