Shanmugam Manoharan

Measurement of erythrocyte lipids, lipid peroxidation, antioxidants and osmotic fragility in cervical cancer patients

BACKGROUND Our aim was to examine the structural integrity of red blood cells in cervical cancer patients by measuring the concentrations of thiobarbituric acid reactive substances (TBARS), antioxidant status, cholesterol/phospholipid (C/P) molar ratio, enzyme activity and osmotic fragility of erythrocytes. METHODS This study has been conducted on 32 adult female cervical cancer patients and an equal number of age- and sex-matched normal subjects. Erythrocyte concentrations of lipids, TBARS, vitamin E, reduced glutathione and enzymic activities of catalase and Na(+)K(+)-ATPase were measured as well as plasma concentrations of sodium and potassium. The present study also examined the changes in erythrocyte osmotic fragility in cervical cancer patients and normal subjects. The red cell fluidity and permeability were determined by estimating the C/P ratio and Na(+)K(+)-ATPase activity, respectively. RESULTS The release of thiobarbituric acid reactive substances was significantly higher in cervical cancer patients as compared to normal subjects. The increased lipid peroxidation with concomitant decrease in antioxidants was notable in cervical cancer patients. Red blood cells of cervical cancer patients were more fragile than those from normal subjects. Increase in red cell membrane C/P ratio and Na(+)K(+)-ATPase activity was noticed in cervical cancer patients as compared to normal subjects. CONCLUSIONS Increased lipid peroxidation, insufficient antioxidant potential and changes in C/P molar ratio as well as activity of Na(+)K(+)-ATPase cause structural and functional abnormalities in the erythrocytes of cervical cancer patients.

Biochemical changes in tumor tissues of oral cancer patients.

OBJECTIVES Our aim was to assess the oxidative stress in tumor tissues of oral cancer patients by measuring the levels of lipids, thiobarbituric acid reactive substances (TBARS) and antioxidants. DESIGN AND METHODS This study has been conducted on oral tumor tissues of 48 adult male oral cancer patients with various clinical stages (stage II to stage IV; 16 of each) and normal tissues of an equal number of age and sex matched disease free healthy subjects. The levels of lipids, lipid peroxidation and antioxidants in buccal mucosa of healthy subjects and oral cancer patients were assayed using colorimetric methods, except for vitamin E (fluorometriy). RESULTS Total cholesterol and esterified cholesterol were markedly increased whereas phospholipids and free fatty acids were significantly decreased in tumor tissues as compared to normal tissues. The decrease in TBARS levels and functional compromise of antioxidant defense mechanisms were observed in the tumor tissues as compared to normal subjects. CONCLUSIONS The low availability of peroxidizable substrates and the enhanced antioxidant capacity in tumor tissues make them less susceptible to oxidative stress, conferring a selective growth advantage on tumor cells.

Molecular structure, spectroscopic studies and first-order molecular hyperpolarizabilities of ferulic acid by density functional study

Quantum chemical calculations of energies, geometrical structure and vibrational wavenumbers of ferulic acid (FA) (4-hydroxy-3-methoxycinnamic acid) were carried out by using density functional (DFT/B3LYP/BLYP) method with 6-31 G(d,p) as basis set. The optimized geometrical parameters obtained by DFT calculations are in good agreement with single crystal XRD data. The vibrational spectral data obtained from solid phase FT-IR and FT-Raman spectra are assigned based on the results of the theoretical calculations. The observed spectra are found to be in good agreement with calculated values. The electric dipole moment (micro) and the first hyperpolarizability (beta) values of the investigated molecule have been computed using ab initio quantum mechanical calculations. The calculation results also show that the FA molecule might have microscopic nonlinear optical (NLO) behavior with non-zero values. A detailed interpretation of the infrared and Raman spectra of FA was also reported. The energy and oscillator strength calculated by time-dependent density functional theory (TD-DFT) results complements with the experimental findings. The calculated HOMO and LUMO energies shows that charge transfer occur within the molecule. The theoretical FT-IR and FT-Raman spectra for the title molecule have been constructed.

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.

The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer's Disease, Parkinson's Disease, and Huntington's Disease: A Mini Review.

Neurodegenerative diseases affect not only the life quality of aging populations, but also their life spans. All forms of neurodegenerative diseases have a massive impact on the elderly. The major threat of these brain diseases includes progressive loss of memory, Alzheimers disease (AD), impairments in the movement, Parkinsons disease (PD), and the inability to walk, talk, and think, Huntingtons disease (HD). Oxidative stress and mitochondrial dysfunction are highlighted as a central feature of brain degenerative diseases. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, has been known to play a vital role in the pathophysiology of neurodegenerative diseases including AD, PD, and HD. A large number of studies have utilized oxidative stress biomarkers to investigate the severity of these neurodegenerative diseases and medications are available, but these only treat the symptoms. In traditional medicine, a large number of medicinal plants have been used to treat the symptoms of these neurodegenerative diseases. Extensive studies scientifically validated the beneficial effect of natural products against neurodegenerative diseases using suitable animal models. This short review focuses the role of oxidative stress in the pathogenesis of AD, PD, and HD and the protective efficacy of natural products against these diseases.

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.

Anticarcinogenic and antilipidperoxidative effects of Tephrosia purpurea (Linn.) Pers. in 7, 12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinoma

Objectives: To investigate the chemopreventive potential and antilipidperoxidative effects of ethanolic root extract of Tephrosia purpurea (Linn.) Pers. (TpEt) on 7,12-dimethylbenz(a)anthracene (DMBA)- induced hamster buccal pouch carcinoma. Materials and Methods: Oral squamous cell carcinoma was developed in the buccal pouch of Syrian golden hamsters, by painting with 0.5% DMBA in liquid paraffin, thrice a week, for 14 weeks. The tumor incidence, volume and burden were determined. Oral administration of TpEt at a dose of 300 mg/kg, b.w., to DMBA (on alternate days for 14 weeks)- painted animals significantly prevented the incidence, volume and burden of the tumor. Results: TpEt showed potent antilipidperoxidative effect, as well as enhanced the antioxidant status in DMBA- painted animals. Conclusion: TpEt has potent chemopreventive efficacy and significant antilipidperoxidative effect, in DMBA-induced oral carcinogenesis. Further studies are needed to isolate and characterize the bioactive principle.

Ferulic Acid Inhibits 7,12-Dimethylbenz[α]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.

Chemopreventive efficacy of piperine in 7,12-dimethyl benz [a] anthracene (DMBA)-induced hamster buccal pouch carcinogenesis: An FT-IR study

The present study is designed to investigate the effect of piperine in modifying the carcinogenic process, as well as biochemical alterations at the molecular level during DMBA-induced hamster buccal pouch carcinogenesis by FT-IR spectroscopy. Specific changes were noticed in the FT-IR spectral features of DMBA-induced hamster buccal pouch carcinoma. These alterations include structural changes of proteins and possible increase of its content, an increase in the nuclear-to-cytoplasm ratio, an increase in the relative amount of DNA, an enhancement in the phosphorylation of proteins, a loss of hydrogen bonding of the C-OH groups in the amino acid residues of proteins and diminished lipid peroxidation which were accompanied by a significant reduction in the relative amount of lipids compared to untreated control animals. Administration of piperine significantly increased the levels of lipid peroxidation and decreased the levels of proteins and nucleic acid content that were found to increase in oral cancer bearing animals. In conclusion, the results of the present study suggest that piperine may exert its chemopreventive effect by modulating the biochemical changes at the molecular level during DMBA-induced hamster buccal pouch carcinogenesis which can be detected using FT-IR spectroscopic technique.

Antihyperglycemic and antilipidperoxidative effects ofTephrosia purpurea seed extract in streptozotocin induced diabetic rats

The aim of the present study was to evaluate the antihyperglycemic and antilipidperoxidative effects of ethanolic seed extract ofTephrosia purpurea (TpEt) in streptozotocin induced diabetic rats. Hyperglycemia associated with an altered hexokinase and glucose 6 phosphatase activities, elevated lipid peroxidation, disturbed enzymatic and non-enzymatic antioxidants status were observed in streptozotocin induced diabetic rats. Oral administration of “TpEt” at a dose of 300mg/kg bw showed significant antihyperglcemic and antilipidperoxidative effects as well as increased the activities of enzymatic antioxidants and levels of non enzymatic antioxidants. We also noticed that the antihyperglycemic effect of plant drug (TpEt) was comparable to that of the reference drug glibenclamide. Our results clearly indicate that “TpEt” has potent antihyperglycemic and antilipidperoxidative effects in streptozotocin induced diabetic rats and therefore further studies are warranted to isolate and characterize the bioactive antidiabetic principles from “TpEt”.