Namasivayam Nalini

Annamalai University , Annāmalainagar, State of Tamil Nadu, India

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Publications (107)206.94 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Background: Colon cancer is one of the most common cancers in both men and women. The present study is an effort to unravel the anticarcinogenic effects of rosmarinic acid (RA) in 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Administration of DMH induces multiple tumors in the rat colon, which mimics human colon cancer. Methods: Male Wistar rats were divided into six groups and fed a high-fat diet. Group 1 served as control, group 2 rats were given RA [5 mg/kg body weight (b.w.)] orally every day for a total period of 30 weeks, and groups 3-6 were given weekly injections of DMH (20 mg/kg b.w. subcutaneous) once a week in the groin for the first 15 weeks. In addition to DMH, groups 4-6 received RA at a dose of 5 mg/kg b.w. during the initiation and postinitiation stages, and also throughout the entire study period. Colon tissues were examined histologically; further, the extent of oxidative stress was assessed by measuring lipid peroxidation and antioxidant levels in the colonic mucosa of rats. Results: Macroscopic and microscopic tumors were identified in all the groups that received DMH. The results revealed that supplementation with RA significantly inhibited the tumor formation and tumor multiplicity in DMH-treated rats. RA supplementation to DMH-administered rats significantly reduced the cell proliferation markers, namely, argyrophilic nucleolar organizing regions as well as proliferative cell nuclear antigen labeling index. In addition, RA supplementation reduces the expressions of tumor necrosis factor-α, interlukin-6, and cyclooxygenase-2, and modulates the expression of p65. Conclusions: The above findings clearly underline the chemopreventive efficacy of RA against DMH-induced colon carcinogenesis.
    Journal of basic and clinical physiology and pharmacology 09/2014;
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    ABSTRACT: Zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butane], one of the active phenolic components isolated from Zingiber officinale, has antioxidant and anticarcinogenic properties. In our study, we have evaluated the effect of different doses of zingerone on lipid peroxidation (thiobarbituric acid-reactive substances, lipid hydroxyl radical and conjugated dienes), tissue enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase), and nonenzymatic antioxidants (reduced glutathione, vitamin E, vitamin C), and also the formation of aberrant crypt foci (ACF) in male albino Wistar rats with colon cancer induced using 1,2-dimethylhydrazine (DMH). The rats were divided into six groups. Group 1 served as a control group and received a modified pellet diet; the rats in group 2 received a modified pellet diet along with zingerone (40 mg/kg b.w., orally every day); groups 3-6 were administered DMH (20 mg/kg b.w., subcutaneously) once a week for the first 4 weeks; and groups 4-6 received zingerone at three different doses of 10, 20 and 40 mg/kg b.w., respectively, every day for 16 weeks. Increased tumour incidence and ACF formation were accompanied by a decrease in the tissue lipid peroxidation, enzymatic and nonenzymatic antioxidant activities observed in the colon of DMH-treated rats. Supplementation with zingerone in DMH-treated rats led to a significant decrease in the tumour incidence and ACF formation with simultaneous modulation in the level of tissue lipid peroxidation and antioxidant status. Thus, in conclusion, we can suggest that zingerone effectively inhibits DMH-induced colon carcinogenesis in male Wistar rats.
    European Journal of Cancer Prevention 09/2014; 23(5):361-371. · 2.97 Impact Factor
  • N Sangeetha, N Nalini
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    ABSTRACT: To authenticate the colon cancer preventive potential of silibinin, the efficacy of silibinin needs to be tested by evaluating an organ-specific biomarker. The aim of this study was to evaluate the impact of silibinin on the colonic expression of the caudal-type homeobox transcription factor (CDX2) an intestine specific tumor suppressor gene and its downstream targets in the colon of rats challenged with 1,2 dimethyl hydrazine (DMH). Rats of groups 1 and 2 were treated as control and silibinin control. Rats under groups 3 and 4 were given DMH (20 mg/kg body weight (b.w.) subcutaneously) once a week for 15 consecutive weeks from the 4th week of the experimental period. In addition, group 4 rats alone were treated with silibinin (50 mg/kg b.w. per os) everyday throughout the study period of 32 weeks. Histological investigation and messenger RNA and protein expression studies were performed in the colonic tissues of experimental rats. Findings of the study revealed that DMH administration significantly decreased the expression of CDX2 and Guanylyl cyclase C (GCC) in the colon of experimental rats. Further the decreased levels of CDX2 protein, colonic mucin content, and increased number of mast cells in the colon of DMH alone-administered rats reflects the onset of carcinogenesis. The pathological changes caused due to CDX2 suppression were attenuated by silibinin supplementation.
    Human & Experimental Toxicology 04/2014; · 1.31 Impact Factor
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    ABSTRACT: Colon cancer is the third most global oncologic problem faced by medical fraternity. Troxerutin, a flavonoid present in tea, coffee, cereal grains, and a variety of fruits and vegetables, exhibits various pharmacological and biological activities. This study was carried out to investigate the effect of troxerutin on xenobiotic metabolizing enzymes, colonic bacterial enzymes and the development of aberrant crypt foci (ACF) during 1,2-dimethylhydrazine (DMH) induced experimental rat colon carcinogenesis. Male albino Wistar rats were randomly divided into six groups. Group 1 served as control. Group 2 received troxerutin (50 mg/kg b.w., p.o. every day) for 16 weeks. Groups 3-6 received subcutaneous injections of DMH (20 mg/kg b.w.) once a week, for the first four weeks. In addition, groups 4-6 received different doses of troxerutin (12.5, 25, 50 mg/kg b.w., p.o. every day respectively) along with DMH injections. Our results reveal that DMH treated rats exhibited elevated activities of phase I enzymes such as cytochrome P450, cytochrome b5, cytochrome P4502E1, NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase and reduced activities of phase II enzymes such as glutathione-S-transferase (GST), DT-diaphorase (DTD) and uridine diphospho glucuronyl transferase (UDPGT) in the liver and colonic mucosa of control and experimental rats. Furthermore, the activities of fecal and colonic mucosal bacterial enzymes, such as β-glucronidase, β-glucosidase, β-galactosidase and mucinase were found to be significantly higher in DMH alone treated rats than those of the control rats. On supplementation with troxerutin to DMH treated rats, the alterations in the activities of the biotransforming enzymes, bacterial enzymes and the pathological changes were significantly reversed, the effect being more pronounced when troxerutin was supplemented at the dose of 25 mg/kg b.w. Thus troxerutin could be considered as a good chemopreventive agent against the formation of preneoplastic lesions in a rat model of colon carcinogenesis.
    Experimental and Molecular Pathology 02/2014; 96(1):15-26.. · 2.13 Impact Factor
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    ABSTRACT: The present study was aimed to investigate the chemopreventive potential of troxerutin on 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the antioxidant and lipid peroxidation (LPO) status. Rats were randomly divided into six groups. Group I rats served as control. Group II rats received troxerutin (50 mg/kgb.w., p.o.) for 16 weeks. Groups III-VI rats received subcutaneous injections of DMH (20 mg/kgb.w., s.c.) once a week, for the first 4 weeks. In addition to DMH, groups IV-VI rats received troxerutin at the doses of 12.5, 25 and 50 mg/kgb.w., respectively. In DMH treated rats, our results showed decreased activities of antioxidants and increased levels of LPO in the liver. Moreover, LPO and antioxidants in the colon were found to be significantly diminished in DMH the treated rats. Furthermore, enhanced activity of colonic vitamin C and vitamin E levels were observed in DMH alone treated rats (group III), which was significantly reversed on troxerutin supplementation. Troxerutin at the dose of 25 mg/kgb.w. had shown profound beneficial effects by exhibiting near normal biochemical profile and well-preserved colon histology as compared to the other two tested doses (12.5 and 50 mg/kgb.w.). These findings suggest that troxerutin could serve as a novel agent for colon cancer chemoprevention.
    Environmental Toxicology and Pharmacology 01/2014; 37(1):174-184. · 2.01 Impact Factor
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    ABSTRACT: OBJECTIVES: The present study has aimed to evaluate chemopreventive potential of d-carvone on oxidative stress markers, biotransforming enzymes, incidence of colonic polyps and aberrant crypt foci (ACF) in 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis. MATERIALS AND METHODS: Rats were randomly divided into six groups, with group I serving as control. Group II animals received d-carvone every day orally (20 mg/kg body weight) for 16 weeks; groups III-VI received subcutaneous injections of DMH (20 mg/kg body weight) once a week, for the first 4 weeks. In addition, groups IV-VI received different doses of d-carvone (5, 10 and 20 mg/kg body weight everyday orally) along with DMH injections. RESULTS: Our results revealed that supplementation with d-carvone significantly reduced incidence of polyps/ACF and ACF multiplicity in DMH-exposed rats compared to DMH-alone-exposed rats. Moreover, our results showed reduced activities of liver and circulatory antioxidants and increased levels of lipid peroxidation by products in DMH-exposed animals, which were significantly reversed on supplementation with d-carvone. In addition, colonic antioxidants and lipid peroxidation were significantly diminished in DMH-exposed rats, which were significantly elevated on supplementation with d-carvone. Furthermore, we also determined activities of biotransforming enzymes, which were found to be altered in DMH-exposed rats, but reversed on d-carvone supplementation. All these observations of changes were supported by histochemical findings. CONCLUSION: Overall, results obtained from this study suggest that d-carvone at 10 mg/kg body weight provided optimum protection and could be used as an effective chemopreventive agent against colon carcinogenesis induced by DMH.
    Cell Proliferation 12/2013; 46(6):705-720. · 2.27 Impact Factor
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    ABSTRACT: The present study was aimed to investigate the chemopreventive potential of troxerutin on 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the antioxidant and lipid peroxidation (LPO) status. Rats were randomly divided into six groups. Group I rats served as control. Group II rats received troxerutin (50mg/kgb.w., p.o.) for 16 weeks. Groups III-VI rats received subcutaneous injections of DMH (20mg/kgb.w., s.c.) once a week, for the first 4 weeks. In addition to DMH, groups IV-VI rats received troxerutin at the doses of 12.5, 25 and 50mg/kgb.w., respectively. In DMH treated rats, our results showed decreased activities of antioxidants and increased levels of LPO in the liver. Moreover, LPO and antioxidants in the colon were found to be significantly diminished in DMH the treated rats. Furthermore, enhanced activity of colonic vitamin C and vitamin E levels were observed in DMH alone treated rats (group III), which was significantly reversed on troxerutin supplementation. Troxerutin at the dose of 25mg/kgb.w. had shown profound beneficial effects by exhibiting near normal biochemical profile and well-preserved colon histology as compared to the other two tested doses (12.5 and 50mg/kgb.w.). These findings suggest that troxerutin could serve as a novel agent for colon cancer chemoprevention.
    Environmental toxicology and pharmacology. 12/2013; 37(1):174-184.
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    ABSTRACT: The present study has aimed to evaluate chemopreventive potential of d-carvone on oxidative stress markers, biotransforming enzymes, incidence of colonic polyps and aberrant crypt foci (ACF) in 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis. Rats were randomly divided into six groups, with group I serving as control. Group II animals received d-carvone every day orally (20 mg/kg body weight) for 16 weeks; groups III-VI received subcutaneous injections of DMH (20 mg/kg body weight) once a week, for the first 4 weeks. In addition, groups IV-VI received different doses of d-carvone (5, 10 and 20 mg/kg body weight everyday orally) along with DMH injections. Our results revealed that supplementation with d-carvone significantly reduced incidence of polyps/ACF and ACF multiplicity in DMH-exposed rats compared to DMH-alone-exposed rats. Moreover, our results showed reduced activities of liver and circulatory antioxidants and increased levels of lipid peroxidation by products in DMH-exposed animals, which were significantly reversed on supplementation with d-carvone. In addition, colonic antioxidants and lipid peroxidation were significantly diminished in DMH-exposed rats, which were significantly elevated on supplementation with d-carvone. Furthermore, we also determined activities of biotransforming enzymes, which were found to be altered in DMH-exposed rats, but reversed on d-carvone supplementation. All these observations of changes were supported by histochemical findings. Overall, results obtained from this study suggest that d-carvone at 10 mg/kg body weight provided optimum protection and could be used as an effective chemopreventive agent against colon carcinogenesis induced by DMH.
    Cell Proliferation 09/2013; · 2.27 Impact Factor
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    ABSTRACT: Zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butane], one of the active phenolic components isolated from Zingiber officinale, has antioxidant and anticarcinogenic properties. In our study, we have evaluated the effect of different doses of zingerone on lipid peroxidation (thiobarbituric acid-reactive substances, lipid hydroxyl radical and conjugated dienes), tissue enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase), and nonenzymatic antioxidants (reduced glutathione, vitamin E, vitamin C), and also the formation of aberrant crypt foci (ACF) in male albino Wistar rats with colon cancer induced using 1,2-dimethylhydrazine (DMH). The rats were divided into six groups. Group 1 served as a control group and received a modified pellet diet; the rats in group 2 received a modified pellet diet along with zingerone (40 mg/kg b.w., orally every day); groups 3-6 were administered DMH (20 mg/kg b.w., subcutaneously) once a week for the first 4 weeks; and groups 4-6 received zingerone at three different doses of 10, 20 and 40 mg/kg b.w., respectively, every day for 16 weeks. Increased tumour incidence and ACF formation were accompanied by a decrease in the tissue lipid peroxidation, enzymatic and nonenzymatic antioxidant activities observed in the colon of DMH-treated rats. Supplementation with zingerone in DMH-treated rats led to a significant decrease in the tumour incidence and ACF formation with simultaneous modulation in the level of tissue lipid peroxidation and antioxidant status. Thus, in conclusion, we can suggest that zingerone effectively inhibits DMH-induced colon carcinogenesis in male Wistar rats.
    European Journal of Cancer Prevention 07/2013; · 2.97 Impact Factor
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    ABSTRACT: Colorectal cancer is one of the leading causes of cancer related deaths in Western countries and is becoming increasingly common in Asia. Rosmarinic acid (RA), one of the major components of polyphenol possesses attractive remedial features. The purpose of this study is to investigate the possible chemopreventive mechanism of action of RA against 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the circulatory antioxidant status and colonic bacterial enzymes activities. Additionally, we analyzed the aberrant crypt foci (ACF) formation and multiplicity in the colon of experimental groups. Wistar male rats were divided into six groups. Group 1 was control rats, group 2 rats received RA (10 mg/kg b.w., p.o. everyday), rats in groups 3-6 received DMH (20 mg/kg b.w., s.c.) for the first 4 weeks. In addition to DMH, groups 4-6 received 2.5, 5, and 10 mg/kg b.w. RA respectively. The results revealed that supplementation with RA significantly reduced the formation of ACF and ACF multiplicity in DMH treated rats. Moreover RA supplementation prevented the alterations in circulatory antioxidant enzymes and colonic bacterial enzymes activities. Overall, our results showed that all three doses of RA inhibited carcinogenesis, though the effect of the intermediary dose of 5 mg/kg b.w. was more pronounced.
    Environmental Toxicology and Pharmacology 11/2012; 34(3):949-958. · 2.01 Impact Factor
  • Selvaraj Aranganathan, Namasivayam Nalini
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    ABSTRACT: Cancer is the second leading cause of death worldwide and is increasing at an alarming rate. The present study was to evaluate the antiproliferative effcts of hesperetin, a flavonoid commonly found in many herbal medicines and foods, on aberrant crypt foci (ACF), argyrophylic nucleolar organizer regions (AgNORs) and proliferating cell nuclear antigen (PCNA) in 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats. Rats were given subcutaneous injections of DMH (20 mg/kg body weight) weekly for 15 weeks to induce carcinogenesis, and hesperetin was administered orally at the dose of 20 mg/kg body weight. DMH exposure alone produced a high incidence of ACF and showed positive staining for PCNA and AgNORs in colonic tissues. Supplementation with hesperetin lowered the PCNA labeling index and suppressed the formation of ACF in the rats with colon cancer. These results clearly reveal that dietary hesperetin possesses antiproliferative ability against chemically induced colon tumourigenesis. Copyright © 2012 John Wiley & Sons, Ltd.
    Phytotherapy Research 08/2012; · 2.40 Impact Factor
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    ABSTRACT: Colorectal cancer is one of the leading causes of cancer related deaths in Western countries and is becoming increasingly common in Asia. Rosmarinic acid (RA), one of the major components of polyphenol possesses attractive remedial features. The purpose of this study is to investigate the possible chemopreventive mechanism of action of RA against 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the circulatory antioxidant status and colonic bacterial enzymes activities. Additionally, we analyzed the aberrant crypt foci (ACF) formation and multiplicity in the colon of experimental groups. Wistar male rats were divided into six groups. Group 1 was control rats, group 2 rats received RA (10mg/kg b.w., p.o. everyday), rats in groups 3-6 received DMH (20mg/kg b.w., s.c.) for the first 4 weeks. In addition to DMH, groups 4-6 received 2.5, 5, and 10mg/kg b.w. RA respectively. The results revealed that supplementation with RA significantly reduced the formation of ACF and ACF multiplicity in DMH treated rats. Moreover RA supplementation prevented the alterations in circulatory antioxidant enzymes and colonic bacterial enzymes activities. Overall, our results showed that all three doses of RA inhibited carcinogenesis, though the effect of the intermediary dose of 5mg/kg b.w. was more pronounced.
    Environmental toxicology and pharmacology. 08/2012;
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    ABSTRACT: Colorectal carcinogenesis is one of the most common cancers/lethal diseases. Chronic inflammation is considered a risk factor for colorectal cancer. Hesperetin, a flavonone found in citrus fruits and oranges is shown to possess potent growth inhibitory effects against various human cancer cells. It possesses anti-inflammatory and antioxidant properties. AIM OF THE SCOPE: In the present study, we have evaluated the chemopreventive efficacy of hesperetin against rat colon carcinogenesis in male Wistar rats. Group 1 served as control, received modified pellet diet and group 2 rats received 20 mg/kg body weight of hesperetin p.o. every day. Groups 3-6 rats were given subcutaneous injections of 1,2-dimethylhydrazine (DMH, 20 mg/kg body weight) once a week for 15 consecutive weeks. In addition, rats in group 4 received hesperetin as in group 2 for the first 15 weeks (initiation), group 5 rats received hesperetin as in group 2 after the last injection of DMH and continued till the end of the experimental period (postinitiation). Group 6 rats received hesperetin as in group 2 throughout the entire experimental period of 32 weeks. Detection of cell proliferation markers such as proliferating cell nuclear antigen (PCNA) (immunohistochemistry), argyrophilic nucleolar organizer regions (AgNORs) (silver staining); apoptosis (immunoblotting and immunohistochemistry); angiogenic growth factors (ELISA) indicated decreased cell proliferation and increased apoptotic markers in the colon. In addition, decreased angiogenic growth factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and downregulation of mRNA Cyclooxygenase-2 (COX-2) expressions were observed in mucosal and fecal samples of hesperetin-supplemented rats. Hesperetin supplementation showed an inhibition of cell proliferation markers, angiogenic growth factors, COX-2 mRNA expression and induction of apoptosis. Thus, hesperetin can be used as a potent chemopreventive agent against DMH-induced colon cancer.
    Toxicology mechanisms and methods 03/2012; 22(5):397-408. · 1.37 Impact Factor
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    ABSTRACT: Colon cancer is one of the serious health problems in most developed countries and its incidence rate is increasing in India. Hesperetin (HN) (3',5,7-trihydroxy-4'-methoxyflavonone) and hesperetin analogue (HA) were tested for their apoptosis inducing ability. Methyl thiazolyl tetrazolium assay revealed a dose as well as duration-dependent reduction of HT-29 (colon adenocarcinoma) cellular growth in response to HN and HA treatment. At 24 h 70 μM of HN and 32 μM of HA showed 50% reduction of HT-29 cellular growth. Acridine orange/ethidium bromide staining showed apoptotic features of cell death induced by HN and HA. Rhodamine 123 staining showed significant reduction in mitochondrial membrane potential induced by HN and HA. HN and HA induced DNA damage was confirmed by comet tail formation. Lipid peroxidation markers (TBARS) and protein oxidation marker (PCC) were significantly elevated in HN and HA treated groups. Enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were slightly decreased in their activities compared to control (untreated HT-29 cells). Results of Western blot analysis of apoptosis associated genes revealed an increase in cytochrome C, Bax, cleaved caspase-3 expression and a decrease in Bcl-2 expression. These findings indicate that HN and HA induce apoptosis on HT-29 via Bax dependent mitochondrial pathway involving oxidant/antioxidant imbalance.
    Food and Chemical Toxicology 03/2012; 50(3-4):660-671. · 3.01 Impact Factor
  • JAYARAMAN JAYACHITRA, NAMASIVAYAM NALINI
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    ABSTRACT: Our aim was to investigate the effect of naringenin on hyperlipidemia induced by ethanol. Groups 1 and 2 rats received isocaloric glucose and 0.5% carboxymethyl cellulose (CMC); groups 3 and 4 received 20% (6 g/kg body weight p.o.) ethanol everyday for 60 days. Groups 2 and 4 rats received naringenin (50 mg/kg body weight/day in 0.5% CMC) everyday during the last 30 days of the experiment. There were increased levels of plasma total cholesterol (TC), triglycerides (TG), free fatty acids (FFA), very low density lipoproteins (VLDL), low density lipoproteins (LDL) and tissue TC, TG, FFA, HMG CoA reductase and alterations in collagen content of ethanol‐fed rats, which on naringenin supplementation showed decreased levels of plasma and tissue TC, TG and FFA, HMG CoA reductase and collagen content. There was a significant decrease in the levels of plasma high density lipoprotein (HDL), lipoprotein lipase (LPL) and lecithin cholesterol acyltransferase (LCAT) of ethanol‐fed rats, which on naringenin supplementation showed an increase in the levels of HDL and LPL with ethanol alone–fed rats. Naringenin can efficiently prevent the accumulation of plasma lipids and lipoproteins. PRACTICAL APPLICATIONSAlcohol abuse, alcohol intolerance, alcohol dependence and other alcohol related disabilities are some of the most challenging public health problems. A phytotherapeutic approach in the new drug development can provide many valuable drugs from traditional plant sources. The use of herbal medicines for the treatment of hepatotoxicity has gained importance throughout the world. Renewed attention to alternative medicine and natural therapies has stimulated new wave of research interest in traditional practice, and there is a need to look for more potent agents with lesser side effects. The present study is aimed to identify the efficacy of naringenin by uncovering its underlying mechanism of action against alcohol‐induced liver disease for effective therapy. Naringenin, an important flavonoid, is widely present in fruits and vegetables. Naringenin is known to possess a number of significant beneficial properties. If the biochemical and histological findings are positive, indicating the marked hepatoprotective efficacy of naringenin, it could be subjected to human trials in the future.
    Journal of Food Biochemistry 01/2012; 36(4). · 0.76 Impact Factor
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    ABSTRACT: Colon cancer is one of the serious health problems in most developed countries and its incidence rate is increasing in India. Hesperetin (HN) (3',5,7-trihydroxy-4'-methoxyflavonone) and hesperetin analogue (HA) were tested for their apoptosis inducing ability. Methyl thiazolyl tetrazolium assay revealed a dose as well as duration-dependent reduction of HT-29 (colon adenocarcinoma) cellular growth in response to HN and HA treatment. At 24 h 70 μM of HN and 32 μM of HA showed 50% reduction of HT-29 cellular growth. Acridine orange/ethidium bromide staining showed apoptotic features of cell death induced by HN and HA. Rhodamine 123 staining showed significant reduction in mitochondrial membrane potential induced by HN and HA. HN and HA induced DNA damage was confirmed by comet tail formation. Lipid peroxidation markers (TBARS) and protein oxidation marker (PCC) were significantly elevated in HN and HA treated groups. Enzymic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were slightly decreased in their activities compared to control (untreated HT-29 cells). Results of Western blot analysis of apoptosis associated genes revealed an increase in cytochrome C, Bax, cleaved caspase-3 expression and a decrease in Bcl-2 expression. These findings indicate that HN and HA induce apoptosis on HT-29 via Bax dependent mitochondrial pathway involving oxidant/antioxidant imbalance.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 11/2011; 50(3-4):660-71. · 2.99 Impact Factor
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    ABSTRACT: Our findings reported so far demonstrate that silibinin modulates gut microbial enzymes, colonic oxidative stress and Wnt/β-catenin signaling, to exert its antiproliferative effect against 1,2 di-methylhydrazine (DMH) induced colon carcinogenesis. Since xenobiotic metabolizing enzymes play a crucial role in carcinogen activation and metabolism, we aimed to explore the effect of silibinin on xenobiotic metabolizing enzymes during DMH induced colon carcinogenesis. Male albino rats were randomly divided into six groups. Group 1 served as control and group 2 rats received 50mg/kg body weight of silibinin p.o. every day. Groups 3-6 rats were given DMH at a dose of (20mg/kg body weight subcutaneously) once a week for 15 weeks to induce colonic tumors. In addition to DMH, group 4 (initiation), group 5 (post-initiation) and group 6 (entire period) rats received silibinin (50mg/kg body weight, p.o., everyday) at different time points during the experimental period of 32 weeks. Rats exposed to DMH alone showed increased activities of phase I enzymes (cytochrome b5, cytochrome b5 reductase, cytochromeP450, cytochromeP450 reductase, cytochromP4502E1) and decreased activities of phase II enzymes (Uridine diphospho glucuronyl transferase, Glutathione-S-transferase and DT-Diaphorase) in the liver and colonic mucosa as compared to control rats. Silibinin supplementation modulates the xenobiotic metabolizing enzymes favoring carcinogen detoxification. Evaluation of lipid peroxidation and antioxidants status showed that silibinin supplementation counteracts DMH induced hepatic and circulatory oxidative stress. Tumor burden in experimental animals was assessed both macroscopically and microscopically in the colon tissues. Our findings emphasize the potential chemopreventive action of silibinin against DMH induced colon carcinogenesis.
    European journal of pharmacology 11/2011; 674(2-3):430-8. · 2.59 Impact Factor
  • Madhavan Shenbagam, Namasivayam Nalini
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    ABSTRACT: The present study was designed to investigate the effect of rutin on ethanol-induced hepatotoxicity in a dose-dependent manner in rats. Male albino rats were divided into six groups. Group 1 rats served as control and group 2 rats received rutin 100 mg/kg body weight. Hepatotoxicity was induced in groups 3-6 rats (20% ethanol) for 60 days. In addition, groups 4-6 rats received rutin at doses of 25, 50, 100 mg/kg body weight, respectively for the last 30 days of the experiment. We observed a significant increase in the activities of liver marker enzymes, serum amino transferases, alkaline phosphatase, γ-glutamyl transpeptidase the levels of thiobarbituric acid reactive substances, conjugated dienes, lipid hydroperoxides, and a decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione and its related enzymes, vitamins C and E when compared to ethanol-fed rats. Rutin supplementation along with ethanol significantly decreased the levels of liver marker enzymes, lipid peroxidation and significantly elevated the activities of liver SOD, CAT, GSH, glutathione peroxidase, vitamins C and E when compared to untreated ethanol supplemented rats. Among the three doses, 100 mg/kg body weight of rutin was found to exert a more pronounced hepatoprotective effect against ethanol-induced toxicity. Our results were also confirmed by the histopathologic observations.
    Fundamental and Clinical Pharmacology 08/2011; 25(4):493-502. · 1.99 Impact Factor
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    ABSTRACT: Colon cancer risk may be influenced by phase I and II xenobiotic-metabolizing enzyme systems. The chemopreventive agent gallic acid (GA), a plant polyphenol, is found in various natural products. Our aim was to evaluate the potential role of GA on drug-metabolizing enzymes in 1,2-dimethyl hydrazine (DMH) induced rat colon carcinogenesis. The total experimental duration was 30 weeks. The effect of GA (50 mg/kg b.w.) on the activities of phase I enzymes (cytochrome P450 and cytochrome b5) and phase II enzymes (glutathione S-transferase, DT-diaphorase and gamma glutamyl transpeptidase) were assessed in the liver and colonic mucosa and the colons were also examined visually. In DMH induced rats, there was a decrease in the activities of phase II enzymes and an increase in the activities of phase I enzymes. On GA supplementation, there was a significant increase in the activities of phase II enzymes and a significant decrease in the activities of phase I enzymes, in addition to the decreased tumor incidence. Histopathological changes also confirm this. Thus, the marked potential of GA in modulating the phase I and II xenobiotic-metabolizing enzymes suggests that GA may have a major impact on colon cancer chemoprevention.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 04/2011; 49(4):887-92. · 2.99 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is one of the most common etiologies of chronic liver disease worldwide. The pathogenesis of metabolic syndrome associated with NAFLD is still under debate. AIM OF THE SCOPE: This study has investigated the hepatic biochemical and histological changes and also insulin resistance in metabolic syndrome associated with NAFLD. Young male Wistar rats fed a high-fat diet (HFD 42.2% beef tallow) together with N ( ω )-nitro-L-arginine methyl ester (L-NAME; 80 mg/L in drinking water) for 8 weeks and subsequently with 2% d-limonene for the final 4 weeks. HFD-fed rats treated with L-NAME showed increased systolic blood pressure, heart rate, fasting blood glucose, plasma insulin, hepatic marker enzymes, hepatic lipids, circulatory lipid peroxidation by-products, and hepatic phase I enzyme activities with decreased circulatory nonenzymic antioxidant concentrations and hepatic phase II enzyme activities. Dietary supplementation with d-limonene reversed the HFD and L-NAME-induced changes and restored pathological alteration of liver and pancreas. These data provide new insights into the therapeutic approach of d-limonene against the development of the metabolic syndrome associated with NAFLD.
    European Journal of Nutrition 03/2011; 51(1):57-68. · 3.13 Impact Factor