Biomedical subjects

R K Kale

Publications and source records attributed to R K Kale.

At least 19 recordsLinked to original sources

PubMed2005

Chemopreventive effects of mustard (Brassica compestris) on chemically induced tumorigenesis in murine forestomach and uterine cervix.

As there is a strong correlation between diet and cancer, the dietary constituents that inhibit mutagenesis and/or carcinogenesis are of paramount importance for the prevention of human cancer. In the present study, cancer chemopreventive potentials of different doses of mustard (Brassica compestris) seed mixed diets were evaluated against benzo(a)pyrene [B(a)P]-induced forestomach tumorigenesis and 3-methylcholantrene (MCA)-induced uterine cervix tumorigenesis. Results showed a significant inhibition of stomach tumour burden (tumours/ mouse) by mustard seeds. Tumour burden was 7.08 +/- 2.47 in the B(a)P-treated control group, whereas it was reduced to 1.36 +/- 1.12 (P<0.001) by the 2.5% dose and 1.18 +/- 0.87 (P<0.001) by the 5% dose of mustard seeds. The cervical carcinoma incidence, as compared to MCA-treated control group (73.33%), was reduced to nil (P<0.05) by the 5% diet of mustard seeds and to 13.33% (P<0.05) by the 7.5% diet of mustard seeds. The effect of the 2.5% and 5% mustard seed mixed diets was also examined on the antioxidant enzymes, glutathione content, lactate dehydrogenase (LDH) and lipid peroxidation in the liver of Swiss albino mice. The glutathione-S-transferase-specific activity was increased (P<0.05) by the 2.5% dose, whereas there was no significant change in the activity of DT-diaphorase. In antioxidant systems, significant elevation of the specific activities of superoxide dismutase and catalase was observed with both doses of mustard seeds (P<0.05). The level of reduced glutathione (GSH) measured as nonprotein sulphydryl content was elevated by the 2.5% dose of mustard seeds only (P<0.05). Lipid peroxidation measured as formation of thiobarbituric acid reactive substances production showed significant inhibition (P<0.05) by the 5% dose of mustard seed mixed diet. LDH activity was decreased significantly (P<0.05) by both the doses. The results strongly suggest the cancer chemopreventive potentials of mustard seeds and their ability to enhance the antioxidant defence system and in turn provide protection against the toxic effects of carcinogens. It is likely that the use of mustard seeds in the diet may contribute to reducing the risk of cancer incidence and burden in the human population.

Administration, Oral↗

PubMed2005

Chemopreventive potential of Triphala (a composite Indian drug) on benzo(a)pyrene induced forestomach tumorigenesis in murine tumor model system.

The present work is probably the first report on cancer chemopreventive potential of Triphala, a combination of fruit powder of three different plants namely Terminalia chebula, Terminalia belerica and Emblica officinalis. Triphala is a popular formulation of the Ayurvedic system of medicine. Our findings have shown that Triphala in diet has significantly reduced the benzo(a)pyrene [B(a)P] induced forestomach papillomagenesis in mice. In the short term treatment groups, the tumor incidences were lowered to 77.77% by both doses of Triphala mixed diet. In the case of long-term treatment the tumor incidences were reduced to 66.66% and 62.50% respectively by 2.5% and 5% triphala containing diet. Tumor burden was 7.27 +/- 1.16 in the B(a)P treated control group, whereas it reduced to 3.00 +/- 0.82 (p < 0.005) by 2.5% dose and 2.33 +/- 1.03 (p < 0.001) by 5% dose of Triphala. In long-term studies the tumor burden was reduced to 2.17 +/- 0.75 (p < 0.001) and 2.00 +/- 0.71 (p < 0.001) by 2.5% and 5% diet of Triphala, respectively. It was important to observe that Triphala was more effective in reducing tumor incidences compared to its individual constituents. Triphala also significantly increased the antioxidant status of animals which might have contributed to the chemoprevention. It was inferred that the concomitant use of multiple agents seemed to have a high degree of chemoprevention potential.

Animals↗

PubMed2004

Adaptive response and split-dose effect of radiation on the survival of mice.

Although the importance of radiation-induced adaptive response has been recognized in human health, risk assessment and clinical application, the phenomenon has not been understood well in terms of survival of animals. To examine this aspect Swiss albino mice were irradiated with different doses (2-10 Gy) at 0.015 Gy/s dose rate and observed on a regular basis for 30 days. Since almost 50% lethality was seen with 8 Gy, it was selected as the challenging dose for further studies. Irradiation of mice with conditioning doses (0.25 or 0.5 Gy) and subsequent exposure to 8 Gy caused significant increase in the survival of mice compared to irradiated control. The splitting of challenging dose did not influence the efficiency of conditioning doses (0.25 Gy and 0.5 Gy) to induce an adaptive response. However conditioning doses given in fractions (0.25 Gy + 0.25 Gy) or (0.5 Gy + 0.5 Gy) were able to modulate the response of challenging dose of 8 Gy. These results clearly showed the occurrence of adaptive response in terms of survival of animals. The conditioning dose given in small fractions seemed to be more effective. The findings have been discussed from a mechanistic point of view. The possible biological implications, potential medical benefits, uncertainties and controversies related to adaptive response have also been addressed

Adaptation, Physiological↗

PubMed2004

Modulation of antioxidant potential in liver of mice by kernel oil of cashew nut (Anacardium occidentale) and its lack of tumour promoting ability in DMBA induced skin papillomagenesis.

Cashew nut shell oil has been reported to possess tumour promoting property. Therefore an attempt has been made to study the modulatory effect of cashew nut (Anlacardium occidentale) kernel oil on antioxidant potential in liver of Swiss albino mice and also to see whether it has tumour promoting ability like the shell oil. The animals were treated orally with two doses (50 and 100 microl/animal/day) of kernel oil of cashew nut for 10 days. The kernel oil was found to enhance the specific activities of SOD, catalase, GST, methylglyoxalase I and levels of GSH. These results suggested that cashew nut kernel oil had an ability to increase the antioxidant status of animals. The decreased level of lipid peroxidation supported this possibility. The tumour promoting property of the kernel oil was also examined and found that cashew nut kernel oil did not exhibit any solitary carcinogenic activity.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2004

Cancer preventive potential of Momordica charantia L. against benzo(a)pyrene induced fore-stomach tumourigenesis in murine model system.

Bitter melon ( Momordica charantia Linnaeus) fruit extract was tested against 3,4 benzo(a)pyrene [B(a)P] induced forestomach papillomagenesis in Swiss albino mice. Extract of M. charantia in two concentrations, 2.5 and 5% of standard mice feed was used for the short-term and long-term studies. A significant decrease in tumour burden was observed in short and long-term treatment. Also, total tumour incidence reduced to 83.33% with 2.5% dose and 90.90% with 5% dose in short term treatment, while in long-term treatment tumor incidence decreased to 76.92% with 2.5% dose and 69.23% with 5% dose of M. charantia. The possible mechanism involved in the cancer chemoprevention has also been discussed.

Animals↗

PubMed2003

Role of Ca2+ in radiation-induced damage in murine splenocytes.

PURPOSE: To address the links between calcium, peroxidation, cell damage and death and the response of the enzymes involved in free radical metabolism, in splenocytes of mice irradiated with gamma-rays. MATERIALS AND METHODS: Splenocytes of Swiss albino mice were irradiated with various doses (0-7 Gy) of gamma-rays (60Co) at a dose-rate of 0.0575 Gy s(-1). Membrane peroxidation and fluidity were determined by the thiobarbituric acid-reactive substances (TBARS) method, and fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH), respectively. Apoptosis was analysed by nucleosomal ladder formation and activity of NF-kappaB by electrophoretic mobility shift assay (EMSA). The specific activities of the antioxidant enzymes, lactate dehydrogenase (LDH), levels of nitric oxide (NO*) and glutathione were determined spectrophotometrically. Modulatory effects of Ca2+ were examined at 3 Gy using different concentrations (1, 3 and 5 mM) in the presence or absence of the ionophore A23187. RESULTS: Irradiation of splenocytes resulted in enhanced peroxidative damage. membrane fluidity, apoptosis and DNA binding activity of NF-kappaB. The specific activities of LDH and antioxidant enzymes superoxide dismutase (SOD), DT-diaphorase (DTD), glutathione S-transferase (GST) and levels of glutathione (GSH) and NO* were increased with radiation dose up to 4Gy. Ca2+ augmented the radiation-induced responses. The presence of ionophore A23187 potentiated the modulatory effects of Ca2+. CONCLUSIONS: These findings show that Ca2+ augments radiation damage and is more effective intracellularly. Ca2+, peroxidation, cellular damage and apoptosis are possibly interlinked through signals, as is evident from the increased activity of NF-kappaB and generation of NO*. The enhanced antioxidant status suggests an attempt made by the irradiated cells to maintain their normal functions.

Animals↗

PubMed2003

Post-irradiation free radical generation: evidence from the conversion of xanthine dehydrogenase into xanthine oxidase.

The xanthine oxidoreductase (XOR) system which consists of xanthine dehydrogenase (XDH) and xathine oxidase (XO), is one of the major sources of free radicals in biological systems. The XOR system is pre-dominantly present as XDH in normal tissues and converts into the free radical generating XO-form in the damaged tissue. Therefore, the XO-form of the XOR system is expected to be mainly found in radiolytically damaged tissues. In such an event, XO may catalyze the generation of free radicals and potentiate radiation effects in the post-irradiation period. Recent findings on the effect of ionizing radiation on the XOR system in the liver of mice, peroxidative damage and lactate dehydrogenase support this possibility. From these results it has been hypothesized that free radical generating systems could be activated in the radiolytically damaged cell and in turn contribute to the cause and complications of late effects and their persistence in post-irradiation period. This aspect may have great significance in the understanding of radiation-induced damages. It may also have serious implication in various fields like radiation therapy, health physics, carcinogenesis, space travelling radiation exposures and post nuclear accident care. Further, it is suggested that efforts need to be made to search more system(s) which could be activated particularly at lower doses of radiation to generate free radicals in the post-exposure period.

Animals↗

PubMed2002

Modulation of radiation-induced changes in the xanthine oxidoreductase system in the livers of mice by its inhibitors.

The xanthine oxidoreductase (XOD) system, which consists of xanthine dehydrogenase (XDH) and xanthine oxidase (XO), is one of the major sources of free radicals in biological systems. The XOD system is present predominantly in the normal tissues as XDH. In damaged tissues, XDH is converted into XO, the form that generates free radicals. Therefore, the XO form of the XOD system is expected to be found mainly in radiolytically damaged tissue. In this case, XO may catalyze the generation of free radicals and potentiate the effect of radiation. Inhibition of the XOD system is likely to attenuate the detrimental effects of ionizing radiation. We have examined this possibility using allopurinol and folic acid, which are known inhibitors of the XOD system. Swiss albino mice (7-8 weeks old) were given single doses of allopurinol and folic acid (12.5-50 mg/kg) intraperitoneally and irradiated with different doses of gamma radiation at a dose rate of 0.023 Gy/s. The XO and XDH activities as well as peroxidative damage and lactate dehydrogenase (LDH) were determined in the liver. An enhancement of the activity of XO and a simultaneous decrease in the activity of XDH were observed at doses above 3 Gy. The decrease in the ratio XDH/XO and the unchanged total activity (XDH + XO) suggested the conversion of XDH into XO. The enhanced activity of XO may potentiate radiation damage. The increased levels of peroxidative damage and the specific activity of LDH in the livers of irradiated mice supported this possibility. Allopurinol and folic acid inhibited the activities of XDH and XO, decreased their ratio (XDH/XO), and lowered the levels of peroxidative damage and the specific activity of LDH. These results suggested that allopurinol and folic acid have the ability to inhibit the radiation-induced changes in the activities of XDH and XO and to attenuate the detrimental effect of this conversion, as is evident from the diminished levels of peroxidative damage and the decreased activity of LDH.

Allopurinol↗

PubMed2001

Modulation of glyoxalase, glutathione S-transferase and antioxidant enzymes in the liver, spleen and erythrocytes of mice by dietary administration of fenugreek seeds.

There is a growing interest in understanding the biological effect of time-tested folk medicinal plants. In the present work, the effect of dietary administration of fenugreek seeds on the glyoxalase system and antioxidant enzymes as well as levels of glutathione (GSH) have been examined in different tissues of mice. Swiss albino mice were fed with diet containing powdered fenugreek for 4 weeks. The mode and magnitude of effect was found to depend on the dose of fenugreek and type of tissue. The diet containing 1 and 2% of fenugreek enhanced the specific activity of gly I, whereas 5 and 10% inhibited its activity in the liver. However, on the other hand, the specific activity of gly II decreased continuously with dose. Dietary administration of fenugreek seeds resulted in an increase of GSH levels and the glutathione S-transferase (GST) activity in the liver. Fenugreek (1 and 2%) showed no appreciable change in superoxide dismutase (SOD) and catalase. However, 5 and 10% doses of fenugreek supplementation inhibited their activities. In the case of spleen, a significant change in gly I was observed only at 10% fenugreek. In addition, a significant increase was also observed with GSH levels. Fenugreek treatment up to 5% showed a small but consistent increase in erythrocytes. In the case of GST, the activity enhanced with dose. Significant elevation of catalase activity was observed with a 10% dose of fenugreek. The significance and relevance of these findings are suggested in relation to mechanistic aspects.

Animals↗

PubMed2001

Radiomodification of glyoxalase I in the liver and spleen of mice: adaptive response and split-dose effect.

Glyoxalase system, particularly glyoxalase I (Gly I) plays an important role in regulation of cell division and is considered to be a metabolic indicator of cell proliferation. The glyoxalase system is likely to have a close link with cellular radiosensitivity. Therefore, we have examined the effect of adaptive and split-dose of y-rays on the activity of Gly I in the liver and spleen of mice. For the adaptive response studies, mice pre-treated with a conditioning dose of 0.5 Gy were given a challenging dose of 4 Gy at varying time intervals. In the split-dose studies, a dose of 4 Gy was delivered into two equal fractions and spaced at different time intervals. The results show that pre-exposure to a conditioning dose or the fractionation of total dose decreased the specific activity of Gly I in the liver and spleen of mice. The decreased activity of Gly I was suggestive of protective action induced by the conditioning dose and fractionation of dose. The similar pattern of radiation response of Gly I probably supported the possibility of involvement of a common pathway in the radiation-induced adaptive and split-dose effect. From these observations a close link between the Gly I and the adaptive-response as well as the split-dose effect is speculated. Since, the glyoxalase system is vital for a variety of biological functions including cell division and repair, the present findings may have relevance in understanding the dose-fractionation as well as the biological defence induced by low doses of radiations.

Animals↗

PubMed2001

Radiation induced oxidative stress: II studies in liver as a distant organ of tumor bearing mice.

Since the radiation dose tolerance of normal tissues/organs away from the site of tumor influences the success of radiation therapy of cancer, and antioxidant status is likely to be one of the factors to determine the tolerance; the radioresponse of antioxidant enzymes has been examined in the liver as a representative distant organ in the tumor-bearing mice. Swiss albino male mice (7-8 weeks old) with Ehrlich solid tumor in the thigh pad were irradiated with different doses of gamma-radiation (0-9 Gy) at a dose rate of 0.0153 Gy/s and the specific activities of enzymes involved in the free radical metabolism were determined in the liver. Except GST, the activities of SOD, DTD and Gly I as well as the GSH content were found to be higher in the liver of tumor-bearing mice compared to the non-tumor bearing mice. The catalase activity progressively decreased with dose in both the groups of mice. However, the activity was relatively higher in the liver of tumor- bearing mice than the control. Thus, the radioresponse of antioxidant enzymes seemed to be significantly different in the liver of tumor-burdened mice compared to controls. The enhanced activities might be due to relatively more damage caused by radiation. The higher levels of NO* and peroxidative damage in the liver of tumor-bearing mice probably suggest this possibility. These findings of the present work might have some serious implications as the increased radiation-damage of the distant normal organs (due to tumor burden) is likely to adversely affect the therapeutic gain.

Animals↗

PubMed2001

Radiation induced oxidative stress: I. Studies in Ehrlich solid tumor in mice.

Understanding the response of tumors to ionizing radiation might potentially lead to improvement in tumor control and patient morbidity. Since the antioxidant status is likely to be linked to radioresponse, its modulation needs to be examined. Therefore, Swiss albino male mice (7-8 weeks old) with Ehrlich solid tumors were irradiated with different doses of gamma rays (0-9 Gy) at a dose rate of 0.0153 Gy/s; and enzymes involved in antioxidant functions were determined in the tumors. Radiation effects in terms of oxidative damage, LDH, nitric oxide and DNA fragmentation were also examined. In tumors, the specific activity of SOD was increased with dose but declined 6 Gy onwards. GST, DTD and GSH showed an almost progressive increase. These enhanced activities might have resulted from the increased protein expression. This possibility was supported by the Western Blot analysis for GST protein. These changes might be closely linked to the radiation-induced oxidative stress as reflected by the enhanced levels of peroxidative damage, DNA fragmentation, LDH activity and nitric oxide levels. These findings may have relevance to radiation therapy of cancer as the elevated antioxidant status of irradiated tumors is likely to limit the effectiveness of radiation dose and adversely affect the therapeutic gain.

Animals↗

PubMed2001

Radiation induced peroxidative damage: mechanism and significance.

An interest has been generated in free radicals after the discovery of superoxide dismutase. These free radicals cause a number of diseases and are involved in the detrimental effect of ionizing radiation. Efforts have been made to understand their role in damage and death of the cell using lipid peroxidation process. Lipid peroxidation is an important effect of radiation on membranes, which apart from DNA, are critical targets of radiation action. This paper addresses the basic mechanism of radiation induced lipid peroxidation. Various factors, which determine the mode and magnitude of lipid peroxidation, are also discussed. Lipid peroxidation is shown to have importance in understanding the modifications of radiation effects. Efforts are made to show similarities between radiolytic and non-radiolytic lipid peroxidation. Recent findings related to the close link between radiation-induced lipid peroxidation and apoptosis are likely to open new avenues for future research and to develop new approaches for radiomodification of biological effects.

Animals↗

PubMed2000

Spectral light quality affects protein profile of Synechococcus sp. PCC 7942: a comparative 2-dimensional gel electrophoresis (2-DGE) analysis.

We report here a comparative analysis of the effect of blue (450 nm), red (660 nm), and white light (400-700 nm) on the protein profile of cyanobacteria Synechococcus sp. PCC 7942. In vivo labeling of cells with [(35)S] methionine and their subsequent analysis by two-dimensional gel electrophoresis (2-DGE) showed that eight polypeptides were unique to dark adapted cells, ten were blue light specific, and four were specifically induced in red light. The results show that Synechococcus sp. respond to various light treatments rapidly and synthesize new polypeptides in dark and blue/red light.

Bacterial Proteins↗

PubMed2000

Effects of free radicals on cytosolic creatine kinase activities and protection by antioxidant enzymes and sulfhydryl compounds.

The main purpose of this study was to investigate the effect of free radicals and experimental diabetes on cytosolic creatine kinase activity in rat heart, muscle and brain. Hydrogen peroxide decreased creatine kinase activity in a dose dependent manner which was reversed by catalase. Xanthine/xanthine oxidase, which produces superoxide anion, lowered the creatine kinase activity in the same manner whose effect was protected by superoxide dismutase. N-acetylcysteine and dithiothreitol also significantly ameliorated the effect of Xanthine/xanthine oxidase and hydrogen peroxide. Experimental diabetes of twenty-one days (induced by alloxan), also caused a similar decrease in the activity of creatine kinase. This led us to the conclusion that the decrease in creatine kinase activity during diabetes could be due to the production of reactive oxygen species. The free radical effect could be on the sulfhydryl groups of the enzyme at the active sites, since addition of sulfhydryl groups like N-acetylcysteine and dithiothreitol showed a significant reversal effect.

Acetylcysteine↗

PubMed2000

Radiomodfication of xanthine oxidoreductase system in the liver of mice by phenylmethylsulfonyl fluoride and dithiothreitol.

The widely distributed xanthine oxidoreductase (XOR) system has been shown to be modulated upon exposure of animals to ionizing radiation through the conversion of xanthine dehydrogenase (XDH) into xanthine oxidase (XO). In the present work, radiomodification of the XOR system by phenylmethylsulfonyl fluoride (PMSF) and dithiothreitol (DTT) was examined using female Swiss albino mice which were irradiated with gamma rays at a dose rate 0.023 Gy s(-1). PMSF, a serine protease inhibitor, and DTT, the sulfhydryl reagent, were administered intraperitoneally prior to irradiation. The specific activities of XDH and XO as well as the XDH/XO ratio and the total activity (XDH+XO) were determined in the liver of the mice. The inhibition of XO activity, restoration of XDH activity, and increase in the XDH/XO ratio upon administration of PMSF were suggestive of irreversible conversion of XDH into XO mediated through serine proteases. The biochemical events required for the conversion were probably initiated during the early phase of irradiation, as the treatment with PMSF immediately after irradiation did not have a modulatory effect. Interestingly, DTT was not effective in modulating radiation-induced changes in the XOR system or oxidative damage in the liver of mice. The DTT treatment resulted in inhibition of the release of lactate dehydrogenase. However, the protection appears to be unrelated to the formation of TBARS. On the other hand, the presence of PMSF during irradiation inhibited radiation-induced oxidative damage and radiation-induced increases in the specific activity of lactate dehydrogenase. These findings suggest that a major effect of ionizing radiation is irreversible conversion of xanthine to xanthine oxidase.

Animals↗

PubMed1999

Modulation of radioresponse of glyoxalase system by curcumin.

Human beings have been exposed to radiation for many years. It is quite possible that antioxidant phytochemicals consumed in their diet might be providing a variable degree of radioprotection. However, their radiomodifying ability is not well understood. In the present work, curcumin (diferuloyl methane), a phytochemical present in the rhizome of Curcuma longa Linn. has been examined for its radioprotective property using the glyoxalase system which is vital for various biological functions. Curcumin (5, 25 and 50 mg/kg body weight) in olive oil was given orally to Swiss albino male mice (7-8 weeks old) daily for 2 weeks and irradiated with different doses of gamma-radiation (0-6 Gy) at 0.027 Gy per second dose rate on last day of the treatment. The specific activities of glyoxalase I and II were determined in the liver and spleen. The treatment of curcumin prior to irradiation restored the specific activity of glyoxalase system to almost the control level which was suggestive of the radioprotective ability of curcumin. Free radical scavenging and electron/hydrogen donation are probable attributes for the protective effect of curcumin.

Animals↗

PubMed1999

Influence of gamma-rays on the mouse liver cytochrome P450 system and its modulation by phenothiazine drugs.

PURPOSE: Phenothiazine drugs have been found to sensitize hypoxic cancer cells while offering protection to normal cells. Since phenothiazines are known to induce the cytochrome P450 system, its radiomodulation by phenothiazines has been examined. MATERIALS AND METHODS: Mice were administered phenothiazines intraperitoneally and irradiated with different doses of gamma-rays at 1.38 Gy/min. The activities of NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase, the content of cytochrome P450 and b5, the extent of lipid peroxidation as well as the activities of LDH, XO, SOD, GST and DTD were determined in the liver. RESULTS: The levels of different components of the cytochrome P450 system and antioxidant enzymes were enhanced up to 5 Gy and decreased thereafter. However, a progressive increase was noticed in peroxidative damage and the activities of LDH and XO. Administration of phenothiazines enhanced the radiation effect on components of the cytochrome P450 system (except NADH-cytochrome b5 reductase) and the activities of SOD, GST and DTD. Concomitantly, phenothiazines inhibited lipid peroxidation, LDH and XO. CONCLUSIONS: Activation of the cytochrome P450 system by phenothiazines leading to the enhancement of antioxidant potential of animals and free-radical scavenging are attributes of the radioprotective action of phenothiazines.

Animals↗