Biomedical subjects

M P Bansal

Publications and source records attributed to M P Bansal.

At least 19 recordsLinked to original sources

PubMed2006

Inhibition of CDC2/Cyclin B1 in response to selenium-induced oxidative stress during spermatogenesis: potential role of Cdc25c and p21.

Various cell cycle regulators control and coordinate the process of cell cycle. Because of the crucial involvement of CDC2, Cyclin B1, Cdc25c, and p21 in cell cycle regulation, the present study was aimed to investigate the possibility that selenium (Se)-induced oxidative stress mediated alterations in Cdc25c and p21 may cause modulations in the CDC2/Cyclin B1 complex responsible for G2/M phase checkpoint during meiosis I of spermatogenesis. To create different Se status-deficient, adequate and excess Se, male Balb/c mice were fed yeast based Se deficient diet (group I) and deficient diet supplemented with Se as sodium selenite at 0.2 and 1 ppm Se (group II and III) for a period of 8 weeks. After completion of the diet feeding schedule, a significant decrease in the Se and glutathione peroxidase levels were observed in the Se deficient group (I), whereas Se excess group (III) demonstrated an increase in Se levels. Increased levels of lipid peroxidation (LPO) were seen in both group I and group III when compared to group II, thus indicating oxidative stressed conditions. The mRNA and protein expression of CDC2, Cyclin B1, and Cdc25c were found to be significantly decreased in groups I and III. However, the expression of p21, a kinase inhibitor, was found to be elevated in Se deficient and Se excess fed groups. A statistically significant decrease in the CDC2 kinase activity was also seen in the Se deficient and excess groups. These findings suggest that under the influence of Se-induced oxidative stress, the down regulation of CDC2/Cyclin B1 complex is mediated through changes in Cdc25c and p21 leading to the cell cycle arrest and thus providing new dimensions to the molecular mechanisms underlying male infertility.

Animals↗

PubMed2006

Alterations in selenium status influences reproductive potential of male mice by modulation of transcription factor NFkappaB.

Selenium (Se), an essential dietary trace element, is required for the maintenance of male fertility. In order to study its role in spermatogenesis, Balb/c mice with different Se status (Se deficient, group I; adequate, group II and excess, group III) were generated by feeding yeast based Se deficient diet for group I and deficient diet supplemented with Se as sodium selenite at adequate (0.2 ppm) and excess (1 ppm) for group II and III, respectively, for a period of 4 and 8 weeks. Percentage fertility was reduced in group I and III as compared to group II. A significant decrease in Se levels and glutathione peroxidase (GSH-Px) activity were observed in group I animals, whereas increase in GSH-Px activity was seen in group III. Further, significant increase in lipid peroxidation was observed in both Se deficient and excess groups. This indicated that dietary manipulation of Se levels either deficiency or excess leads to increased oxidative stress. Nuclear factor kappa B (NFkappaB), a well-known redox regulated transcription factor has also been suggested to play a crucial role in spermatogenesis. The expression of both p65 and p50 genes (components of NFkappaB) increased in Se deficient group I mice while the expression of the inhibitory IkappaBalpha declined significantly. This indicated activation of NFkappaB in Se deficiency. We also studied iNOS expression, which is a known target gene of NFkappaB, by RT-PCR. Significant elevation in the iNOS levels as well as NO levels was recorded. Both enhanced NO levels and NFkappaB are harmful in the progression of normal spermatogenic cycle. Therefore, present result clearly demonstrates the effect of reduced supply of Se on up-regulation and activation of NFkappaB in testis and its influence on spermatogenesis.

Animals↗

PubMed2005

Role of selenium in regulation of spermatogenesis: involvement of activator protein 1.

Selenium (Se) is involved in the process of male reproduction. Several studies have been carried out to find the mechanism of Se action through identified selenoproteins. Especially selenoenzyme phospholipid glutathione peroxidase (PHGPx, GPx-4) plays a pivotal role in regulating spermatogenesis. However, the action of selenium is best known as an antioxidant which acts through various selenoproteins viz. glutathione peroxidase, thioredoxin reductase and selenoprotein P. Oxidative stress is currently being considered a leading cause of male infertility. Presently, the involvement of redox active transcription factor, AP1 (Activator protein1) in testicular function was studied. AP1 is redox sensitive and also controls cell proliferation. The effects of Se might be mediated through it. Different Se status - deficient, adequate and excess Se - were generated in male Balb/c mice by feeding yeast based selenium deficient diet and deficient diet supplemented with Se as sodium selenite (0.2 and 1 ppm Se), respectively, for a period of 4 and 8 weeks. Se status was checked by measuring the Se levels and glutathione peroxidase (GSH-Px) activity in testis and liver. The reproductive potential of mice was affected at these changed Se levels. Changes in the activity of superoxide dismutase (SOD), levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were observed indicating increased oxidative stress at both the levels. Further, changes in the mRNA expression of GSH-Px, gamma-glutamylcysteine synthetase gammaGCS) and Mn superoxide dismutase (MnSOD) were observed. Decrease in cjun and cfos mRNA levels were observed at both the Se status (deficient and excess) which might be responsible for decreased germ cell number, differentiation and reduced fertility observed at the altered Se levels.

Animals↗

PubMed2005

Effect of cholesterol and 7-beta hydroxycholesterol on glutathione status and nitric oxide production in murine peritoneal macrophages.

Present study was conducted to observe the effect of cholesterol and oxidized cholesterol (7beta-hydroxycholesterol,7beta-OH) on the nitric oxide (NO) production and the redox ratio by lipopolysaccharide-stimulated macrophages. Dose-dependent decrease in NO levels was seen with both cholesterol and 7beta-OH at different incubation intervals (6,12,18,24 hr) and concentrations (2.5,5,7.5microg/ml). On comparison, a significant decrease in the NO was observed at 24 hr interval in 7beta-OH exposed cells with all respective concentrations of cholesterol. Incubation with 7beta-OH also resulted in significant increase in levels of oxidized glutathione (GSSG) and decrease in reduced glutathione (GSH), while cholesterol showed no effect on GSSG levels. Moreover, GSH levels were lowered only at highest concentration (7.5microg/ml), and at longer incubation intervals (18,24 hr) with cholesterol exposure. This altered the redox status in both cholesterol/7beta-OH treated macrophages. Increased redox ratio and decreased NO levels indicated increased oxidative stress and decreased vasodilation by 7beta-OH compared to cholesterol.

Animals↗

PubMed2005

Selenium, a versatile trace element: current research implications.

Selenium (Se), a trace element, has evolved from its toxic properties to an essential element. Se was known a potent antioxidant through glutathione peroxidase (selenium being part of this molecule). Later, many other selenium-binding proteins were discovered and their functions were tried to be known with unsuccessful results in many cases. Se is known to be involved in carcinogenesis, immune function, male reproduction, cardiovascular diseases etc. The specific mechanism of the involvement of the element is still not known. Recent research with application of modern research tools viz. bioinformatics, cDNA microarray and transgenesis have revealed the mechanism of selenium involvement in various processes. This review highlights mysterious and useful roles of selenium in biological processes.

Animals↗

PubMed2004

Reproductive potential of male Portan rats exposed to various levels of lead with regard to zinc status.

The present study was designed to elucidate the mechanisms accounting for disruption of the normal function of the testis exposed to various levels of Pb. Three different doses of Pb (10, 50, 200 mg Pb/kg body weight per d) were given orally to male Portan rats (groups 2, 3, 4). Zn (1 mg Zn/kg body weight per d) was also given with Pb (50 mg Pb/kg body weight per d) in group 5. Treatments continued for 3 months. Plasma luteinizing hormone and follicle-stimulating hormone concentrations were found to be decreased in Pb-exposed rats. This was in turn reflected in the appreciable decline in fertility status. In cell kinetic studies, significant declines in various cell populations (preleptotene, pachytene, young (step 7) spermatids and mature (step 19) spermatids) were seen. However, in group 5 after Zn supplementation, hormone levels, cell numbers and fertility status were found to be close to normal. It is concluded that Pb might act at maturation level to cause conspicuous degenerative changes in the testis; Zn supplementation protected against these effects.

Animals↗

PubMed2004

Effect of selenium-induced oxidative stress on the oxidation reduction system and reproductive ability of male mice.

The present study was carried out to evaluate the effect of selenium (Se)-induced oxidative stress on the oxidation reduction system and the fertility status of male mice. Different levels of Se, a potent antioxidant, were fed in three separate groups for 8 wk to create the different oxidative stress in mice. A significant decrease in the glutathione peroxidase (GSH-Px) in both liver and testis was observed in the Se-deficient (0.02 ppm) group I, whereas enzyme levels in the Se-excess (1 ppm) group were comparable to the Se-adequate (0.2 ppm) group. Glutathione-S-transferase activity was enhanced in group I in comparison to group II; however, no change was seen in group III. The glutathione reductase and superoxide dismutase activities were decreased in the Se-deficient group, whereas the enzyme levels were significantly increased in the Se-excess group. The fertility status of the animals studied in terms of percentage fertility and litter size showed a significant decrease in the reproductive ability of male mice in group I when compared to group II. No changes in the fertility status of animals were observed in group III. Thus, the data clearly indicate the effect of oxidative stress generated by feeding various Se levels on the oxidation reduction system and, consequently, its effect on the reproductive ability of male mice.

Animals↗

PubMed2004

Effect of selenium depletion and supplementation on the kinetics of type I 5'-iodothyronine deiodinase and T3/T4 in rats.

Presently, the effect of selenium (Se) deficiency and excess of Se (1 ppm) on the activity of selenoenzymes type 1 5'-iodothyronine deiodinase (5'-DI), glutathione peroxidase (GSH-Px), and level of thyroid hormones (T3 and T4) was studied in rats. Se levels in the serum and liver, T3 and T4 in the serum, GSH-Px levels in the liver, and 5'-DI activity in the liver/aorta/thyroid were estimated after 1, 2, and 3 mo of Se-deficient (0.02 ppm), Se-adequate (0.2 ppm), and Se-excess (1 ppm) diet feeding. All of these parameters decreased significantly in the Se-deficient group as compared to the adequate group. Within the deficient group, as the Se deficiency progressed, all of the parameters except 5'-DI decreased after 2 and 3 mo in comparison to 1-mo data. Thyroidal 5'-DI activity in Se deficiency showed the maximum increase. A significant increase was observed in all of the above parameters in the 1 ppm Se-supplemented diet group when compared with the adequate Se group; also, as the Se deposition increased within the Se-excess diet group, a significant increase was observed in all of the above parameters. However, as observed by others, the intake of excess of Se (i.e., 2 ppm in the diet) did not elevate the activities of selenoenzymes and thyroid hormones; rather, it had adverse effects. The present study concludes that Se supplementation at least up to 1 ppm enhances the selenoenzyme activities, and above this level, it may not be considered as an indicator of selenoenzyme activities.

Animals↗

PubMed2004

Influence of selenium induced oxidative stress on spermatogenesis and lactate dehydrogenase-X in mice testis.

AIM: To evaluate the effect of oxidative stress on the spermatogenesis and lactate dehydrogenase-X (LDH-X) activity in mouse testis. METHODS: For creating different levels of oxidative stress in mice, three selenium (Se) level diets were fed in separate groups for 8 weeks. Group 1 animals were fed yeast-based Se-deficient (0.02 ppm) diet. Group 2 and Group 3 animals were fed with the same diet supplemented with 0.2 ppm and 1 ppm Se as sodium selenite, respectively. After 8 weeks, biochemical and histopathological observations of the testis were carried out. LDH-X levels in the testis were analyzed by western immunoblot and ELISA. RESULTS: A significant decrease in testis Se level was observed in Group 1 animals, whereas it was enhanced in Group 3 as compared to Group 2. The glutathione peroxidase (GSH-Px) activity was significantly reduced in both the liver and testis in Group 1, but not in Group 2 and 3. A significant increase in the testis glutathione-S-transferase (GST) activity was observed in Group 1, whereas no significant change was seen in Groups 2 and 3. Histological analysis of testis revealed a normal structure in Group 2. A significant decrease in the germ cell population in Group 1 was observed as compared to Group 2 with the spermatids and mature sperm affected the most. Decrease in the lumen size was also observed. In the Se-excess group (Group 3), displacement of germ cell population was observed. Further, a decrease in the LDH-X level in testis was observed in Group 1. CONCLUSION: Excessive oxidative stress in the Se deficient group, as indicated by changes in the GSH-Px/GST activity, affects the spermatogenic process with a reduction in mature sperm and in turn the LDH-X level.

Animals↗

PubMed2002

Antigenic relationships within the genus Salmonella as revealed by anti-Salmonella enteritidis monoclonal antibodies.

A panel of 38 monoclonal antibodies (MAbs) that react with outer membrane proteins (OMPs) of Salmonella enteritidis was produced. On the basis of their binding pattern in ELISA, the MAbs were divided into three groups. The first group, consisting of 15 MAbs, was found to be Salmonella-specific as they did not cross-react with Escherichia coli or Pasteurella multocida. The second group of 15 MAbs cross-reacted with E. coli but not with P. multocida, reflecting the closer antigenic relationship of E. coli with Salmonella. The third group of 8 MAbs cross-reacted with both E. coli and P. multocida, indicating that the antigenic determinants identified by these MAbs are conserved in all the three genera. The antigenic relationship of the Salmonella serovars (S. enteritidis, S. gallinarum, S. typhimurium, S. dublin, S. agona, S. indiana and S. choleraesuis) was studied using OMPs prepared from them and the anti-S. enteritidis MAbs. Three MAbs appeared to be specific for S. enteritidis as they did not cross-react with any of the other Salmonella serovars. Twelve of the 38 MAbs cross-reacted with all the serovars tested. Six of these were specific to the Salmonella genus as they did not cross-react with any of the other Gram-negative bacteria tested. The reactivity pattern of the other MAbs indicated that S. gallinarum was antigenically close to S. enteritidis, followed in order by S. dublin, S. agona, S. typhimurium and S. indiana, whereas S. choleraesuis seemed to be antigenically quite distant from S. enteritidis.

Animals↗

PubMed2002

Growth characteristics and selenium status changes of yeast cells with inorganic and organic selenium supplementation: selenium, a chemopreventive agent.

We attempted to determine the level and form of selenium (Se) that yielded the maximum Se status of yeast cells, for their evaluation as a source of Se for chemopreventive action. The influence of various Se concentrations from organic (selenomethionine) and inorganic (sodium selenite) Se compounds on growth pattern and cell viability and the alterations in the antioxidant enzyme system of yeast were evaluated. A continuous decrease in cell and colony-forming units counts was observed with increasing concentrations of Se from either source. Increasing Se status of yeast cells was found with increasing concentrations of Se with both forms, with much greater uptake for organic Se at maximum Se concentrations. A continuous increase in glutathione peroxidase (GSH-Px) activity with increasing Se concentrations in both forms revealed an active Se response in terms of antioxidant activity, with a more pronounced percentage increase with selenomethionine. A highly significant increase in total glutathione was observed with selenomethionine supplementation, compared with sodium selenite. A decreasing trend in reduced glutathione was observed with increasing organic or inorganic Se concentrations. An increasing trend in glutathione-S-transferase activity was observed with increasing Se concentrations for both forms. Significantly higher values of glutathione-S-transferase were associated with the organic form at higher Se concentrations. There was normal activity of Se in mammalian cells. The results showed that an organic Se source more greatly enhances the Se status of yeast cells and hence could help in chemoprevention if consumed by the population.

Antioxidants↗

PubMed2002

Studies of apoptosis and bcl-2 in experimental atherosclerosis in rabbit and influence of selenium supplementation.

Apoptosis is a ubiquitous physiological mechanism of cell death regulating tissue mass and architecture. An attempt was made in the present study to see the occurrence of apoptotic cell death in three different treatment groups of rabbits viz. Control, HFD fed and HFD + Selenium fed. Apoptotic activity as checked by in situ DNA end labelling (TUNEL Assay) revealed excessive staining, mostly concentrated in plaque region both in fibrous as well as atheromatous plaque in HFD fed animals. However, in selenium (Se) supplemented animals, very little TUNEL staining could be seen, and even that confined to endothelial cells only. The control group on the other hand was totally devoid of any staining. Transmission Electron Microscopic (TEM) study also depicted the occurrence of apoptosis in aortic cells of HFD fed animals and very little in Se supplemented animals. Apoptotic activity has been discussed in relation to oxidative stress in HFD fed group. bcl-2, though an antiapoptotic oncoprotein, was found to be expressed more in atherogenic group as compared to control/HFD + Se treatment. On the whole, the study highlighted the occurrence of apoptotic process in atherosclerosis and the role of Se, a potent antioxidant, in inhibition of apoptotic process in HFD fed animals.

Animals↗

PubMed2001

Effect of alpha-tocopherol on pulmonary antioxidant defence system and lipid peroxidation in cigarette smoke inhaling mice.

BACKGROUND: Free radicals generated in biological systems by cigarette smoke (CS) inhalation can cause oxidative stress in tissues, resulting in lipid peroxidation (LPO). In view of the antioxidant properties of alpha-tocopherol (AT), in the present study, effects of AT on antioxidant defence system and LPO were investigated in mice inhaling CS for different time intervals. RESULTS: Male Balb/c mice were fed orally with AT (5 I.U./Kg.b.wt.) and /or exposed to CS for 2, 4, 6 or 8 weeks. No effect was observed on body growth, diet consumption, water intake and lung weight due to AT and /or CS treatment in any of the groups as compared to their control counterparts. After two weeks of treatment, no change in LPO, reduced glutathione (GSH) levels and antioxidant enzymes were observed except for glutathione reductase (GR) which increased in all the treated groups. A significant increase in pulmonary LPO levels was observed in mice exposed to CS inhalation for 4, 6 or 8 weeks. There was a gradual increase in the LPO levels as the extent of CS inhalation increased from 4 to 8 weeks. However, the extent of increase in LPO levels due to CS exposure for 4, 6 or 8 weeks in the mice treated with AT was comparatively less. A significant decrease in the GSH levels was also observed in all the animals exposed to CS for 4, 6 or 8 weeks. There was a significant increase in the activities of catalase, glutathione peroxidase (GSH-Px) and GR observed in all the groups exposed to CS for 4,6 or 8 weeks. The increase in above antioxidant enzymes seems to be insufficient to combat the oxidative stress posed by CS inhalation. There was a marked decrease observed in the LPO levels in the animals treated with AT alone for 4, 6, or 8 weeks, when compared to their control counterparts. However, the supplementation of AT for 4, 6 or 8 weeks demonstrated a significant increase in GSH levels. CONCLUSION: It appears from our studies that AT exhibits its antioxidant role either directly by scavenging the oxidative species or indirectly by modulating the GSH levels.

Animals↗

PubMed2001

Effect of 7beta-hydroxycholesterol on cellular redox status and heat shock protein 70 expression in macrophages.

The proatherogenic effects of oxidized low-density lipoproteins are attributed to oxysterols, particularly 7beta-hydroxycholesterol. In the present study, we have examined the effect of 7beta-hydroxycholesterol on cellular redox status and heat shock protein 70 (hsp70) expression. Murine peritoneal macrophages were incubated for 24 hours with increasing concentrations of 7beta-hydroxycholesterol (0-25 microg/ml). Intracellular reduced glutathione levels decreased and oxidized glutathione levels increased, thus increasing the redox ratio. Hsp70 expression in macrophages decreased in a dose-dependent fashion. It is suggested that 7beta-hydroxycholesterol exerts oxidative stress on macrophages and makes them more susceptible to its proatherogenic effects by impairing the cellular defense system consisting of antioxidants and stress proteins.

Animals↗

PubMed2001

In vivo and in vitro influence of selenium on DNA/RNA synthesis in spleen and lymphocytes in culture--possible mediation of changes in GSH/GSSG ratio.

Effect of superanutritional levels of selenium (Se) as sodium selenite (0.5 and 1.5 ppm) given orally to Balb/c mice for one and two weeks was observed on the rate of DNA/RNA synthesis, levels of reduced as well as oxidized glutathione (GSH and GSSG) and glutathione peroxidase (GSH-Px)/glutathione-S-transferase (GSH-S-transferase) activities in spleen. Similar effect of three different concentrations of Se (10(-7), 10(-5) and 10(-3) M) in culture media was also observed on the rate of DNA/RNA synthesis in proliferating lymphocytes taken from mice spleen. The results of the present study indicated that with increasing concentration and duration of Se treatment in vivo and in vitro, a marked inhibition of the rate of DNA/RNA synthesis was observed. Levels of total glutathione and GSSG in spleen were elevated significantly only after two weeks in 1.5 ppm treatments. Glutathione peroxidase activities in spleen decreased (p < 0.05) in 1.5 ppm group at one week and in 0.5 ppm group at two week treatment. At higher Se treatment, the activity recovered towards control. However, GSH-S-transferase in spleen remained unchanged at all treatment intervals. The results indicated that changes in glutathione system by increasing Se concentration might account for inhibition of rate of DNA/RNA synthesis.

Animals↗

PubMed2001

Influence of 7beta-hydroxycholesterol on glutathione status and nitric oxide production in macrophages: in vitro studies.

Incubation of murine peritoneal macrophages with 7beta-hydroxycholesterol (7beta-OH) for 24 hr led to dose-dependent reduction in cellular glutathione content as well as nitrite levels in the medium. Treatment with an inorganic form of selenium, sodium selenite which is a potent antioxidant, elevated the cellular glutathione levels and decreased nitrite levels. Our results suggest that 7beta-OH may exert its pro-atherogenic effect by inhibiting glutathione synthesis and nitric oxide production by macrophages present in the arterial wall and thus, impair the cellular antioxidant defense system.

Animals↗

PubMed2001

Selenium supplementation protects from high fat diet-induced atherogenesis in rats: role of mitogen stimulated lymphocytes and macrophage NO production.

The present study was designed to demonstrate the involvement of immune response in experimental atherogenesis. The mitogenic stimulation of lymphocytes and NO production by macrophages in experimental atherogenesis were studied. Further, influence of selenium a potent antioxidant was also studied in the disease process. Three different treatment groups of rats undertaken for study were: group 1, control; group II, high fat diet (HFD) fed group and group III, HFD+Se supplemented group. Atherogenic conditions induced have already been explained earlier [Kang BPS et al. Gen Physiol Biophys, 17 (1998) 71]. Significant increase in 3H-thymidine incorporation was obtained in lymphocytes from HFD fed animals in both presence and absence of mitogen (Con-A). However, these values decreased in group III animals, which were supplemented with selenium. Similarly, NO levels with LPS+ and LPS- macrophages also found to be higher in HFD fed group and decreased in group III. These studies reveal the protective role of selenium in HFD-induced atherogenic process.

Animals↗

PubMed2000

Hyperlipidemia and type I 5'-monodeiodinase activity: regulation by selenium supplementation in rabbits.

Male New Zealand White rabbits were divided into three groups: (I) control, (II) high-fat-diet (HFD) fed, and (III) HFD fed + selenium supplemented. After 3 mo of treatment, there was a significant increase in serum cholesterol and triglycerides in the HFD-fed group as compared to the control. However in the selenium (Se)-supplemented group, the levels of serum cholesterol and triglycerides were significantly less as compared to group II. HFD feeding resulted in decreased serum Se levels, but supplementation of dietary Se along with HFD, as in group III, showed an apparent increase in its levels. The Se-dependent glutathione peroxidase (GSH-Px) activity in the liver and the aorta increased significantly in HFD-fed animals and also showed an additional significant increase on Se supplementation. Both serum T3 and T4 levels showed a significant decrease on HFD feeding. However, supplementation of Se led to a significant increase in the levels of these parameters viz-à-viz HFD-fed animals. HFD feeding significantly decreased the activity of type I iodothyronine 5'-deiodinase (5'-DI) in the liver from group II rats. On supplementation of Se along with HFD, the activity increased in the liver. However, there was no significant change in its activity in the aorta. The 5'-DI activity in the thyroid showed an opposite trend in comparison with peripheral tissues (i.e., liver). The important finding of this study is that in the hyperlipidemic state, deiodinase in the thyroid behaves in a different manner as compared to its activity in extrathyroidal tissues.

Animals↗