Biomedical subjects

M Bagchi

Publications and source records attributed to M Bagchi.

At least 91 records · Page 5Linked to original sources

PubMed1994

Smokeless tobacco induced increases in hepatic lipid peroxidation, DNA damage and excretion of urinary lipid metabolites.

The possible role of reactive oxygen species in the toxicity of smokeless tobacco (ST) was explored. The effects of an aqueous smokeless tobacco extract (STE) at doses of 125, 250 and 500 mg STE/kg in rats on the induction of hepatic mitochondrial and microsomal lipid peroxidation and the incidence of hepatic nuclear DNA damage 24 hours post treatment were examined. Dose-dependent increases of 1.8, 2.3 and 4.4-fold in mitochondrial and 1.5, 2.1 and 3.6-fold in microsomal lipid peroxidation occurred at 125, 250 and 500 mg STE/kg, respectively, relative to control values. At these same three doses of STE, 1.3, 1.4 and 2.7-fold increases in hepatic DNA single-strand breaks occurred relative to control values. STE administration also resulted in significant increases in excretion of urinary metabolites. Urinary excretion of the four lipid metabolites malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT) and acetone (ACON) was monitored by HPLC for 72 hours after treatment of rats with 125 and 250 mg STE/kg. Increases occurred in the excretion of the four lipid metabolites at every dose and time point with maximum increases in the excretion of all lipid metabolites being observed between 12 and 24 hours post treatment. The results suggest the involvement of an oxidative stress in the toxicity of STE.

Acetone↗

PubMed1993

Extraskeletal mesenchymal chondrosarcoma of the orbit.

Mesenchymal chondrosarcoma, an uncommon lesion of bone and extraskeletal tissue, is rare in the orbit. A case of extraskeletal mesenchymal chondrosarcoma of the orbit in a 28-year-old woman presenting with proptosis and diminution of vision in the left eye is reported. Histologically, the tumor showed areas of undifferentiated mesenchymal cells with islands of cartilage. Immunohistochemical analysis for S-100 protein showed focal positivity in chondroid areas. The eye was preserved and the patient has good vision after 2 years of follow-up.

Adult↗

PubMed1993

Effects of carbon tetrachloride, menadione, and paraquat on the urinary excretion of malondialdehyde, formaldehyde, acetaldehyde, and acetone in rats.

Excretions of the lipid peroxidation products, formaldehyde (FA), acetaldehyde (ACT), malondialdehyde (MDA), and acetone (ACON), were simultaneously identified and quantitated in the urine of female Sprague-Dawley rats by gas chromatography-mass spectroscopy (GC-MS) and high pressure liquid chromatography (HPLC) following the acute administration of carbon tetrachloride, a model alkylating agent that does not induce glutathione depletion, and the redox cycling compounds paraquat and menadione. All three xenobiotics are well-known inducers of oxidative stress. Oxidative stress was induced by oral administration of single doses of 2.5 mL of carbon tetrachloride/kg, 60 mg menadione/kg, and 75 mg paraquat/kg. These doses are approximately 50% of the LD50's for the three xenobiotics. Urinary excretion of FA, ACT, MDA, and ACON increased relative to control animals following treatment with all xenobiotics. Over the 48 hours of the study, the greatest increases in the excretion of MDA, FA, ACT, and ACON occurred after paraquat administration, with increases of approximately 2.7-, 2.6-, 4.3-, and 11.0-fold, respectively. This technique may have wide-spread applicability as an effective biomarker for investigating altered lipid metabolism in disease states and exposure to environmental pollutants/xenobiotics.

Acetaldehyde↗

PubMed1993

Time-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on serum and urine levels of malondialdehyde, formaldehyde, acetaldehyde, and acetone in rats.

The ability of TCDD to produce lipid mobilization and alter lipid metabolism is well known. Previous studies have indicated that TCDD induces an oxidative stress and enhances lipid peroxidation. However, the products resulting from altered lipid metabolism in response to TCDD have not been studied. We have examined the time-dependent changes in serum and urine levels of malondialdehyde, formaldehyde, acetaldehyde, and acetone in response to a single oral 50 micrograms/kg dose of TCDD in rats. The changes in these four metabolic products were quantitated by high-pressure liquid chromatography (HPLC). The effects of TCDD were compared in ad libitum-fed control animals and pair-fed animals. Serum and urine levels of the four metabolites were assayed on Days 0, 3, 6, 9, and 12. Following TCDD administration, significant increases in the four metabolites present in serum and urine were observed at all time points. For example, on Day 6 post-treatment malondialdehyde, formaldehyde, acetaldehyde, and acetone increased approximately 1.8-, 1.4-, 2.0-, and 3.0-fold in serum, respectively, and 1.3-, 1.4-, 1.6-, and 2.0-fold in urine, respectively, relative to pair-fed control animals. Increases in the serum and urine levels of the four metabolites were significantly greater for TCDD animals than for pair-fed control animals at most time points. When the serum levels of malondialdehyde as determined by HPLC were compared with the results obtained by the thiobarbituric acid (TBA) colorimetric method, similar time courses were observed although higher results were obtained for the less specific TBA method. The results clearly demonstrate that TCDD causes markedly elevated serum and urine levels of four specific products associated with lipid metabolism.

Acetaldehyde↗

PubMed1993

Comparative studies on lipid peroxidation and DNA-single strand breaks induced by lindane, DDT, chlordane and endrin in rats.

1. A variety of structurally dissimilar polyhalogenated cyclic hydrocarbons produce similar toxic effects. The molecular mechanisms involved in the production of these toxic manifestations is not known. 2. We have proposed that reactive oxygen species may be involved, and have therefore examined the time-dependent effects of lindane (30 mg/kg), DDT (40 mg/kg), chlordane (120 mg/kg), and endrin (4.5 mg/kg) on the production of hepatic mitochondrial and microsomal lipid peroxidation and DNA single strand breaks, two indices of oxidative stress. 3. All four xenobiotics resulted in significant increases in hepatic lipid peroxidation and DNA damage. Earliest (6 hr) increases in both lipid peroxidation and DNA damage were observed following lindane administration. Time-dependent increases in both parameters were observed following endrin administration. 4. Maximum increases in DNA single strand breaks of 2.8- and 2.5-fold were observed 12 hr after DDT and chlordane administration, respectively, while a 4.4-fold increase was observed 24 hr after endrin administration. 5. The results demonstrate that the four structurally dissimilar polyhalogenated hydrocarbons produce oxidative tissue damage which may contribute to the toxic manifestations of these xenobiotics, and exhibit different toxicokinetic properties.

Animals↗

PubMed1993

Comparative effects of endrin on hepatic lipid peroxidation and DNA damage, and nitric oxide production by peritoneal macrophages from C57BL/6J and DBA/2 mice.

1. Endrin is a polyhalogenated cyclic hydrocarbon which produces hepatic and neurologic toxicity. In order to further assess the mechanism of toxicity of endrin, the dose-dependent effects of endrin on hepatic lipid peroxidation and DNA damage, and nitric oxide (NO) production by peritoneal exudate cells (primarily macrophages) were investigated in C57BL/6J and DBA/2 mice which vary at the Ah receptor genetic locus. C57BL/6J mice are dioxin-responsive, while DBA/2 mice are dioxin-insensitive. 2. Mice of both strains were treated with 0, 1, 2 or 4 mg endrin kg-1 as a single oral dose in corn oil, and the animals were killed 24 hr post-treatment. At doses of 1, 2 and 4 mg endrin kg-1 in C57BL/6J mice, hepatic mitochondrial lipid peroxidation increased 1.2-, 2.2- and 3.2-fold, respectively, and 1.8-, 2.3- and 3.5-fold with microsomes, respectively. At these same doses in DBA/2 mice, hepatic mitochondrial lipid peroxidation increased 1.3-, 2.0- and 2.6-fold, respectively, and 1.5-, 1.9- and 2.5-fold with microsomes, respectively. 3. Increases of 2.3-, 2.4- and 4.9-fold were observed in hepatic DNA damage (elution constants) in C57BL/6J mice at doses of 1, 2 and 4 mg endrin kg-1, respectively, while at these same three doses, increases of 1.9-, 2.1- and 2.3-fold were observed for DBA/2 mice, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Production of reactive oxygen species by peritoneal macrophages and hepatic mitochondria and microsomes from endrin-treated rats.

Recent studies have shown that the administration of endrin to rodents induces lipid peroxidation in various tissues and decreases glutathione content. These results suggest that endrin produces reactive oxygen species and/or free radicals. We have therefore examined the effect of endrin (4.5 mg/kg) on the production of reactive oxygen species by peritoneal macrophages and hepatic mitochondria and microsomes in rats. The effects of endrin on hepatic mitochondrial and microsomal lipid peroxidation and membrane fluidity as well as the incidence of hepatic nuclear DNA damage were also examined. Twenty-four hours after endrin administration, significant increases in the production of chemiluminescence by the three tissue fractions were observed. Furthermore, peritoneal macrophages from endrin-treated animals resulted in 3.0- and 2.8-fold increases in cytochrome c and iodonitrotetrazolium (INT) reduction, indicating enhanced production of superoxide anion. Endrin administration also resulted in significant increases in lipid peroxidation of mitochondrial and microsomal membranes as well as decreases in the fluidity of these two membranous fractions. A significant increase in hepatic nuclear DNA single-strand breaks also occurred in response to endrin administration. The results indicate that macrophage, mitochondria, and microsomes produce reactive oxygen species following endrin administration, and these reactive oxygen species may contribute to the toxic manifestations of endrin.

Animals↗

PubMed1993

Protective effects of antioxidants against endrin-induced hepatic lipid peroxidation, DNA damage, and excretion of urinary lipid metabolites.

Oxidative stress is believed to play a pivotal role in endrin-induced hepatic and neurologic toxicity. Therefore, the effects of the antioxidants vitamin E succinate and ellagic acid have been examined on hepatic lipid peroxidation, DNA single-strand breaks (SSB), and the urinary excretion of lipid metabolites following an acute oral dose of 4.5 mg endrin/kg. Groups of rats were pretreated with 100 mg/kg vitamin E succinate for 3 d followed by 40 mg/kg on day 4, or 6.0 mg ellagic acid/kg for 3 d p.o. followed by 3.0 mg/kg on day 4 or the vehicle. Endrin was administered p.o. on day 4 2 hr after treatment with the antioxidant. All animals were killed 24 h after endrin administration. Vitamin E succinate pretreatment decreased the endrin-induced increase in hepatic mitochondrial and microsomal lipid peroxidation by approximately 60% and 40%, respectively. Ellagic acid pretreatment reduced the endrin-induced increased in mitochondrial and microsomal lipid peroxidation by approximately 76 and 79%, respectively. Both vitamin E succinate and ellagic acid alone produced small but nonsignificant decreases in hepatic mitochondrial and microsomal lipid peroxidation. A 3.3-fold increase in the incidence of hepatic nuclear DNA single-strand breaks was observed 24 h after endrin administration. Pretreatment of rats with vitamin E succinate, vitamin E, and ellagic acid decreased endrin-induced DNA-SSB by approximately 47%, 22%, and 21%, respectively. Pretreatment of rats with vitamin E succinate decreased the endrin-induced increase in the urinary excretion of malondialdehyde, acetaldehyde, formaldehyde, and acetone by approximately 68, 65, 70, and 55%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗

PubMed1993

In vitro induction of reactive oxygen species by 2,3,7,8-tetrachlorodibenzo-p-dioxin, endrin, and lindane in rat peritoneal macrophages, and hepatic mitochondria and microsomes.

Hepatic mitochondria and microsomes as well as peritoneal macrophages from female Sprague-Dawley rats were incubated for up to 30 min at 37 degrees C in the presence of 0-200 ng/ml 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), endrin (1,2,3,4,10,10-hexachloro-6,7-epoxy-1,4,4 alpha,5,6,7,8,8 alpha-octahydroendo, endo-1,4:5,8-dimethanonaphthalene), and lindane (hexachlorocyclohexane). Production of reactive oxygen species was determined by chemiluminescence and cytochrome c reduction, while potential tissue damage was assessed by alterations in membrane fluidity. Chemiluminescence, a sensitive but nonspecific measure of free radical generation, increased 40-70% when macrophages (3 x 10(6) cells/ml), mitochondria and microsomes (1 mg/ml) were incubated with the three polyhalogenated cyclic hydrocarbons (PCH). Maximum increases in chemiluminescence occurred within 5-10 min of incubation and persisted for over 30 min. The cytochrome c reduction assay is most specific for superoxide anion production. When hepatic mitochondria were incubated with endrin and lindane for 15 min at 100 ng/ml, increases in cytochrome c reduction of 6.5- and 7.5-fold occurred, respectively, while when microsomes were incubated with these same two PCH, increases in cytochrome c reduction of 8.6- and 11.6-fold occurred, respectively. When mitochondria, microsomes, and macrophages were incubated with TCDD under identical conditions, small increases in superoxide anion production were detected. Changes in microsomal membrane fluidity were determined spectrofluorometrically following incubation with the three PCH using diphenyl-1,3,5-hexatriene as the fluorescent probe. TCDD, endrin, and lindane enhanced microsomal membrane apparent microviscosity by 2.3-, 2.1-, and 2.5-fold, respectively, indicating a significant decrease in membrane fluidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Carbon-tetrachloride-induced urinary excretion of formaldehyde, malondialdehyde, acetaldehyde and acetone in rats.

Previous studies have demonstrated that the hepatotoxin carbon tetrachloride rapidly promotes lipid peroxidation and inhibits microsomal calcium sequestration, microsomal glucose-6-phosphatase activity and cytochrome P-450. Due to its profound effects on lipid peroxidation, we have examined the oral administration of 2.5 ml/kg carbon tetrachloride on the urinary excretion of the lipid metabolites formaldehyde, malondialdehyde, acetaldehyde and acetone. Urine samples were collected up to 48 h after treatment. The urinary metabolites were identified and quantitated by gas chromatography-mass spectrometry and high-pressure liquid chromatography. Time-dependent increases in the urinary excretion of the four metabolites were observed after carbon tetrachloride administration. At 48 h after treatment, the increases in the excretion of malondialdehyde, formaldehyde, acetaldehyde and acetone were approximately 55, 78, 57 and 268%, respectively, relative to control values. The data were expressed in nanomoles per kilogram body weight per 4.5 h. The results clearly demonstrate that carbon tetrachloride increases the urinary excretion of four lipid metabolites which may serve as noninvasive biomarkers of xenobiotic-induced lipid peroxidation.

Acetaldehyde↗

PubMed1993

Elemental studies in rat lens during galactose cataract reversal.

Alterations in elemental composition of the normal lens have been reported to accompany galactose cataract development in rats. In this report we present the changes in regional distribution of Na, K, Cl, P, S and Ca during the reversal of galactose-induced cataracts. Elemental X-ray maps of lenses from young female Sprague Dawley rats fed 50% galactose for 20 days were examined at 0, 20, 40 and 90 days following the transfer of galactose fed rats to Purina Rat Chow diet. Reinstatement of normal elemental distribution accompanied the progression of lens transparency. By 90 days on the rat chow diet, K had increased and Na, Cl and Ca had decreased so that a near normal lenticular distribution of these elements was established. The reinstatement of elemental distribution during cataract reversal followed a pattern similar to that observed for alterations during cataract development, initiating near the equatorial surface and expanding centrally. The correlation between the alterations in the distribution of the elements studied and our previously reported morphological investigation of lenses during galactose cataract reversal is discussed in this report.

Animals↗

PubMed1993

Lipid peroxidation in hepatic microsomal membranes isolated from mice in health and in experimental leishmaniasis.

Normal hepatic microsomal membranes when exposed in vitro to different free radicals, cause membrane damage by lipid peroxidation which could be monitored by the analysis of malonaldehyde formation and measurement of membrane microviscosity. Lipid peroxidation in vivo, when examined in hepatic microsomal membranes in experimental Leishmaniasis, reveals a direct relationship between membrane microviscosity and the extent of lipid peroxidation. Scavengers of free radicals and peroxides such as superoxide dismutase (SOD) for O2.-, mannitol for (OH.) and catalase for H2O2 in modest amounts were used for preventing the membrane damage caused by lipid peroxidation.

Animals↗

PubMed1992

Effect of endrin on the hepatic distribution of iron and calcium in female Sprague-Dawley rats.

The distribution of iron and calcium in hepatic subcellular fractions of female rats treated with endrin (1,2,3,4,10,10-hexachloro-6,7-epoxy-1,4,4 alpha,5,6,7,8,8 alpha- octahydroendo,endo-1,4:5,8-dimethanonaphthalene) was determined. Endrin in corn oil was administered orally to rats in single doses of 3, 4.5, or 6 mg/kg, and the animals were killed at 0, 12, 24, 48, or 72 hr post-treatment. Iron and calcium were determined by atomic absorption spectroscopy. The administration of endrin increased the iron content of mitochondria and decreased the iron content of microsomes and nuclei. Significant increases occurred in the calcium content of mitochondria, microsomes, and nuclei. Thus, the results indicate that with respect to the subcellular distribution of iron and calcium, endrin produces differential effects. Vitamin E succinate administration partially prevented the endrin-induced hepatic alterations in iron and calcium homeostasis. Endrin also produced dose- and time-dependent increases in the liver and spleen weight/body weight ratios, while decreasing the thymus weight/body weight ratios. The altered distribution of calcium and iron may contribute to the broad range of effects of endrin.

Analysis of Variance↗

PubMed1992

Growth regulation of the mammalian ocular lens by vitreous humor.

Experiments were performed in our laboratory to study the effects of a mammalian 8 kD vitreous humor (VH) factor on the DNA synthesis and mitosis of the epithelial cells of organ cultured rabbit lens. The 8 kD polypeptide factor was purified from mature rabbit vitreous humor by liquid chromatography. Proliferative activities of the epithelial cells of organ cultured lenses were stimulated by 3% rabbit serum. The data from our experiments depicted that the 8 kD VH factor effectively inhibits DNA synthesis and mitosis by the epithelial cells of the organ cultured lens. Our experiments also showed that this 8 kD VH factor can maintain its growth inhibitory activity even when heated for 3 min at 95 degrees C. The growth inhibitory effect of the 8 kD VH factor was dose dependent. Using iodinated vitreal proteins it was demonstrated that the VH proteins are able to enter or bind to lens epithelial cells. The growth inhibitory effect of the 8 kD VH factor was also tested on tissue cultured lens epithelial cells. These experiments showed that the 8 kD VH factor has no growth inhibitory effect on the tissue cultured lens epithelial cells. This experiment has been repeated many times using different concentrations of the factor. These observations suggest that the 8 kD VH factor may have receptors in the lens capsular material (extracellular matrix) and the factor-receptor binding is essential for the growth inhibitory effect.

Animals↗

PubMed1992

The mammalian iris-ciliary complex affects organization and synthesis of cytoskeletal proteins of organ and tissue cultured lens epithelial cells.

A water soluble growth inhibitor was isolated from the mammalian ocular iris-ciliary complex. The molecular weight of this protein is 10 kD or lower as determined by ultrafiltration fractionation. The iris-ciliary (IC) complex water soluble protein(s) significantly inhibits synthesis of lower molecular weight proteins of the epithelial cells of the organ cultured mammalian ocular lens. It was also found that this inhibitory effect of IC is mediated via the structural organization of the lens. Monolayer cultures of the lens epithelial cells exposed to IC did not manifest any inhibition of their protein synthesis. Moreover, these tissue cultured lens epithelial (TCLE) cells showed a significant increase in their protein synthetic activities in response to the presence of IC factors in the culture medium. It is postulated that the IC activity is modulated via either the lens capsule, an extracellular matrix, or due to the specific organization of the intact lens. The specific effects of IC on the cytoskeletal organization and synthesis in the organ cultured lens epithelial (OCLE) and TCLE cells were also examined. Both groups, treated with IC factors, manifested significant alterations in their protein synthetic activities and cytoskeletal architecture. The 3H-leucine incorporation experiments showed that alpha-actin and alpha-tubulin synthesis is partially inhibited by IC factors in OCLE cells but vimentin synthesis is not, whereas in TCLE cells all of them showed increased synthesis in response to IC factors. Turnover rates of these proteins in both OCLE and TCLE cells were also computed. The immunofluorescence and microscopic evaluation of OCLE and TCLE cells exposed to IC factors illustrated significant alteration in the cytoarchitecture of the filaments. We demonstrate that an inhibitor(s) molecule of 10 kD or lower size isolated from IC inhibited protein synthesis of OCLE cells and stimulated protein synthesis in TCLE cells. The IC factor also affects the synthesis and organization of cytoskeletal filaments of both the OCLE and TCLE cells.

Actins↗

PubMed1992

Endrin-induced increases in hepatic lipid peroxidation, membrane microviscosity, and DNA damage in rats.

Endrin is a polyhalogenated cyclic hydrocarbon pesticide which produces hepatic and neurologic toxicity. Previous studies have indicated that endrin induces hepatic lipid peroxidation. In order to further assess the possible role of lipid peroxidation in the toxicity of endrin, the dose- and time-dependent effects of endrin on hepatic lipid peroxidation, membrane microviscosity and DNA damage in rats were examined. Rats were treated with 0, 3.0, 4.5, or 6.0 mg endrin/kg as a single oral dose in corn oil, and the animals were killed 0, 12, 24, 48, or 72 h post-treatment. Dose-dependent increases in hepatic mitochondrial and microsomal lipid peroxidation and microviscosity as well as nuclear DNA single strand breaks were observed as early as 12 h post-treatment. Maximum increases in these three parameters occurred 24 h after endrin administration at all three doses. While the incidence in DNA damage decreased with time after 24 h, the incidence of lipid peroxidation and microviscosity of microsomal and mitochondrial membranes remained relatively constant. Dose- and time-dependent increases in liver and spleen weight/body weight ratios with decreases in thymus weight/body weight ratios were observed. The data indicate that endrin administration induces hepatic lipid peroxidation which may be responsible for the increased membrane microviscosity as a result of membrane damage as well as enhanced DNA damage.

Analysis of Variance↗

PubMed1992

Endrin-induced urinary excretion of formaldehyde, acetaldehyde, malondialdehyde and acetone in rats.

Previous studies have shown that endrin induces an oxidative stress in rats as demonstrated by an increase in hepatic lipid peroxidation, a decrease in glutathione content and a decrease in the activity in selenium-dependent glutathione peroxidase. We have therefore examined the effects of orally administering 1.5, 3.0, 4.5 and 6.0 mg endrin/kg on the urinary excretion of the lipid metabolites formaldehyde, malondialdehyde, acetaldehyde and acetone. The simultaneous determination of these four lipid metabolites may be a useful biomarker for assessing exposure to xenobiotics which induce an oxidative stress and enhanced lipid peroxidation. Urine samples were collected up to 72 h post-treatment. The identities of the lipid metabolites were confirmed by gas chromatography-mass spectroscopy, while the 2,4-dinitrophenylhydrazine derivatives of these metabolic products were quantitated by high pressure liquid chromatography. Maximum increases in the excretion of the four lipid metabolites occurred at approx. 24 h post-treatment at all doses with no significant increases in excretion occurring thereafter. The maximum increases in excretion of malondialdehyde, formaldehyde, acetaldehyde and acetone were approx. 160%, 93%, 121% and 162%, respectively, relative to control values. Seventy-two hours after endrin administration, the liver weight/body weight and spleen weight/body weight ratios significantly increased while the thymus weight/body weight ratio markedly decreased. The results demonstrate that endrin induces dose- and time-dependent alterations in lipid metabolism with the enhanced excretion of specific metabolic products in the urine.

Acetaldehyde↗

PubMed1992

Generation of singlet oxygen and hydroxyl radical from sodium chlorite and lactic acid.

Reperfusion of ischemic tissue is associated with the formation of hydroxyl radical (OH.). In this report, a novel mechanism for (OH.) generation from (1O2) is proposed based on the experimental evidence from the present study. A number of experiments were performed which conclusively demonstrated the formation of 1O2 from the reaction of lactic acid and hypohalite radical. Singlet oxygen attacks the unsaturated olefinic derivatives, which are also formed during reperfusion of ischemic tissue. The reaction between 1O2 and olefinic compounds produces hydroperoxides, which ultimately form OH. radical. The validity of the above mechanism of OH. radical formation is warranted from our experimental results.

Alkenes↗