ABSTRACT
2-Acetylaminofluorene (2-AAF) is a known hepatic carcinogen which leads to tumour formation in rodents. 18-ß Glycyrrhetinic acid (18ß-GA) derived from liquorice plant has various pharmacological properties such as anti-ulcer, anti-inflammatory, antiviral, hepatoprotective and antioxidant. This study is designed to elucidate the chemopreventive properties of 18ß-GA against 2-AAF-induced liver toxicity in Wistar rats and evaluated its effect on inflammatory and tumour promotion marker and activities of different oxidative stress enzymes. Administration of 2-AAF at the dose of (50 mg/kg body weight (b.w.) intraperitoneally (i.p.)) for five consecutive days induces hepatic toxicity, inflammation, oxidative stress and hyperproliferation. Pretreatment with 18ß-GA at two different doses (45 and 75 mg kg(-1) b.w.) significantly ameliorates 2-AAF-induced increased lipid peroxidation, alanine transaminase and aspartate transaminase, xanthine oxidase activities and activities of phase-II detoxifying enzymes along with the levels of glutathione content. Administration of 18ß-GA also significantly restored the expressions of proliferating cell nuclear antigen, cyclooxygenase 2, inducible nitric oxide synthase and nuclear factor κB. Furthermore, histological observations also support the preventive effects of 18ß-GA. Our findings suggest that pretreatment with 18ß-GA showed potential hepatoprotective effects via attenuation of oxidative stress, inflammation and hyperproliferation.
Subject(s)
Chemical and Drug Induced Liver Injury/drug therapy , Glycyrrhetinic Acid/therapeutic use , Protective Agents/therapeutic use , 2-Acetylaminofluorene/toxicity , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Catalase/metabolism , Cell Proliferation/drug effects , Chemical and Drug Induced Liver Injury/metabolism , Cyclooxygenase 2/metabolism , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Glutathione Transferase/metabolism , Glycyrrhetinic Acid/pharmacology , Inflammation/metabolism , Lipid Peroxidation/drug effects , Male , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Oxidative Stress/physiology , Proliferating Cell Nuclear Antigen/metabolism , Protective Agents/pharmacology , Rats, Wistar , Xanthine Oxidase/metabolismABSTRACT
Studies on loss of heterozygosity have been made for Parkin gene-specific microsatellite markers in malignancies like breast, ovary and lungs, and the results have shown a significant association. However, till date, there is no study with respect to Parkin gene-associated microsatellite markers in cervical cancer. The present study deals with the Parkin gene-associated microsatellite markers and the occurrence of its loss of heterozygosity in patients with human cervical cancer. DNA was isolated from the 105 cervical carcinoma samples and matched control specimens. Polymerase chain reaction was performed using primer specific for two intragenic markers D6S1599 and D6S305 present in Parkin introns 2 and 7, respectively, and one marker (D6S1008) at telomeric end and further electrophoresed on 8% denaturing polyacrylamide gel. Overall, 59 of 105 (56%) samples showed loss of heterozygosity in at least one locus in the region examined. The percentage of loss of heterozygosity for these markers ranged from 25% (D6S1008) to 48% (D6S305). Chi-square test was performed, and loss of heterozygosity was found significantly higher in both the intragenic markers (D6S1599 and D6S305) when compared with the locus at telomeric end (D6S1008) with P<0.05. These data argue that Parkin is a tumor suppressor gene whose inactivation may play an important role in the carcinoma of uterine cervix.
