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Biomedical subjects

K L Khanduja

Publications and source records attributed to K L Khanduja.

At least 19 recordsLinked to original sources
PubMed2006

P53, COX-2, iNOS protein expression changes and their relationship with anti-oxidant enzymes in surgically and multi-modality treated esophageal carcinoma patients.

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.

Adenocarcinoma↗
PubMed2005

Low dose gamma-irradiation differentially modulates antioxidant defense in liver and lungs of Balb/c mice.

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.

Animals↗
PubMed2003

Sinusoidal electromagnetic field of 50 hz helps in retaining calcium in tibias of aged rats.

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.

Aging↗
PubMed2002

Caffeine, quercetin and alizarin stimulate the exhalation of metabolic products of [14C]-N-nitrosodiethylamine in mice.

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.

Administration, Oral↗
PubMed2001

Impairment of human sperm motility and viability by quercetin is independent of lipid peroxidation.

Human sperm motility, viability and lipid peroxidation were assessed in Ringer-Tyrode supplemented with different concentrations of quercetin. An irreversible and dose-dependent fall in sperm motility was observed with quercetin (5-200 microm). However, sperm viability was decreased only at higher concentrations (50-100 microm) of quercetin. This inhibition in sperm motility and viability has been linked with decreased Ca2+-ATPase activity, as there was no effect of quercetin on sperm lipid peroxidation.

Calcium-Transporting ATPases↗
PubMed2000

Further observations and characterization of monoclonal antibodies reacting with B cell alloantigens associated with rheumatic fever and rheumatic heart disease.

Elevated levels of B lymphocytes with a unique surface alloantigen have been reported to be characteristic of patients with acute rheumatic fever or rheumatic heart disease. Mouse monoclonal antibodies (mAbs) to this alloantigen have been proposed as being useful in identifying individuals at risk for the development of these sequelae of group A streptococcal infection. However, previous studies have suggested that the discriminating ability of the mAbs was highest when the mAbs were made by using lymphocytes from the same ethnic population. To confirm and extend this observation, additional mouse mAbs were developed and their properties defined. These three mAbs-PG-12A, PG-13A, and PG-20A-reacted with B cells from more than 90% of North Indian patients with acute rheumatic fever or rheumatic heart disease. Each of these three new mAbs identified the highest levels of reactive B cells in patients with active acute rheumatic fever. Lower levels of positive reacting lymphocytes were found in individuals with quiescent chronic rheumatic heart disease, and markedly reduced percentages of reactive cells were observed in normal control subjects. The proportion of reactive lymphocytes in individual patients varied according to which of the three was tested, suggesting the possibility of a spectrum of "rheumatic" epitopes in susceptible individuals. The data further suggested that enhanced discriminatory ability for identifying "at-risk" susceptible patients could be obtained by testing with a combination of mAbs. If reduction in the incidence of acute rheumatic fever can be facilitated by early identification of susceptible individuals, accurate and sensitive detection of a marker antigen would result in more cost-effective public health measures. Additional population studies are required to more precisely define and confirm these detection techniques.

Adult↗
PubMed2000

Status of vitamin E and reduced glutathione in semen of oligozoospermic and azoospermic patients.

AIM: To investigate the status of seminal plasma reduced glutathione (GSH) and vitamin E in three different conditions of spermatogenesis: azoospermia, oligozoospermia and normospermia. METHODS: Reduced glutathione was measured in the seminal plasma by the method of Moron et al (1979), and vitamin E estimation was performed by the method of Taylor et al (1976). RESULTS: Vitamin E levels in seminal plasma of oligospermic and azoospermic samples were significantly decreased to 65.54% and 66.04% respectively as compared to the normospermic group. Levels of reduced glutathione were also significantly decreased in oligospermic and azoospermic group, and the reduction in azoospermic group (76.73%) was more pronounced than oligozoospermic group (62.07%). CONCLUSION: The decrease in reduced glutathione, an endogenous antioxidant, levels in azoospermic and oligozoospermic conditions may cause disruption in the membrane integrity of spermatozoa as a consequence of increased oxidative stress.

Glutathione↗
PubMed1999

Effect of 50 Hz sinusoidal electromagnetic field on the kinetics of 14CO2 exhalation after [14C]-N-nitrosodiethylamine administration in mice.

N-Nitrosodiethylamine (NDEA) has been identified as a typical environmental carcinogen. Its metabolism was studied in mice under the influence of an electromagnetic field (EMF). After intraperitoneal administration of [14C]-NDEA, 0.2 microCi/100 g body weight resulted in 22.8% of the total radioactivity exhaled as 14CO2 within 1 h. Mice were exposed to a 50 Hz, 2 mT (rms) electromagnetic field, 8 h/day for 8 weeks. There was a significant increase in the metabolic turnover of [14C]-NDEA into 14CO2 at the end of both 6 and 8 weeks of field exposure, i.e., 26.9% and 37.4% respectively. The enhanced capacity of mice to metabolize NDEA after the exposure to EMF may result in animals with a smaller amount of the bioactive carcinogen burden, thereby indicating a protective role of 2 mT EMF in a whole animal study.

Animals↗
PubMed1999

Prevention of N-nitrosodiethylamine-induced lung tumorigenesis by ellagic acid and quercetin in mice.

The polyphenolic antioxidants, consumed as an integral part of vegetables, fruits and beverages, are suggested as possessing anticarcinogenic properties. In the present study we have looked into the anticarcinogenic potential of plant polyphenols ellagic acid (EA) and quercetin against N-nitrosodiethylamine-induced lung tumorigenesis in mice. Ellagic acid was able to significantly reduce tumour incidence to 20% from the control value of 72.2%. Similarly, tumour burden was also decreased, although not significantly, from 3.15 to 2.5. Quercetin (QR) caused the tumour incidence to decrease from 76.4% to 44.4% when fed until the third dose of carcinogen. Both of the polyphenols suppressed the tumour incidence mainly by acting at the initiation phase of the carcinogenesis, since continuing the feeding of polyphenols until the termination of the experiment did not cause any apparent change in tumour incidence or tumour burden. Besides this, ellagic acid was found to be a better chemopreventor than quercetin. In order to search for their mechanism of action, the effect of feeding of these compounds on reduced glutathione (GSH), an important endogenous antioxidant, and on lipid peroxidation was investigated. Both ellagic acid and QR caused a significant increase in GSH and decrease in NADPH- and ascorbate-dependent lipid peroxidation. Ellagic acid was found to be more effective in decreasing the lipid peroxidation and increasing the GSH. This may be one of the reasons for its observed better anticarcinogenic property as compared to quercetin.

Animals↗
PubMed1999

Plant polyphenols inhibit benzoyl peroxide-induced superoxide anion radical production and diacylglyceride formation in murine peritoneal macrophages.

Naturally occurring plant polyphenols, which include ellagic acid (EA), tannic acid (TA), caffeic acid (CA), and ferulic acid (FA), were tested for their superoxide anion radical (SOR)-scavenging activities. SOR were produced by interaction of the tumor promoter benzoyl peroxide (BPO) with murine peritoneal macrophages in vitro. The levels of SOR were assessed microscopically by counting the number of formazan-positive cells per 250 cells produced by the reduction of nitro blue tetrazolium. BPO at a concentration of 15 micrograms/1.85 x 10(6) cells/0.5 ml induced maximum formation of SOR in resident and thioglycollate-elicited cells. All the tested polyphenols were able to inhibit the formation of SOR induced by the tumor promoter to a variable degree. Inhibition of BPO-induced SOR formation by polyphenols was in the following order: FA > TA > CA > EA. BPO stimulated the accumulation of diacylglycerol (DAG) in resident and elicited macrophages with concurrent release of choline equivalents from macrophages. Polyphenols inhibited DAG accumulation, which paralleled the inhibition of choline equivalent release. FA was observed to be the most effective and EA the least effective inhibitor of SOR formation, DAG accumulation, and release of choline equivalents. It is likely that inhibition of SOR formation might be due to some interference in the cellular lipid metabolism and phospholipid equivalent deacylation and choline release.

Animals↗
PubMed1999

Vitamin E suppresses the induction of reactive oxygen species release by lipopolysaccharide, interleukin-1beta and tumor necrosis factor-alpha in rat alveolar macrophages.

Over the last decade, although investigations have suggested that vitamin E affects the immune response, not much is known about its affect on the alveolar macrophage functions. In the present study, we have investigated the effect of high vitamin E (DL-alpha-tocopheryl acetate, alpha-TA) supplementation for 10 d on the activation state of rat alveolar macrophages induced by lipopolysaccharide (LPS), interleukin (IL)-1beta or tumor necrosis factor (TNF)-alpha on the basis of their ability to produce reactive oxygen species (ROS), such as superoxide (O2-*) and H2O2. LPS treatment (1 and 10 microg/mL) caused 2.44 and 2.54-fold increases in O2-*, and 2.1 and 2.3-fold increases in H2O2, respectively, from alveolar macrophages (AMs) in the diet group fed 50 mg alpha-TA/kg. However, this enhancement was not observed for the AMs of the diet groups fed 250 or 1,250 mg alpha-TA/kg. Similar results were obtained on treating the AMs with proinflammatory cytokines IL-1beta or TNF-alpha. The observed suppression in ROS release in response to various stimulants may be due to the direct and/or indirect effect of high vitamin E (250 and 1,250 mg alpha-TA/kg diet) supplementation. It may therefore, be concluded that high alpha-TA supplementation in the diet modulates the activation of AMs in rats.

Animals↗
PubMed1998

Ethnic differences in expression of susceptibility marker(s) in rheumatic fever/rheumatic heart disease patients.

The ability of monoclonal antibodies (MAb) against a human B lymphocyte alloantigen has been suggested to discriminate between rheumatic fever "susceptible" individuals and persons with a lower risk of developing RF. However, while such MAb have been reported to identify a majority of RF/RHD patients in some populations, a reduced discriminatory ability has been observed in others. Antigenic variation in the RF marker(s) may exist among ethnic groups which reduce the discriminatory ability of these monoclonal antibodies. We developed MAb using B lymphocytes from RF patients of North Indian ethnic origin. In this same population we compared the new MAb (PGI/MN II) with a previously described MAb of Caucasian ethnic origin (D8/17). In three groups: acute rheumatic fever patients (no evidence of previous attacks of rheumatic fever), patients with chronic rheumatic heart disease and normal controls from the same population, we found a greater discriminating ability of PGI/MNII MAb to identify Indian RF/RHD patients than with the D8/17 MAb. Further, sixty percent of 142 siblings of the RF/RHD patients were "positive" when tested with PGI/MN II. The data from these studies suggest that before such MAb can be used for identification of RF "susceptibles" in public health programs, variation among ethnic populations must be assessed.

Adolescent↗
PubMed1998

Polyphenols inhibit promotional phase of tumorigenesis: relevance of superoxide radicals.

Ellagic acid (EA), tannic acid (TA), caffeic acid (CA), and ferulic acid (FA) offer considerable promise as anticarcinogens. The role of these dietary polyphenols was investigated in the promotional phase of carcinogenesis. Topical application of polyphenols simultaneously with phorbol-12-myristate-13-acetate (PMA) or mezerein resulted in significant protection against 7,12-dimethyl-benz[a]anthracene-induced skin tumors in mice. Caffeic acid was the most effective inhibitor of tumor promotion. In vivo and in vitro treatment of murine peritoneal macrophages with the tumor promoters resulted in stimulation of superoxide anion radical formation. Tannic acid, caffeic acid, and ferulic acid were stronger inhibitors of PMA- and mezerein-induced superoxide anion radical than ellagic acid in in vivo and in vitro conditions. Treatment of [1(3)-14C]glycerol- or [methyl-14C]choline chloride-labeled resident or thioglycollate-elicited macrophages with PMA and mezerein led to accumulation of radioactive diacylglycerol equivalents. The polyphenols were capable of inhibiting these releases.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Changes in rat alveolar macrophageal antioxidant defense and reactive oxygen species release by high dietary vitamin E.

For the past decade there has been emphasis on the immunomodulatory effects of vitamin E apart from its established role as a free radical scavenger. In alveolar macrophages (AMs), the role of vitamin E supplementation has not yet been investigated sufficiently. In the present study we have evaluated the effects of high vitamin E (DL-alpha-tocopheryl acetate, alpha-TA) supplementation for 10 d on rat-alveolar macrophageal antioxidant defense and reactive oxygen species (ROS) release. There was an increase in plasma vitamin E content from 5.22 +/- 1.30, at 50 mg to 12.23 +/- 1.06 and 22.32 +/- 2.02 micrograms/mL at 250 and 1,250 mg alpha-TA/kg dietary supplementation. Alveolar macrophage-vitamin E content enhanced by 56 to 75% at 250 and 1,250 mg alpha-TA diet as compared with control diet. Superoxide dismutase activity decreased and catalase and glutathione peroxidase activities increased significantly in AMs of 250 and 1,250 mg alpha-TA diet-fed rats. Reduced glutathione, total glutathione, and glutathione-S-transferase activity in AMs did not change significantly at any of the high doses of alpha-TA supplementation. On stimulation of AMs by phorbol-12-myristate-13-acetate (PMA), there was 2.8- and 3.5-fold enhancement in superoxide (O2-.) and H2O2 production, respectively, at 50 mg alpha-TA dose. But this increase by PMA could not take place in AMs from animals supplemented with 250 and 1,250 mg alpha-TA. It may therefore be concluded that high alpha-TA supplementation in diet may equip the AMs with a stronger defense against oxygen-free radical mediated damage to them.

Albuminuria↗
PubMed1998

Geriforte stimulates antioxidant defense system.

Geriforte, a herbomineral preparation, feeding at 1 g% dose level for 4 weeks significantly increased catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in liver of mice. In rats, in addition to these enzymes, the levels of reduced glutathione (GSH) were also significantly enhanced. However, only SOD in mice and, CAT and SOD activities in rat lung were significantly elevated after Geriforte treatment. A decrease in superoxide (O2-) and H2O2 release by alveolar macrophages obtained from rats fed on Geriforte containing diet was observed. The results suggest that Geriforte feeding stimulates antioxidant defense system and indicate the future preventive/therapeutic prospects of this preparation against free radical damage under various pathological states.

Animals↗
PubMed1997

Reactive oxygen species formation in peripheral blood neutrophils in different types of smokers.

The present study was envisaged to assess the state of oxidative metabolism of neutrophils, recovered from smokers (cigarette, beedi, hookah and mixed products) and non-smokers. Superoxide anion (O2.-) production was significantly higher in neutrophils from all groups of smokers (P < 0.001). Total leukocyte count (TLC) was significantly more in symptomatic subjects among the cigarette, hookah and mixed smokers (P < 0.05). Total neutrophil count (TNC) was significantly higher in symptomatic than asymptomatic subjects of hookah and mixed smoking groups (P < 0.05). In the pathogenesis of chronic obstructive pulmonary disease (COPD) in tobacco smokers, the role of leukocytosis, increased neutrophil sequestration into the lung, increased neutrophil toxic oxygen species including superoxide release in the lung may cause direct injury to lung tissues.

Adult↗