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1.
Andrologia ; 46(6): 650-8, 2014 Aug.
Article in English | MEDLINE | ID: mdl-23848841

ABSTRACT

Resveratrol has been considered as an antioxidant in biological system. However, its role in male reproductive biology has not yet been evaluated in much detail. Present study analysed its effect on male reproductive function in adult mouse, after its intraperitoneal administration (2, 8 and 20 mg kg b.wt.(-1) per day) for 2 weeks. The generation of reactive oxygen species and lipid peroxidation in testis increased with concomitant decrease in sperm count and motility following resveratrol treatment as compared with the control group. Resveratrol had a negative impact on the activities of antioxidant enzymes namely catalase and superoxide dismutase and on the level of reduced glutathione. Increase in the level of oxidised glutathione by resveratrol lead to a shift in the redox ratio. Additionally, a significant loss of Leydig cells and alterations in testicular histomorphology (excessive vacuolisation and shrinkage of seminiferous tubules) was also observed. In conclusion, the deleterious effects of resveratrol on germ cells could be attributed to its pro-oxidant ability leading to testicular tissue damage.


Subject(s)
Reproduction/drug effects , Stilbenes/toxicity , Animals , Catalase/metabolism , Glutathione/metabolism , Injections, Intraperitoneal , Leydig Cells/drug effects , Leydig Cells/pathology , Lipid Peroxidation/drug effects , Male , Mice , Oxidants/administration & dosage , Oxidants/toxicity , Reactive Oxygen Species/metabolism , Reproduction/physiology , Resveratrol , Seminiferous Tubules/drug effects , Seminiferous Tubules/pathology , Sperm Count , Sperm Motility/drug effects , Stilbenes/administration & dosage , Superoxide Dismutase/metabolism , Testis/drug effects , Testis/pathology , Testis/physiopathology , Wine/analysis
2.
Andrologia ; 45(1): 56-65, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22640552

ABSTRACT

Oxidative stress is a leading cause of male infertility. To combat this, germ cells and spermatozoa are endowed with various enzymes, vitamins and proteins. Certain other components of food, including bioflavonoids, also provide protection against free radicals. This study analysed the effect of quercetin, a bioflavonoid, on male reproductive function in adult mice, after intraperitoneal treatment with varying concentrations of quercetin (2, 8 and 20 mg kg(-1) b.wt.) for 2 weeks. Quercetin increased the generation of reactive oxygen species and lipid peroxidation in the testis with concomitant decrease in sperm count and motility in a dose-dependent manner. Activities of antioxidant enzymes catalase, superoxide dismutase and levels of reduced glutathione were found to be decreased in a dose-dependent manner. Also, the levels of oxidised glutathione were increased leading to a shift in redox ratio. The testicular histomorphology was also altered dose dependently. Germ cell kinetic study revealed significant loss of various germ cell populations with increasing dose of quercetin. Interestingly, there was a reduction in germinal epithelium thickness concomitant with an increase in seminiferous tubule lumen diameter. In conclusion, the deleterious effects of quercetin on germ cells could be attributed to its pro-oxidant ability that might affect the Sertoli cell functions.


Subject(s)
Antioxidants/pharmacology , Quercetin/administration & dosage , Reproduction/drug effects , Animals , Catalase/metabolism , Dose-Response Relationship, Drug , Glutathione/analysis , Lipid Peroxidation/drug effects , Male , Mice , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Sperm Count , Sperm Motility/drug effects , Spermatozoa/drug effects , Superoxide Dismutase/metabolism , Testis/cytology , Testis/drug effects , Testis/metabolism
3.
Fundam Clin Pharmacol ; 25(2): 237-47, 2011 Apr.
Article in English | MEDLINE | ID: mdl-20408879

ABSTRACT

Acute pancreatitis is an inflammatory disease of the pancreas caused by release of activated digestive enzymes in the pancreas. A number of therapeutic options have been explored for acute pancreatitis, but none has been unambiguously proven to be effective. Rosiglitazone has been shown to be efficacious in acute pancreatitis; thus, the present study was planned to evaluate the effect of rosiglitazone on pancreatic regeneration. Pancreatitis was induced by l-arginine in rats which were divided into three groups: cholecystokinin (CCK-8), rosiglitazone and vehicle. Rats were sacrificed at four time points after induction of pancreatitis i.e. 24h, day 3, day 14 and day 28 for determination of biochemical parameters and histological examination. Rate of DNA synthesis, immunohistochemistry and RT-PCR were performed at day 3 and day 7. Drug administration was started 2h after last L-arginine injection and continued till the day of sacrifice. The lower levels of enzyme in rosiglitazone-treated group compared to vehicle group proved the efficacy of rosiglitazone treatment in reducing severity of acute pancreatitis. The nucleic acid content and rate of DNA synthesis were significantly higher in rosiglitazone group indicating promotion of pancreatic regeneration. The histopathological score were lower in rosiglitazone group. Rosiglitazone treatment promoted pancreatic regeneration after acute injury. Currently, only symptomatic treatment is available, regeneration of pancreatic tissue can be a future strategy in the management of acute pancreatitis. Further studies are required to support the findings of the present study.


Subject(s)
PPAR gamma/agonists , Pancreatitis/drug therapy , Regeneration/drug effects , Thiazolidinediones/pharmacology , Acute Disease , Animals , Arginine/toxicity , DNA/biosynthesis , Disease Models, Animal , Female , Male , Pancreatitis/physiopathology , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Rosiglitazone , Severity of Illness Index , Sincalide/pharmacology , Time Factors
4.
Dig Dis Sci ; 56(5): 1369-78, 2011 May.
Article in English | MEDLINE | ID: mdl-21082353

ABSTRACT

BACKGROUND: The exact etiopathology of inflammatory bowel disease is still unclear. Most of the therapies present are directed towards symptomatic improvement. Surgical therapy in the form of restorative proctocolectomy is reserved for the terminal stage disease, which is unresponsive to medical therapy. The present study was conducted to evaluate the effect of green tea in experimentally induced inflammatory bowel disease. METHODS: A total of 36 animals were included in the study. The animals were divided into five groups (n = 6): Group I-Vehicle (ethanol), group II-TNBS + ethanol, group III-green tea-treated group was divided into two sub-groups on the basis of different doses: group IIIA-TNBS + green tea (35 mg/kg), group IIIB-TNBS + green tea (70 mg/kg), group IV-TNBS + sulfasalazine (360 mg/kg), group V-TNBS + sulfasalazine (360 mg/kg) + green tea (least effective dose found in group III). After completion of 2 weeks of treatment, the rats were killed under ether anesthesia by cervical dislocation for assessment of intestinal inflammation, histological analysis, myeloperoxidase assay, malondialdehyde assay, and TNF-α estimation. RESULTS: The study showed that green tea alone and in combination with sulfasalazine reduced inflammatory changes induced by tri nitro benzene sulfonic acid in rats. This reduction is associated with reduced malondialdehyde, lipid peroxidation, and TNF-α. This correlates well with both gross morphological and histopathological scores. CONCLUSIONS: The authors concluded that a combination of green tea extract with sulfasalazine showed greater efficacy than single drug treatment.


Subject(s)
Camellia sinensis/chemistry , Inflammatory Bowel Diseases/chemically induced , Inflammatory Bowel Diseases/drug therapy , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Sulfasalazine/therapeutic use , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Lipid Peroxidation , Male , Malondialdehyde/metabolism , Peroxidase/metabolism , Plant Extracts/administration & dosage , Rats , Rats, Wistar , Sulfasalazine/administration & dosage , Trinitrobenzenesulfonic Acid/toxicity , Tumor Necrosis Factor-alpha
5.
Eur J Med Chem ; 45(11): 4997-5005, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20805013

ABSTRACT

In the present study, an attempt was made to study the acute and sub-acute toxicity profile of G3-COOH Poly (propyl ether imine) [PETIM] dendrimer and its use as a carrier for sustained delivery of model drug ketoprofen. Drug-dendrimer complex was prepared and characterized by FTIR, solubility and in vitro drug release study. PETIM dendrimer was found to have significantly less toxicity in A541 cells compared to Poly amido amine (PAMAM) dendrimer. Further, acute and 28 days sub-acute toxicity measurement in mice showed no mortality, hematological, biochemical or histopathological changes up to 80 mg/kg dose of PETIM dendrimer. The results of study demonstrated that G3-COOH PETIM dendrimer can be used as a safe and efficient vehicle for sustained drug delivery.


Subject(s)
Dendrimers/administration & dosage , Dendrimers/chemistry , Drug Carriers , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Cell Line , Chromatography, High Pressure Liquid , Female , Humans , Ketoprofen/administration & dosage , Male , Mice , Spectrophotometry, Infrared
6.
Eur J Pharmacol ; 628(1-3): 282-9, 2010 Feb 25.
Article in English | MEDLINE | ID: mdl-19958759

ABSTRACT

Current treatment options for acute pancreatitis are supportive and symptomatic. Due to lack of agents targeting the underlying pathophysiology a large amount of experimental work is going on to identify novel therapeutic agents. The present study was carried out to explore if melatonin can modulate the spontaneous regeneration process of the pancreas after experimentally induced acute pancreatitis. Rats were given two i.p. injections of l-arginine in a dose of 200mg/100g at an interval of 1h for induction of pancreatitis. After this rats were randomly divided into three groups i.e. saline, CCK-8 and melatonin. Drug treatment was started 2h after the last l-arginine injection and continued till the day of sacrifice. An additional only saline treated control group was included for comparison. Animals in each group were sacrificed at 24h, days 3, 14 and 28 after pancreatitis induction for determination of biochemical parameters (serum amylase, lipase and IL-10 and pancreatic amylase, total proteins and nucleic acid content) and histological examination. For rate of DNA synthesis and immunohistochemical studies animals were sacrificed at day 3 and day 7. Melatonin treatment was found to be beneficial in acute pancreatitis. Severity of acute pancreatitis was significantly reduced in melatonin group. Nucleic acid content, rate of DNA synthesis, pancreatic proteins and pancreatic amylase content were significantly improved. Histopathological examination showed significantly lower total scores in melatonin group. Results of melatonin group were comparable to that of positive control, CCK-8 group. Thus melatonin treatment was found to promote the spontaneous regeneration process of pancreatic tissue.


Subject(s)
Melatonin/pharmacology , Pancreas/drug effects , Pancreas/physiopathology , Pancreatitis/physiopathology , Regeneration/drug effects , Amylases/blood , Amylases/metabolism , Animals , DNA/biosynthesis , Disease Models, Animal , Female , Gene Expression Regulation/drug effects , Immunohistochemistry , Interleukin-10/blood , Kinetics , Lipase/blood , Male , Nucleic Acids/metabolism , Pancreas/enzymology , Pancreas/metabolism , Pancreatitis/blood , Pancreatitis/enzymology , Pancreatitis/metabolism , Proteins/metabolism , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction
7.
Indian J Exp Biol ; 46(8): 583-90, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18814487

ABSTRACT

Manuka honey (MH, 5g/kg) provided protection against trinitro-benzo-sulphonic acid induced colonic damage. Combination therapy (MH+sulfasalazine) also reduced colonic inflammation and all the biochemical parameters were significant compared to control and MH alone treated group. Combination therapy showed additive effect of the MH which restored lipid peroxidation and improvement of antioxidant parameters. Morphological and histological scores were significantly reduced in combination groups. In inflammatory model of colitis, oral administration of MH (5g/kg) and combination with sulfasalazine (360 mg/kg) with MH (5g/kg) significantly reduced the colonic inflammation. The results indicate the additive effect of Manuka honey with sulfasalazine in colitis.


Subject(s)
Antioxidants/metabolism , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/metabolism , Honey , Sulfasalazine/therapeutic use , Animals , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/pathology , Disease Models, Animal , Male , Rats , Rats, Wistar , Sulfasalazine/pharmacology
8.
Eur Neuropsychopharmacol ; 18(10): 760-7, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18701263

ABSTRACT

BACKGROUND: The mechanism of epileptogenesis is not well established. There is higher incidence of seizures among patients with chronic inflammatory disease. Cytokines are rapidly induced in the brain after a variety of stimuli including inflammation. Aim of this study was to produce various inflammatory models and seizure to understand the role of TNFalpha in above mentioned models. MATERIALS AND METHODS: A total of 54 male rats were included in the study. Animals were divided into 3 groups of colitis, arthritis, and cotton wool granuloma. Each group had 3 subgroups of control, model and treatment. At the end of 3 days in colitis, 17 days in arthritis and 7 days in cotton wool granuloma groups a subconvulsive dose of PTZ (40 mg/kg i.p) was injected to note seizure onset and seizure score. Brain samples were subjected to DNA fragmentation testing. Presence of inflammation was confirmed by morphology and histology. Plasma and brain TNFalpha levels were measured. RESULTS: The models of colitis, arthritis and CWG were effectively produced as evidenced by morphology and histology scores (p<0.001). Seizure onset was reduced and grade was increased (p<0.001). Thalidomide reduced the morphological, histological (p<0.002), DNA fragmentation and seizure grade (p<0.001) while increased seizure onset (p<0.001) in the arthritis group. TNFalpha levels in both plasma and brain were reduced following thalidomide treatment (p<0.002) in arthritis group. There were no significant findings in colitis or cotton wool granuloma groups. CONCLUSION: Inflammation was associated with decreased threshold to PTZ induced seizure. Thalidomide is effective in reducing the extent of arthritis as well as reducing the seizure scoring and increasing seizure onset in the adjuvant arthritis group. Thalidomide was also effective in reducing TNFalpha levels thus contributing to its antiepileptic activity.


Subject(s)
Cytokines/metabolism , Inflammation/metabolism , Seizures/metabolism , Acetic Acid/adverse effects , Analysis of Variance , Animals , Arthritis/chemically induced , Arthritis/drug therapy , Arthritis/metabolism , Colitis/chemically induced , Colitis/drug therapy , Colitis/metabolism , Cyclooxygenase Inhibitors/therapeutic use , DNA Fragmentation/drug effects , Disease Models, Animal , Etoricoxib , Freund's Adjuvant/adverse effects , Immunosuppressive Agents/therapeutic use , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/pathology , Male , Pyridines/therapeutic use , Rats , Rats, Wistar , Seizures/chemically induced , Seizures/drug therapy , Seizures/pathology , Sulfones/therapeutic use , Thalidomide/therapeutic use
9.
Phytother Res ; 22(11): 1511-9, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18688794

ABSTRACT

To evaluate the effect of different doses of Manuka honey in experimentally induced inflammatory bowel disease in rats. Adult Wistar rats of either sex were used (n = 30). Colitis was induced by a single intracolonic administration of TNBS dissolved in 35% ethanol. The rats (n = 30) were divided into five groups (n = 6) and were treated with vehicle (ethanol), TNBS, Manuka honey (5 g/kg, p.o.), Manuka honey (10 g/kg, p.o.) or sulfasalazine (360 mg/kg, p.o.) body weight for 14 days. After completion of treatment, the animals were killed and the following parameters were assessed: morphological score, histological score and different antioxidant parameters.Manuka honey at different doses provided protection against TNBS-induced colonic damage. There was significant protection with Manuka honey 5 g/kg as well as with 10 g/kg body weight compared with the control (p < 0.001). All the treated groups showed reduced colonic inflammation and all the biochemical parameters were significantly reduced compared with the control in the Manuka honey treated groups (p < 0.001). Manuka honey at different doses restored lipid peroxidation as well as improved antioxidant parameters. Morphological and histological scores were significantly reduced in the low dose Manuka honey treated group (p < 0.001). In the inflammatory model of colitis, oral administration of Manuka honey 5 g/kg and Manuka honey 10 g/kg body weight significantly reduced the colonic inflammation. The present study indicates that Manuka honey is efficacious in the TNBS-induced rat colitis model, but these results require further confirmation in human studies.


Subject(s)
Colitis/drug therapy , Colon/drug effects , Honey , Inflammatory Bowel Diseases/drug therapy , Analysis of Variance , Animals , Antioxidants/metabolism , Colitis/chemically induced , Colitis/prevention & control , Colon/metabolism , Colon/pathology , Disease Models, Animal , Glutathione/metabolism , Inflammation/drug therapy , Inflammatory Bowel Diseases/chemically induced , Inflammatory Bowel Diseases/prevention & control , Lipid Peroxidation , Male , Peroxidase/metabolism , Rats , Rats, Wistar , Sulfasalazine/pharmacology , Superoxide Dismutase/metabolism , Trinitrobenzenesulfonic Acid/toxicity
10.
Mol Cell Biochem ; 319(1-2): 133-9, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18642056

ABSTRACT

We investigated the possible mechanisms of All-trans retinoic acid (ATRA)-promoted apoptosis induced by alpha-tocopherol succinate (alpha-TS) in freshly isolated leukemic cells obtained from chronic myeloid leukemic patients. alpha-TS at 50 microM concentration significantly decreased superoxide dismutase (SOD) activity and reduced glutathione (GSH) by 29% and 25%, respectively, and increased lipid peroxidation level by 33%. Though 10 microM ATRA did not affect these parameters, it further significantly enhanced alpha-TS-induced changes. Bax expression in the leukemic cells was increased by treatment with ATRA, alpha-TS, and their combination to 40%, 240%, and 320%, respectively, without any change in Bcl2 and p53 expression. C-myc was down regulated by treatment with ATRA, alpha-TS and their combination to 22%, 48.5%, and 52%, respectively. In conclusion, the data reveal that enhancement of alpha-TS-induced apoptosis by ATRA in leukemic cells was through up regulation of Bax and lipid peroxidation, and down regulation of c-myc and GSH.


Subject(s)
Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Apoptosis/drug effects , Gene Expression Regulation, Leukemic/drug effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Proto-Oncogene Proteins c-myc/biosynthesis , Tretinoin/pharmacology , alpha-Tocopherol/pharmacology , bcl-2-Associated X Protein/biosynthesis , Adult , Antineoplastic Agents/agonists , Drug Synergism , Female , Glutathione/metabolism , Humans , Lipid Peroxidation/drug effects , Male , Middle Aged , Superoxide Dismutase/metabolism , Tretinoin/agonists , Tumor Cells, Cultured , alpha-Tocopherol/agonists
11.
Dis Esophagus ; 21(2): 103-7, 2008.
Article in English | MEDLINE | ID: mdl-18269643

ABSTRACT

The ability of reactive oxygen species to induce cellular damage and to cause cell death opens the possibility of exploiting this property in the treatment of esophageal cancer through a free radical mediated mechanism. The present study was carried out with the aim of evaluating the changes in the antioxidant defense status in esophageal cancer patients treated without and with neoadjuvant therapy (NAT). Forty surgically resected tissue specimens from tumors, tissue adjoining the tumors and paired macroscopically normal mucosa were obtained from esophageal cancer patients treated with or without chemo-radiotherapy. An evaluation of antioxidant defense system in the normal, adjoining and tumor esophageal tissues in response to NAT revealed decreased catalase activity in tumor and adjoining tissues as compared to their respective normal tissue levels. Similarly, decreased superoxide dismutase activity was observed in tumor tissue in response to NAT. In both the treatment groups (with and without NAT), no significant change was observed in the enzyme activity of glutathione reductase in the normal, adjoining and tumor tissues. Enhanced glutathione peroxidase activity was found in tumor tissue, as compared to the adjoining and paired normal tissue of patients after NAT. Estimation of reduced glutathione (GSH) levels showed a significant decline in GSH levels in esophageal tumors after NAT. Depletion of GSH, an endogenous antioxidant, would elevate drug sensitivity and might predispose neoplastic cells to apoptosis in response to NAT. The antioxidant enzymes in the esophageal carcinoma thus may play an important role in influencing the final outcome upon NAT course.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents/therapeutic use , Antioxidants/physiology , Cisplatin/therapeutic use , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/metabolism , Fluorouracil/therapeutic use , Adult , Aged , Female , Humans , Male , Middle Aged
12.
Int J Radiat Oncol Biol Phys ; 70(2): 563-71, 2008 Feb 01.
Article in English | MEDLINE | ID: mdl-18207033

ABSTRACT

PURPOSE: To analyze p53, bcl-2, c-myc, and cyclooxygenase-2 protein expression changes and examine their relationship with various antioxidant enzymes in esophageal carcinoma patients. METHODS AND MATERIALS: Patients in Group 1 underwent transhiatal esophagectomy and those in Group 2 were administered chemoradiotherapy followed by surgery after 4 weeks of neoadjuvant therapy. RESULTS: The relationship analysis among the various protein markers and antioxidant enzymes showed an inverse correlation between bcl-2 and superoxide dismutase/catalase in tumor tissues, irrespective of the treatment arm followed. An important positive association was observed between bcl-2 and reduced glutathione levels in the tumor tissue of patients receiving neoadjuvant therapy. Another apoptosis-modulating marker, c-myc, in the tumor tissue of Group 2 patients showed similar pattern levels (high and low) as that of superoxide dismutase/catalase. The association of cyclooxygenase-2 and p53 with various antioxidant enzymes showed a significant positive correlation between cyclooxygenase-2 expression and catalase activity and an inverse trend between p53 expression and superoxide dismutase and catalase activity in the tumor tissue of patients given neoadjuvant therapy. In addition, patients with overexpressed p53 protein levels had lower glutathione peroxidase enzyme levels and vice versa in the tumor tissue of patients who had undergone surgery as their main mode of treatment. CONCLUSION: The results of this study broaden the insight into the relationships shared among oncoproteins and the antioxidant defense system, and this could be helpful in the clinical management of esophageal carcinoma.


Subject(s)
Antioxidants/metabolism , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/radiotherapy , Proto-Oncogene Proteins/metabolism , Adult , Aged , Catalase/metabolism , Cyclooxygenase 2/metabolism , Esophageal Neoplasms/metabolism , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Prospective Studies , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Statistics, Nonparametric , Superoxide Dismutase/metabolism , Tumor Suppressor Protein p53/metabolism
13.
Brain Cogn ; 67(1): 25-30, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18078701

ABSTRACT

OBJECTIVE: To study the effects of green tea extract administration on age-related cognition in young and old male Wistar rats. METHODS: Young and old rats were orally administered 0.5% green tea extract for a period of eight weeks and were evaluated by passive avoidance, elevated maze plus paradigm and changes in acetylcholinesterase activity. RESULTS: Treatment of young and old rats with the extract resulted in no significant difference in performance on the rota rod treadmill test/righting reflex time. Green tea extract significantly improved learning and memory in older rats, with increased retention latency to enter difference in passive avoidance test. In the elevated maze test, green tea treatment resulted in significantly more number of entries in the enclosed arm by the young and old rats. Decline in acetylcholinesterase activity was observed in the cerebrum of green tea treated old rats in comparison to the green tea treated young rats. CONCLUSION: Green tea extract administration is effective in enhancing learning and memory in aged rats, and hence, may serve useful in reversing age-related deficits.


Subject(s)
Camellia sinensis , Cognition Disorders/prevention & control , Memory Disorders/prevention & control , Phytotherapy , Plant Extracts/pharmacology , Acetylcholinesterase/drug effects , Acetylcholinesterase/metabolism , Administration, Oral , Age Factors , Aging , Analysis of Variance , Animals , Anxiety/prevention & control , Learning/drug effects , Male , Memory/drug effects , Plant Extracts/administration & dosage , Psychomotor Performance/drug effects , Random Allocation , Rats , Rats, Wistar
14.
J Chemother ; 18(1): 74-84, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16572897

ABSTRACT

Esophageal carcinoma has a high incidence in India but its etiology remains unknown. In the present study the correlation between apoptosis regulatory proteins and anti-oxidant enzymes in 40 esophageal carcinoma patients was examined. Patients in one group were operated by transhiatal esophagectomy and in the second group were administered cisplatin (30 mg/m2/day) and 5-fluorouracil (5-FU) (750 mg/m2/day) daily for three days followed by surgery after four weeks of neo-adjuvant therapy (NAT). Complete pathological response was achieved in 15% of patients. Results obtained by Western blot analysis showed over-expressed p53 and COX-2 protein levels in the tumor tissues as compared to the adjoining tissue and its paired normal mucosa in both groups of patients. Immunohistochemical studies showed heterogenous p53 staining pattern with sections showing both nuclear and cytoplasmic staining with 36.8% mild, 10.5% moderate and 52.6% intense p53 immunoreactivity. Both COX-2 and iNOS immunostaining revealed 25% negative and 75% mild to strongly positive immunoreactivity. Correlation studies demonstrated a positive relationship between p53 and COX-2 (P=0.030; r = +0.70) in surgically treated patients. The association of COX-2 and p53 with various anti-oxidant enzymes showed a significantly positive correlation between COX-2 expression and catalase activity and an inverse correlation between p53 expression and superoxide dismutase and catalase activity in the tumor tissue of patients given NAT. In addition, we observed a negative trend between p53 expression levels and GPx enzyme levels in both the adjoining and tumor tissue of patients having undergone surgery as main mode of treatment.


Subject(s)
Adenocarcinoma/enzymology , Catalase/metabolism , Cyclooxygenase 2/metabolism , Esophageal Neoplasms/enzymology , Nitric Oxide Synthase Type II/metabolism , Superoxide Dismutase/metabolism , Tumor Suppressor Protein p53/metabolism , Adenocarcinoma/drug therapy , Adenocarcinoma/surgery , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/metabolism , Blotting, Western , Cisplatin/administration & dosage , Combined Modality Therapy , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/surgery , Esophagectomy , Esophagus/metabolism , Female , Fluorouracil/administration & dosage , Free Radical Scavengers/metabolism , Humans , Male , Middle Aged , Neoadjuvant Therapy
15.
Int J Radiat Biol ; 81(12): 901-10, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16524845

ABSTRACT

PURPOSE: To evaluate the effect of low-dose (<50 cGy) whole body ?-irradiation on the antioxidant defense system in the liver and the lungs of mice at various post-irradiation intervals. MATERIALS AND METHODS: Male Balb/c mice, 5 - 6 weeks of age, were divided into irradiated and non-irradiated groups. Whole body irradiation was done with gamma-rays from a (60)Co source at doses of 10, 25 and 50 cGy (48.78 cGy/min). Lipid peroxidation and antioxidant status were measured in the liver and the lungs at 4, 12 and 24 h after irradiation. RESULTS: Lipid peroxidation increased by 1.38 and 2.0 fold in lung and liver respectively at 12 h after exposure to 25 cGy. Whole body exposure to 25 and 50 cGy significantly (p < 0.05) increased the hepatic reduced glutathione at 4 h. Reduced glutathione continued to rise until 12 h and returned to the basal level at 24 h, whereas in the lungs it remained elevated until 24 h at 10 and 25 cGy. Antioxidant enzymes activities for superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase increased by 1.22, 1.13, 1.22 and 1.11 fold respectively (p < 0.05) in the liver at 4 h after exposure to 50 cGy and remained elevated at almost the same level up to 12 h after exposure. Surprisingly these antioxidant defense enzymes remained unaltered in the lung at the above radiation doses. CONCLUSIONS: Low-dose whole body gamma-irradiation differentially modulates the antioxidant defense system in the liver and lungs of mice. The induction of endogenous glutathione, immediately after exposure to low-dose -irradiation, may be beneficial in protecting the cells from reactive oxygen species (ROS) induced oxidative stress.


Subject(s)
Gamma Rays/adverse effects , Whole-Body Irradiation/adverse effects , Animals , Catalase/metabolism , Dose-Response Relationship, Radiation , Glutathione Peroxidase/metabolism , Glutathione Reductase/metabolism , Lipid Peroxidation , Liver/radiation effects , Lung/radiation effects , Male , Mice , Mice, Inbred BALB C , Superoxide Dismutase/metabolism
17.
Trop Gastroenterol ; 25(4): 156-61, 2004.
Article in English | MEDLINE | ID: mdl-15912972

ABSTRACT

Helicobacter pylori (H. pylori) is the commonest bacterial pathogen found worldwide and more than half the world population aged 40 years and above is colonized with it. The infection rate is >95 % in some African countries. In 1994, the International Agency for Research on cancer classified H. pylori as a class I carcinogen in humans. It causes chronic active gastritis, duodenal and gastric ulcer and gastric malignancy, and is thought to be associated with coronary artery disease, cerebral stroke, vitamin B12 and iron-deficiency anaemia, etc. Therefore, non-invasive test-and-treatment strategies are widely recommended in primary care settings. Conventionally, H. pylori infection can be diagnosed by invasive techniques using an upper gastrointestinal endoscope for obtaining multiple biopsies from different sites of the stomach for RUT, culture, histological examination, polymerase chain reaction (PCR), etc. and by non-invasive tests such as Urea breath test (UBT), stool antigen test and blood serology. At present, 13/14C-UBT is considered the test of choice for confirmation of H. pylori infection. The UBT is based on the principle, that isotopically labelled urea ingested by an H. pylori--infected patient is rapidly hydrolysed by the microbial urease. The released 13/14CO2 is absorbed across the mucous layer to the gastric mucosa and hence, excreted via the systemic circulation in the breath which is collected and measured. The non-hydrolysed urea is excreted completely in the urine within 3-4 days. 13C-UBT being non-radioactive, 13C-UBT can be used in pregnant women and children, and a user's license is not required. There is still no standard protocol accepted and followed internationally for this test. Although the methods are almost similar, various laboratories/clinics use variable tracer doses, test meals, timings and methods for breath collection, and different cut-off values, which make formal validation studies necessary. This review describes the present status of the UBT and its application in the detection of H. pylori infection.


Subject(s)
Breath Tests/methods , Helicobacter Infections/diagnosis , Helicobacter pylori , Urea/metabolism , Humans , Reproducibility of Results
18.
Indian J Biochem Biophys ; 40(6): 416-22, 2003 Dec.
Article in English | MEDLINE | ID: mdl-22900369

ABSTRACT

Stable free radical scavenging and antiperoxidative activities of resveratrol, a component of grapes and red wine, were evaluated and compared with some other known bioflavonoids (quercetin, catechin, kaempferol, myricetin, fisetin, ellagic acid and naringenin) widely present in the plant kingdom. Free radical scavenging activity was measured in an in vitro chemical system (DPPH assay), while for antiperoxidative activity, biological system comprising of hepatic and pulmonary homogenates was employed. Antiradical activity assay showed quercetin and myricetin to be stronger antiradical agents than resveratrol. Structure-activity study revealed that O-dihydroxy group on ring B of flavonoid plays a crucial role. A double bond at 2-3 position conjugated with a 4-oxo function and hydroxy groups at positions 3 and 5 also contribute towards antiradical activity of flavonoids. Resveratrol exhibited stronger antiradical activity than kaempferol and naringenin and was also more efficient than alpha-tocopherol, a known strong endogenous non-flavonoid antioxidant, used for comparison. In vitro antiperoxidative assay showed fisetin as the strongest and kaempferol as the weakest antioxidant. Resveratrol was found to be stronger antioxidant than catechin, myricetin, kaempferol and naringenin, but was weaker than quercetin, fisetin and alpha-tocopherol. Antiradical and antiperoxidative activities of resveratrol may explain its beneficial effects in disease states. Assays exhibited no direct correlation between antiradical and antiperoxidative activities of the phenolics.


Subject(s)
Flavonoids/pharmacology , Free Radical Scavengers/pharmacology , Lipid Peroxidation/drug effects , Stilbenes/pharmacology , Animals , Biphenyl Compounds/chemistry , Flavonoids/chemistry , Free Radical Scavengers/chemistry , Kinetics , Male , Mice , Mice, Inbred BALB C , Phenols/chemistry , Phenols/pharmacology , Picrates/chemistry , Resveratrol , Stilbenes/chemistry
19.
Indian J Exp Biol ; 41(3): 201-4, 2003 Mar.
Article in English | MEDLINE | ID: mdl-15267147

ABSTRACT

Effect of 50Hz sinusoidal electromagnetic field (SEMF) on normal bone physiology was evaluated in young and old female and male Wistar rats. Exposure to SEMF resulted in increased 45Ca retention in tibias of aged animals only. Levels of serum calcium in young female and male rats were significantly less than in respective aged rats. These were further decreased after 4 weeks of SEMF exposure. SEMF exposure did not change the serum calcium levels in aged rats, and inorganic phosphates in young and aged animals. Similarly, the levels of tartrate resistant acid and alkaline phosphatase were significantly decreased in young rats, whereas the levels remained unchanged in aged rats of either sex. The results revealed that SEMF of 1mT can prevent bone calcium loss due to aging in animals.


Subject(s)
Aging/metabolism , Calcium/metabolism , Electromagnetic Fields , Tibia/radiation effects , Animals , Female , Male , Rats , Rats, Wistar , Tibia/metabolism
20.
Indian J Exp Biol ; 40(6): 739-44, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12587722

ABSTRACT

Naturally occurring plant products belonging to different chemical classes namely alizarin, an anthraquinone, caffeine, a methylxanthine derivative and quercetin, a flavonol were studied for their effect on elimination of metabolites of [14C]-N-nitrosodiethylamine (14C-NDEA) through respiration in mice. Treatment with caffeine, quercetin and alizarin at doses of 200, 9 and 9 microg/ml respectively, in drinking water enhanced the exhalation of 14CO2, one of the major end products of NDEA metabolism. Radioactive CO2 exhaled in 60 min increased by 2, 1.61 and 1.4-folds in animals treated with caffeine, quercetin and alizarin for 8 weeks respectively. This increase in exhalation in caffeine-treated animals was achieved even in 2 weeks. These compounds had no adverse effects on the absorption of radioactive NDEA from the gut of the animals as shape and time of 14CO2 peak was similar in i.p. and orally administered [14C-NDEA]. Increased detoxification/elimination of the carcinogen could be one of the mechanisms for the anticarcinogenic properties of these phytochemicals in lung tumorigenesis induced by orally administered NDEA.


Subject(s)
Alkylating Agents/metabolism , Anthraquinones/pharmacology , Caffeine/pharmacology , Carbon Dioxide/metabolism , Carbon Radioisotopes , Central Nervous System Stimulants/pharmacology , Diethylnitrosamine/metabolism , Metabolic Clearance Rate/drug effects , Quercetin/pharmacology , Administration, Oral , Alkylating Agents/administration & dosage , Animals , Diethylnitrosamine/administration & dosage , Digestive System/metabolism , Injections, Intraperitoneal , Mice , Time Factors
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