ABSTRACT
BACKGROUND: Benzo(a)pyrene [B(a)P] is an environmental contaminant and potential carcinogenic agent that causes lung injuries which leads to lung cancer. Rutin, a well-known flavonoid present in various natural sources, possesses biological activities such as anti-oxidative and anti-inflammatory properties. The aim of this study was to evaluate the protective effects of rutin against B(a)P-induced genotoxicity, oxidative stress, apoptosis and inflammation in Swiss albino mice. METHODS: Pretreatment of rutin was given by oral gavage at doses of 40 and 80 mg/kg body weight (b.wt.) for 7 days before the administration of a single oral dose of B(a)P (125 mg/kg b.wt.). The ameliorative effect of rutin on oxidative stress, apoptotic and inflammatory markers in lung tissues and genotoxicity was studied using an alkaline unwinding assay and DNA fragmentation. RESULTS: B(a)P enhanced lipid peroxidation, xanthine oxidase, H2O2 generation and lactate dehydrogenase (LDH) activity; depleted activities of anti-oxidant enzymes and glutathione content; induced DNA strand breaks and fragmentation; disrupted normal histopathological architecture and also showed abnormal expression of NF-κB, COX-2, IL-6, TNF-α and Bcl-2. Rutin pretreatment caused a significant reduction in lipid peroxidation and LDH activity; increased glutathione content; restored antioxidant enzyme activity; reduced DNA strand breaks and fragmentation; modulated the expression of inflammatory, and apoptotic markers and restored the histopathological structure. CONCLUSIONS: The findings of the present study supported the protective effect of rutin against B(a)P-induced lung toxicity and genotoxicity.
Subject(s)
Antioxidants/pharmacology , Oxidative Stress/physiology , Pneumonia/prevention & control , Rutin/pharmacology , Animals , Apoptosis/drug effects , Benzo(a)pyrene/toxicity , Carcinogens/toxicity , Cyclooxygenase 2/metabolism , DNA/drug effects , Hydrogen Peroxide/metabolism , Interleukin-6/metabolism , L-Lactate Dehydrogenase/drug effects , Male , Malondialdehyde/metabolism , Mice , NF-kappa B/metabolism , NF-kappa B/physiology , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-bcl-2/physiology , Superoxide Dismutase/drug effects , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/physiologyABSTRACT
Skin cancer is the most common malignancy in the world and also one of the major causes of death worldwide. The toxic environmental pollutant 7,12-dimethylbenz[a]anthracene (DMBA) is a skin-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemical-induced toxicities and carcinogenesis as well. In the present study, we have evaluated the therapeutic potential of tannic acid in DMBA + croton oil-induced skin cancer in Swiss albino mice. Protective effect of TA against skin cancer was evaluated in terms of antioxidant enzymes activities, lipid peroxidation, histopathological changes and expression of inflammation and early tumour markers. DMBA + croton oil causes depletion of antioxidant enzymes (p < 0.001) and elevation of early inflammatory and tumour promotional events. TA prevents the DMBA + croton oil-induced toxicity through a protective mechanism that involves the reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression and level of proinflammatory cytokine such as IL-6 release at a very significant level (p < 0.001). It could be concluded from our results that TA attenuates DMBA + croton oil-induced tumour promotional potential possibly by inhibiting oxidative and inflammatory responses and acts as antioxidant, anti-inflammatory and antiproliferative agent.
Subject(s)
Anticarcinogenic Agents/pharmacology , Skin Neoplasms/drug therapy , Tannins/pharmacology , 9,10-Dimethyl-1,2-benzanthracene , Animals , Anticarcinogenic Agents/therapeutic use , Croton/chemistry , Cyclooxygenase 2/metabolism , Disease Progression , Drug Evaluation, Preclinical , Female , Glutathione/metabolism , Hydrogen Peroxide/metabolism , Interleukin-6/metabolism , Lipid Peroxidation , Mice , Nitric Oxide Synthase Type II/metabolism , Plant Oils , Proliferating Cell Nuclear Antigen/metabolism , Skin/drug effects , Skin/metabolism , Skin/pathology , Skin Neoplasms/chemically induced , Skin Neoplasms/pathology , Tannins/therapeutic use , Xanthine Oxidase/metabolismABSTRACT
OBJECTIVE: The present study was designed to investigate underlying molecular mechanism for antitumorigenic potential of Terminalia chebula (TC) against chemically-induced skin tumorigenesis in Swiss albino mice. It is used as herbal medicine because it exhibits antioxidant, anti-inflammatory, and anticarcinogenic activity. However, the précised underlying mechanism remains to be elucidated. MATERIALS AND METHODS: In light of the important role of nuclear factor-kappaB (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (i-NOS), ornithine decarboxylase (ODC), proinflammatory cytokines, oxidative stress in carcinogenesis, chemopreventive efficacy of TC against 7,12-dimethylbenz[a] anthracene (DMBA), and croton oil-induced 2-stage skin carcinogenesis was studied in terms of cytoprotective antioxidant enzymes activity, lipid peroxidation (LPO), inflammatory responses, and expression of various molecular markers in skin tissues. RESULTS: We found that topical application of TC at dose of 30 mg/kg b. wt. mouse effectively suppressed oxidative stress and deregulated activation of inflammatory mediators and tumorigenesis. Histological findings further supported the protective effects of TC against DMBA/croton oil-induced cutaneous damage. CONCLUSION: The findings of the present study suggest that the chemopreventive effect of TC is associated with upregulation of endogenous cytoprotective machinery and downregulation of inflammatory mediators (interleukin (IL)-6, COX-2, i-NOS, ODC, and NF-κB).