Pyrene-induced Lung Carcinogenesis Research Articles

Effect of mangiferin on benzo(a)pyrene induced lung carcinogenesis in experimental Swiss albino mice

The present study is an effort to identify a potent chemopreventive agent against cancer, in which oxidative stress plays an important causative role. The modulatory effect of mangiferin on mitochondrial lipid peroxidation (LPO), tricarboxylic acid (TCA) cycle key enzymes and electron transport chain complexes was investigated against lung carcinogenesis induced by benzo(a)pyrene (50 mg kg−1 b/w orally) in Swiss albino mice. Decreased activities of electron transport chain complexes and TCA cycle key enzymes such as isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and alpha-ketoglutarate dehydrogenase (α-KGDH), in lung cancer bearing animals were observed. Pre- and post-treatment with mangiferin (100 mg kg−1 b/w orally) for 18 weeks, prevented the above biochemical changes, which were inclined towards normal control animal values. This study further confirms the chemopreventive and chemotherapeutic effect of mangiferin and these results are consistent with our hypothesis that mangiferin is a promising chemopreventive agent.

Rehabilating Activity of Mangiferin in Benzo(a) Pyrene Induced Lung Carcinogenesis

Rehabilating Activity of Mangiferin in Benzo(a) Pyrene Induced Lung Carcinogenesis

Protective Role of Mangiferin against Benzo(a)pyrene Induced Lung Carcinogenesis in Experimental Animals

In recent years, considerable emphasis has been focused on identifying new chemopreventive agents which could be useful for the human population. In the present study, we examined the protective role of mangiferin during experimental lung carcinogenesis with reference to its effect on DNA-damage and the detoxification enzyme system. The activities of detoxifying enzymes such as glutathione transferase (GST), quinone reductase (QR) and uridin 5'-diphosphate-glucuronosyl transferase (UDP-GT) were found to be decreased while the lipid peroxidation level was increased in the lung cancer bearing animals. Supplementation of mangiferin (100 mg/kg b.wt) enhanced the detoxification enzymes and reduced DNA damage as determined by single cell electrophoresis. Furthermore, the DNA-protein cross links which was found to be high in lung cancer bearing animals was also modulated upon supplementation with mangiferin. Our present results explain the unique association between the anti-oxidant effect of mangiferin and ultimately the capability of mangiferin to prevent cancer.

Effect of Crocetin on Benzo (a) Pyrene Induced Lung Carcinogenesis in Swiss Albino Mice

Effect of Crocetin on Benzo (a) Pyrene Induced Lung Carcinogenesis in Swiss Albino Mice

Amelioration of benzo ( a) pyrene-induced lung carcinogenesis in strain A mice by diphenylmethyl selenocyanate

Organoselenocyanates are an important class of chemopreventive agents, which possess antioxidative, antimutagenic and anticarcinogenic properties. In the present study, we used benzo ( a) pyrene (BP)-induced lung carcinogenesis model for assessment of the chemopreventive efficacy of diphenylmethyl selenocyanate, a synthetic organoselenocyanate. BP was given at a dose of 0.2 mg/mouse to initiate lung carcinogenesis in strain A mouse and the Se compound was given orally at a dose of 3 mg/kg b.w. Histopathological characterizations and biochemical estimation were done to determine the protective effect of Se compound during the progression of lung carcinogenesis. Hyperplasia and severe dysplasia, the precancerous stage, were evident in carcinogen control group after 8th and 22nd week, respectively. These times were selected as the targets for chemoprevention. Treatment with the Se compound effectively reduced the incidence of hyperplasia and severe dysplasia. The Se compound also significantly ( p<0.01) reduced microsomal lipid peroxidation and induced glutathione- S-transferase activity in liver and lung when measured after 8th and 22nd week. Lung cancer is diagnosed in majority of cases only at a later stage. These findings will further strengthen the view on organoselenocyanate as an effective cancer chemopreventive agent against lung carcinogenesis when applied at the post-initiation phase.

In vivo effect of piperine on serum and tissue glycoprotein levels in benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice

In recent years, considerable emphasis has been focused on identifying new cancer chemopreventive agents, which could be useful for the human population. Piperine is a pure, pungent alkaloid constituent of black and long peppers ( Piper nigrum and Piper longum), that acts as an antioxidant and anticancer agent by its numerous macromolecules associated with them. In the present study, piperine was found to suppress benzo(a)pyrene (B(a)p) induced lung cancer in Swiss albino mice. In lung cancer bearing mice, altered levels of total protein and protein bound carbohydrate components (hexose, hexosamine and sialic acid) were observed in serum, lung and liver tissues. Dietary supplementation of piperine (50 mg/kg body weight) to B(a)p administered animals decreased the total protein and protein bound carbohydrate levels of lung cancer bearing animals in during initiation and post-initiation phases. Our data suggest that piperine may extend its chemopreventive effect through modulating the protein bound carbohydrate levels, as they are one of the indicators of tumorigenesis.

Black tea polyphenols suppress cell proliferation and induce apoptosis during benzo(a)pyrene-induced lung carcinogenesis

One of the most promising strategies for cancer prevention is chemoprevention by daily used food and beverages. Black tea, the most widely consumed beverage, is a source of compounds with antioxidative, antimicrobial, antimutagenic and anticarcinogenic properties. Lung cancer is the most common cause of cancer deaths in both men and women worldwide. Over one million people around the world are likely to be killed by lung cancer due to increased tobacco smoking and environmental pollutants, especially car exhausts. Therefore chemopreventive intervention using black tea and its active components may be a viable means to reduce lung cancer death. In the present investigation, we used benzo(a)pyrene (BP) to induce lung carcinogenesis in mice for the assessment of potential apoptosis-inducing and proliferation-suppressing effects of theaflavins and epigallocatechin gallate, active components of black tea. Hyperplasia, dysplasia and carcinoma in situ evident in the carcinogen control group on the 8th, 17th and 26th weeks respectively, were effectively reduced after treatment with theaflavins and epigallocatechin gallate. Significant reduction in number of proliferating cells and increased number of apoptotic cells was also found on the 8th, 17th and 26th week of treatment with theaflavins and epigallocatechin gallate in BP-exposed mice. Our observation suggests a promising role for black tea polyphenols in the prevention of lung cancer.

Chemopreventive effect of piperine on mitochondrial TCA cycle and phase-I and glutathione-metabolizing enzymes in benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice

Piperine is a major component of black (Piper nigrum Linn) and long pepper (Piper longum Linn) used widely in various systems of traditional medicine. We have evaluated the effect of piperine on mitochondrial tricarboxylic acid cycle and phase I and glutathione-metabolizing enzymes in Benzo(a)pyrene induced experimental lung carcinogenesis in swiss albino mice. Lung cancer bearing mice showed a significant decrease in the activities of mitochondrial enzymes-isocitrate dehydrogenase (ICDH), -ketoglutarate dehydrogenase (KDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and significantly increased NADPH-Cytochorome reductase (NADPH-C reductase), cytochrome P450 (cyt-p450) and cytochrome b5(cyt-b5). The activities of glutathione-metabolizing enzymes glutathione peroxidase(GPx), glutathione reductase (GR) and glucose-6-phospho dehydrogenase(G6PDH) were significantly lowered in lung-cancer bearing mice when compared with control mice. Piperine supplementation to tumour-induced animals significantly lowered the phase-I enzymes (NADPH-C reductase, cyt-p450 and cyt-b5)) and there was a rise in glutathione-metabolizing enzymes (GPx, GR and G6PDH), which indicated an antitumour and anti-cancer effect. Comparison of normal control mice and mice administered piperine only as drug control showed no significant variations in enzyme activities. Piprine administration to benzo(a)pyrene induced animals significantly increased the activities of mitochondrial enzymes, thereby suggesting its role in mitochondrial energy production.

Protective effect of piperine on benzo( a)pyrene-induced lung carcinogenesis in Swiss albino mice

Background The statistics on lung cancer necessitates the urge to develop new methods to control this most deadly form of cancer. Chemoprevention is one of these new approaches. Carcinogens from cigarette smoke form the link between nicotine addiction and lung cancer. At the same time, it has become increasingly clear that dietary and genetically determined factors play an important role in modulating the individual susceptibility and are linked to the chemoprevention approach. In this study, the ability of piperine to prevent lung carcinogenesis in mice was characterized and its effects on cell proliferation and protein damage biomarkers were determined. Methods Thirty Swiss albino mice were divided into five groups of six animals each. Animals in group I received corn oil orally and served as control. Group II were administered with 50 mg/kg b.wt. of benzo( a)pyrene (B( a)P) twice a week for 4 consecutive weeks to induce lung cancer by the end of 16th week. Group III received 50 mg/kg b.wt. piperine on alternate days for 16 weeks immediately after the first dose of carcinogen. Group IV also received piperine as in group III but from the sixth week of B( a)P induction till the end of the experiment. Group V animals constituted the drug control and received piperine alone. Results Administration of piperine significantly decreased the levels of lipid peroxidation, protein carbonyls, nucleic acid content and polyamine synthesis that were found to be increased in lung cancer bearing animals. Conclusions Piperine could effectively inhibit B( a)P-induced lung carcinogenesis in albino mice by offering protection from protein damage and also by suppressing cell proliferation.

Chemopreventive effect of piperine on modulating lipid peroxidation and membrane bound enzymes in benzo(a)pyrene induced lung carcinogenesis

The current study was designed to evaluate the effects of oral supplementation of the piperine on lung tumour initiation by orally applied benzo(a)pyrene (B(a)p). To evaluate the effects of orally supplemented piperine on lung tumour initiation by B(a)p, its effects on ATPase enzymes were first evaluated. Lung cancer bearing mice showed an increase in erythrocyte membrane and tissues ATPase enzymes (Na +/K +-ATPases, Mg 2+-ATPases and Ca 2+-ATPases). Na + K-ATPase and Mg-ATPase enzyme activities were decreased and calcium ATPase increased ( P < 0.05) in erythrocyte membrane and tissues of lung cancer bearing animals compared with control groups. The elevation of these enzyme activities in membrane and tissues were indicative of the persistent deteriorating effect of B(a)p in cancer bearing animals. These enzyme activities were reversed to near normal control values in animals treated with piperine (50 mg/kg body weight). It is apparent that the beneficial effect of piperine is primarily exerted on the during initiation phase and post-initiation stage of B(a)p induced lung carcinogenesis. Overall, these data indicative that piperine has chemopreventive effects when administered orally on lung cancer bearing animals.

Effect of cigarette smoke inhalation on benzo[ a]pyrene-induced lung carcinogenesis in vitamin A deficiency in the rat

Vitamin A deficiency caused a significant increase (P < 0.05) in benzo[a]pyrene (BP)-induced lung tumor incidence and tumor burden in male Wistar rats. Inhalation of cigarette smoke during initiation and post-initiation phases of carcinogenesis resulted in higher tumor burden as compared to the same observed in the animals exposed to cigarette smoke during the post-initiation phase only. Stimulation in tumor burden by cigarette smoke was increased further by vitamin A deficiency.

The effect of vitamin A deficiency on the initiation and postinitiation phases of benzo(a)pyrene-induced lung tumourigenesis in rats.

The present investigation shows the effect of vitamin A deficiency on the initiation and postinitiation phases of benzo(a)pyrene-induced lung carcinogenesis in male Wistar rats. Lung tumours were induced by giving three intratracheal instillations, one week apart, of 10 mg benzo(a)pyrene per instillation. Maximum tumour incidence (100%) and tumour burden per rat was found in rats which were kept on vitamin A deficient diet for 4 weeks prior to the first administration and 8 weeks after the last administration of benzo(a)pyrene. Rats in which vitamin A deficiency was terminated after the last administration of the carcinogen had 83% tumour incidence, whereas corresponding control pairfed animals had 39% incidence of tumours. These data represent the values obtained 32 weeks after the last administered dose of the carcinogen and indicate the role of vitamin A, both in the initiation as well as in the postinitiation phases of lung carcinogenesis.

Magnesium Oxide as Carrier Dust in Benzo[&lt;italic&gt;a&lt;/italic&gt;]pyrene-Induced Lung Carcinogenesis in Syrian Hamsters&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;

The neoplastic progression induced by intratracheal instillation of benzo[a]pyrene (BP) and magnesium oxide (MgO) was compared with that induced by intratracheal instillation of BP and ferric oxide (Fe2O3). BP and MgO produced squamous cell carcinomas and papillomas in the larynx with a latent period as shor as 9 weeks. They also induced many papillomas as well as squamous cell carcinomas and adenocarcinomas in the trachea and a papilloma, squamous cell carcinomas, adenocarcinomas, adenosquamous lesions, and peripheral adenomatoid lesions in the bronchi. They rarely caused tumors in other organs; only a few forestomach papillomas, one melanoma on the dorsal skin, and one ovarian carconoma were seen BP, with Fe2O3 as the carrier, induced a comparable number of histologically similar tumors; however, tumors developed more frequently in the main bronchi. Thus MgO strongly facilitated the tumor-inducing effects of BP, causing tumors in different areas of the respiratory tract, and was as effective as Fe2O3 as a carrier agent in the experimental induction of respiratory tumors.