Epoxidation of Argemone mexicana oil with peroxyacetic acid formed in-situ using sulfated tin (IV) oxide catalyst: Characterization; kinetic and thermodynamic analysis.

In this study, sulfated tin (IV) oxide solid acid catalyst was prepared for the epoxidation of Argemone mexicana oil (AMO) with peroxyacetic acid formed in-situ. The catalyst was synthesized using the chemical co-precipitation method and characterized. The effects of various epoxidation parameters on ethylenic double bond conversion (%) and oxygen ring content were analyzed. The maximum ethylenic double bond conversion of 95.5% and epoxy oxygen content of 6.25 was found at the molar ratio of AMO to 30% of H2O2 = 1:2.5, molar ratio of AMO to acetic acid = 1:1.5, catalyst concentration = 12.5%, and reaction temperature = 70 °C at reaction time = 6 h. The kinetic and thermodynamic features of the epoxidation of AMO were also analyzed with appropriate models. The results of the kinetic study of the epoxidation reaction followed pseudo first order with the activation energy = 0.47.03 kJ/mol. Moreover, the thermodynamic constants of epoxidation of AMO were found as ΔH = 44.18 kJ/mol, ΔS = -137.91 Jmol-1k-1) and ΔG = 91.12 kJ/mol. The epoxidized product of AMO was further analyzed using FTIR, 1H NMR, and 13C NMR. The results of these analyses confirmed the successful conversion of the ethylenic double bond in the AMO to EAMO.

Protective effect of berberine on expression pattern of apoptotic, cell proliferative, inflammatory and angiogenic markers during 7,12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis.

Investigation of expression pattern of molecular markers in oral epithelial tissues would help to assess the cell differentiation and proliferation as well as early diagnosis of precancerous and cancerous lesions of the oral cavity. Aim of the present study was to investigate the protective effect of berberine on expression pattern of apoptotic, cell proliferative, inflammatory and angiogenic markers during 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Immunohistochemical staining [p53, Bcl-2, Bax, Proliferating Cell Nuclear Antigen (PCNA) and Vascular Endothelial Growth Factor (VEGF)], Enzyme Linked Immuno Sorbent Assay (ELISA) [c-fos, COX-2, caspase-3 and -9] and Real-Time PCR [Cyclin D1 and NFkappaB] were utilized to assess the expression pattern of molecular markers in DMBA induced hamster buccal pouch carcinogenesis. Over expression of mutant p53, PCNA, Bcl-2 and VEGF were noticed in hamsters treated with DMBA alone. Decreased expression of Bax protein was noticed in hamsters treated with DMBA alone. Increased expression of C-fos, COX-2, NFkappaB and Cyclin D1 and decreased activities of caspase-3 and -9 were also noticed in hamsters treated with DMBA alone. Oral administration ofberberine at a dose of 75 mg kg(-1) b.w. brought back the expression of above mentioned molecular markers to near normal pattern in hamsters treated with DMBA. The present results thus suggest that berberine has potent anti-inflammatory, anti-angiogenic, anti-cell proliferative and apoptosis inducing properties in DMBA induced oral carcinogenesis.

Effect of curcumin and ferulic acid on modulation of expression pattern of p53 and bcl-2 proteins in 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.

The modulating effect of curcumin and ferulic acid was investigated on expression pattern of apoptosis regulatory p53 and bcl-2 proteins in oral squamous cell carcinoma (OSCC). The OSCC was induced in the buccal pouch of golden Syrian hamster by painting with 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) three-times a week for 14 weeks. The expression pattern of p53 and bcl-2 proteins was analyzed by immunohistochemical staining. We noticed 100% tumor formation in hamsters painted with DMBA alone for 14 weeks. Overexpression of p53 and bcl-2 proteins was observed in the buccal mucosa of tumor-bearing hamsters. Oral administration of curcumin (80 mg/kg body wt) and ferulic acid (40 mg/kg body wt) to DMBA painted hamsters on days alternate to DMBA painting for 14 weeks completely inhibited tumor formation and down-regulated the expression pattern of p53 and bcl-2 proteins. Our results thus demonstrated the protective role of curcumin and ferulic acid on DMBA-induced abnormal expression of p53 and bcl-2 proteins in the buccal mucosa of golden Syrian hamsters.

Chemopreventive potential of ferulic acid in 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in Sprague-Dawley rats.

Aim of the present study was to investigate the chemopreventive potential of ferulic acid on 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary carcinogenesis in Sprague-Dawley rats. The chemopreventive potential of ferulic acid was assessed by monitoring the tumor incidence, as well as analyzing the status of biochemical (enzymatic and non-enzymatic antioxidants and phase II detoxification enzymes) and molecular (p53 and bcl-2) markers during DMBA-induced mammary carcinogenesis. Mammary carcinogenesis was induced in Sprague-Dawley rats by providing a single subcutaneous injection of 25 mg of DMBA in 1 ml emulsion of sunflower oil (0.75 ml) and physiological saline (0.25 ml) to each rat. Oral administration of ferulic acid at a dose of 40 mg/kg body weight to rats treated with DMBA significantly prevented the tumor formation in 80% of animals (8/10). Also, oral administration of ferulic acid significantly protected the biochemical and molecular abnormalities in DMBA treated rats. Although the exact mechanism for the chemopreventive potential of ferulic acid in DMBA-induced mammary carcinogenesis is unclear, its antigenotoxic and antioxidant potential as well as modulatory effect on phase II detoxification cascade could play a possible role.

Anti-clastogenic potential of carnosic acid against 7,12-dimethylbenz(a)anthracene (DMBA)-induced clastogenesis.

Carnosic acid, a primary phenolic compound found in the leaves of rosemary (Rosmarinus officinalis), has diverse pharmacological and biological activities. The aim of the present study was to investigate the anti-clastogenic effect of carnosic acid in DMBA-induced clastogenesis. The frequency of bone marrow micronucleated polychromatic erythrocytes (MnPCEs), chromosomal aberrations (cytogenetic end points), the status of Phase I and II detoxification enzymes, lipid peroxidation by-products and antioxidants (biochemical endpoints) were analyzed to assess the anti-clastogenic effect of carnosic acid in DMBA-induced clastogenesis. Oral pretreatment of carnosic acid for five days to DMBA-treated hamsters significantly protected DMBA-induced clastogenesis as well as biochemical abnormalities. Although the exact mechanism of anti-clastogenic effects of carnosic acid is unclear, the antioxidant potential and effect on modulation of Phase I and II detoxification enzymes could play a possible role.

Circadian time-dependent chemopreventive potential of withaferin-A in 7,12-dimethylbenz[a]anthracene-induced oral carcinogenesis.

Circadian time-dependent treatment with chemotherapeutic drugs (chronotherapy) optimizes the therapeutic index by maximizing treatment efficacy and minimizing toxicity. The circadian time-dependent chemopreventive and anti-lipid peroxidative efficacy of withaferin-A in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis was investigated in the present study. We induced oral squamous cell carcinoma in the buccal pouches of golden Syrian hamsters during the day (4:00, 8:00, 12:00, 16:00, 20:00 and 24:00) by application of DMBA three times per week for 14 weeks. The circadian time-dependent tumor incidence, volume and burden were observed in hamsters treated with either DMBA alone or DMBA + withaferin-A. The circadian pattern of lipid peroxidation by-products, as measured by the formation of thiobarbituric acid reactive substances (TBARS) and enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)], was also analyzed in the buccal mucosa of DMBA-treated hamsters. We found the highest incidence of tumor formation at 24.00 h in hamsters treated with DMBA alone as compared to other experimental groups. Circadian dysregulation of lipid peroxidation and antioxidant status was observed in DMBA-treated animals as compared to control animals. Oral (po) administration of withaferin-A (20 mg/kg) completely prevented the formation of tumors between 8.00 h and 12.00 h and synchronized the status of lipid peroxidation and antioxidants in the buccal mucosa of hamsters treated with DMBA alone. Also, oral administration of withaferin-A to DMBA-treated animals significantly reduced the formation of tumors and synchronized the status of lipid peroxidation and antioxidants in the rest of the time intervals. Our study thus suggests that withaferin-A has significant chemopreventive and anti-lipid peroxidative potential in DMBA-induced oral carcinogenesis, probably by interfering with DMBA-induced abnormal cell proliferation in the buccal mucosa.

Antigenotoxic effect of genistein against 7,12-dimethylbenz[a]anthracene induced genotoxicity in bone marrow cells of female Wistar rats.

Carcinogen induced mutation in somatic cells leads to genetic instability, which is considered as an important facet of carcinogenesis. Agents that inhibit DNA adduct formation, stimulate DNA repair mechanisms, and possess antioxidant functions are considered as antigenotoxic agents. Genistein, the major isoflavone of soy products, protects animals against experimentally induced mammary and prostate cancers. 7,12-Dimethylbenz[a]anthracene (DMBA), a potent site-specific carcinogen, induce mutations in DNA through its active metabolite, dihydrodiol epoxide, what is a crucial step in cancer initiation. The antigenotoxic effect of genistein against DMBA-induced genotoxicity has been investigated in the present study by analyzing the frequency of micronucleated polychromatic erythrocytes (MnPCEs) and chromosomal aberrations as cytogenetic end-points. The status of lipid peroxidation, antioxidants and detoxication agents were used as biochemical end-points to assess the antigenotoxic effect of genistein. Elevated MnPCEs frequency, marked chromosomal aberrations and enhanced status of lipid peroxidation, antioxidants and detoxication agents were observed in DMBA-treated animals. Oral pretreatment of genistein (20 mg/kg b.w.) for 5 days to DMBA-treated animals significantly reduced the frequency of micronucleus formation and chromosomal abnormalities as well as reversed the status of biochemical variables. Our results suggest that genistein has potent antigenotoxic effect against DMBA-induced genotoxicity.

Protective effect of ferulic acid on 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis in Swiss albino mice.

Our aim was to evaluate and compare the chemopreventive potential of topically applied and orally administered ferulic acid in 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin carcinogenesis. Estimating the status of phase I and phase II detoxication agents, lipid peroxidation byproducts and antioxidants during DMBA-induced skin carcinogenesis assessed the mechanistic pathway for its chemopreventive efficacy. Skin squamous cell carcinoma was induced in the shaved back of mice, by painting with DMBA (25 microg in 0.1 mL(-1) acetone) twice weekly for 8 weeks. We have observed 100% tumor formation in the 15th week of experimental period in mice treated with DMBA alone. Marked alterations in the status of phase I and phase II detoxication agents, lipid peroxidaton byproducts and antioxidants were observed in tumor bearing mice. Oral administration of ferulic acid completely prevented the formation of skin tumors, whereas topically applied ferulic acid did not show significant chemopreventive activity during DMBA-induced mouse skin carcinogenesis. Also, oral administration of ferulic acid reverted the status of phase I and phase II detoxication agents, lipid peroxidaton byproducts and antioxidants to near-normal range in DMBA-treated mice. Our results thus demonstrate that orally administered ferulic acid has potent suppressing effect on cell proliferation during DMBA-induced skin carcinogenesis. This is probably due to its modulating effect on the status of lipid peroxidation, antioxidants and detoxication agents during DMBA-induced skin carcinogenesis.

Chemopreventive potential of piperine in 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis in Swiss albino mice.

The chemopreventive potential of orally administered piperine was studied in Swiss albino mice against 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin carcinogenesis. The mechanistic pathway for the chemopreventive potential of piperine was evaluated by analysing the status of phase I and phase II detoxification agents, lipid peroxidation by-products and antioxidants during DMBA-induced skin carcinogenesis. Skin squamous cell carcinoma was induced in the shaved back of mice, by painting with DMBA (25µg in 0.1ml acetone/mouse) two times weekly for 8 weeks. We observed severe hyperplasia, dysplasia, and well-differentiated squamous cell carcinoma in the 8th, 10th and 15th week of experimental period respectively in mice treated with DMBA alone. Marked alterations in the status of phase I and phase II detoxification agents, lipid peroxidation by-products and antioxidants were observed in tumor bearing mice. Oral administration of piperine (50mgkg(-1) body weight) by gastric gavage significantly prevented the formation of skin tumors during DMBA-induced mouse skin carcinogenesis. Also, piperine administration brought back the status of phase I and phase II detoxification agents, lipid peroxidation by-products and antioxidants to near normal range in DMBA treated mice. The present study thus demonstrates that piperine has significant suppressing effect on cell proliferation during DMBA-induced mouse skin carcinogenesis. The chemopreventive potential of piperine is probably due to its modulating effect on the status of lipid peroxidation, antioxidants and detoxification agents during DMBA-induced skin carcinogenesis.

Ferulic acid inhibits 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis.

The aim of this study was to assess the chemopreventive efficacy of ferulic acid in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. We induced oral squamous cell carcinoma in the buccal pouch of male Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. The tumor incidence, tumor volume, and tumor burden that were formed in the hamster buccal pouch were determined. The activities of carcinogen detoxification agents and status of lipid peroxidation and antioxidants were also estimated by specific colorimetric methods. We observed 100% tumor formation in DMBA-painted animals. The status of carcinogen-detoxifying agents, lipid peroxidation, and antioxidants was significantly disrupted in DMBA-painted animals. Oral administration of ferulic acid at a dose of 40 mg/kg of body weight to DMBA-painted animals on days alternate to DMBA painting for 14 weeks significantly prevented the tumor incidence, tumor volume, and tumor burden. Ferulic acid exhibited potent anti-lipid peroxidative effects as well as the ability to modulate the status of carcinogen-detoxifying agents and antioxidants in DMBA-painted animals. Our results demonstrate that ferulic acid has potent chemopreventive and antioxidant functions in DMBA-induced hamster buccal pouch carcinogenesis.

Clerodendron inerme protects cellular integrity during 7,12-dimethylbenz[A]-anthracene induced hamster buccal pouch carcinogenesis.

Aim of the present study was to investigate the protective effect of Clerodendron inerme on cellular integrity by measuring the status of glycoconjugates, lipids, osmotic fragility, and membrane bound enzyme activity in 7,12-dimethylbenz (a) anthracene (DMBA)-induced oral carcinogenesis. Oral squamous cell carcinoma was induced in the buccal pouch of Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin thrice a week for 14 weeks. The levels of glycoconjugates, lipids, osmotic fragility and membrane bound enzyme activity were analyzed by using specific colorimetric methods. We observed 100% tumor formation in DMBA painted hamsters. Altered glycoconjugates and lipid pattern were observed in DMBA painted hamsters as compared to control hamsters. Erythrocytes from DMBA painted hamsters were more fragile than those from control hamsters. The activity of membrane bound enzyme (Na(+) K(+) ATPase) decreased in DMBA painted hamsters as compared to control hamsters. Oral administration of aqueous leaf extract of Clerodendron inerme (CiALet) at a dose of 500 mg/kg body weight significantly prevented the tumor formation and histopathological abnormalities as well as normalized the above said biochemical variables in DMBA painted hamsters. Our results thus demonstrate the protective effect of Clerodendron inerme on cellular integrity during DMBA induced oral carcinogenesis.

Protective effect of Withaferin-A on micronucleus frequency and detoxication agents during experimental oral carcinogenesis.

Our aim was to investigate the effect of Withaferin-A on bone marrow micronucleus frequency and buccal mucosa detoxication agents during 7, 12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Oral squamous cell carcinoma was developed in hamsters' buccal pouches by painting 0.5% DMBA in liquid paraffin, three times per week for 14 weeks. We observed 100% tumor formation in DMBA painted hamsters. Elevated frequency of bone marrow micronucleated polychromatic erythrocytes (MnPCEs) and decrease in buccal mucosa phase II detoxication agents were noticed in tumor bearing hamsters. Oral administration of Withaferin-A significantly reduced the micronucleus frequency and brought back the status of phase II detoxication agents in DMBA painted hamsters. Our study thus demonstrated the protective effect of Withaferin-A on DMBA-induced micronucleus frequency in the bone marrow of golden Syrian hamsters. Also, Withaferin-A maintained the status of buccal mucosa detoxication agents during DMBA-induced hamster buccal pouch carcinogenesis.

Protective role of Withaferin-A on red blood cell integrity during 7,12-dimethylbenz[a]anthracene induced oral carcinogenesis.

The aim of the present study was to investigate the protective effect of Withaferin-A on red blood cell integrity during 7,12-dimethylbenz[a]anthracene (DMBA) induced oral carcinogenesis. The protective effect of Withaferin-A was assessed by measuring the status of glycoconjugates, membrane bound enzyme activity and red blood cell osmotic fragility. Oral squamous cell carcinoma was induced in the buccal pouch of Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin thrice a week for 14 weeks. The levels of glycoconjugates, membrane bound enzyme activity, osmotic fragility and thiobarbituric acid reactive substances (TBARS) were analyzed by using specific colorimetric methods. We observed 100% tumor formation in DMBA painted hamsters. Increase in plasma glycoconjugates at the expense of red blood cell membrane glycoconjugates levels were observed in DMBA painted hamsters as compared to control hamsters. Erythrocytes from DMBA painted hamsters were more fragile than those from control hamsters. The activity of membrane bound enzyme (Na(+) K(+) ATPase) decreased whereas TBARS level was increased in DMBA painted hamsters as compared to control hamsters. Oral administration of Withaferin-A at a dose of 20 mg kg(-1) bw significantly prevented the tumor formation as well as normalized the biochemical variables in DMBA painted hamsters. Our results thus demonstrate the protective effect of Withaferin-A on red blood cell integrity during DMBA induced oral carcinogenesis.

Chemopreventive and antilipidperoxidative potential of Clerodendron inerme (L) Gaertn in 7,12-dimethylbenz(a)anthracene induced skin carcinogenesis in Swiss albino mice.

The present study has investigated the chemopreventive and antilipidperoxidative effects of the ethanolic extract of Clerodendron inerme leaves (CiELet) in DMBA induced skin carcinogenesis in Swiss albino mice. The skin squamous cell carcinoma was induced in the shaved back of mice, by painting with DMBA (25 microg 0.1 mL(-1) acetone) twice weekly for 8 weeks. We have observed 100% tumor formation in the fifteenth week of experimental period. Elevated lipid peroxidation and decline in enzymatic and non-enzymatic antioxidants status was observed in tumor bearing mice. Oral administration of CiELet (300 mg kg(-1) bw) for 25 weeks significantly prevented the tumor incidence, volume and burden of the tumor. The CiELet also showed potent antilipidperoxidative effect as well as enhanced the antioxidant defense mechanisms in DMBA painted mice. The present study thus demonstrated the chemopreventive and antilipidperoxidative efficacy of CiELet in DMBA induced mouse skin carcinogenesis.