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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
PubMed1994

Influence of combined deficiency of fat and vitamin A on benzo(a)pyrene-induced lung carcinogenesis in rats.

The present study shows the effect of combined dietary deprivation of fat and vitamin A on benzo(a)pyrene (BaP) induced lung carcinogenesis in male Wistar rats. Lung tumors were induced by intratracheal instillation of BaP-Fe2O3 in normal saline. The tumor incidence and tumor burden in control animals were 82% and 2.28 respectively. Fat deficiency decreased the tumor incidence to 57% and tumor burden to 1.66. On the other hand, in vitamin A deficiency these were 83% and 4.02 respectively. Fat deprivation in the diet of animals fed with vitamin A deficient diet decreased the tumor incidence and tumor burden to 69.6% and 2.7 respectively. The results suggest a protective role of low intake of fat in vitamin A deficiency for BaP-induced lung tumorigenesis in rats.

Animals↗
PubMed1993

Serum beta-N-acetylhexosaminidase, carcinoembryonic antigen & sialic acid in benign & malignant extrahepatic biliary obstruction.

Study of tumour markers to differentiate benign and malignant extra hepatic biliary obstructions showed that levels fo serum beta-N-acetylhexosaminidase and lipid associated sialic acid were not different in the two groups. The levels of carcinoembryonic antigen (CEA) and total sialic acid (TSA), on the other hand, were significantly higher in patients with the malignant biliary obstruction. At a cut-off value of 6.4 ng/ml (mean + 2SD) CEA had 66.7 per cent true positivity in malignancy 100 per cent true negativity in control and 78 per cent true negativity in the benign group. Similarly, TSA at a cut off value of 60 mg/dl had 61 per cent true positivity in malignancy, 90 per cent true negativity in controls and 70 per cent true negativity in the benign group. These two tumour markers appear to have similar diagnostic potential for malignant extrahepatic biliary obstruction. Surgical management of the malignant obstruction did not result in a decline in the elevated levels of these two markers during the post-surgical period of 7 days.

Bile Duct Neoplasms↗
PubMed1992

Effect of combined deficiency of fat and vitamin A on N-nitrosodiethylamine-induced lung carcinogenesis in mice.

The present investigation shows the effect of combined dietary deprivation of fat and vitamin A on N-nitrosodiethylamine (NDEA) induced lung carcinogenesis in male Swiss NMRI mice. Lung tumors were induced by three intragastric administrations of NDEA (80, 80, 40, mg/kg body wt.) in normal saline with a gap of 4 weeks between each administration. The tumor incidence and tumor burden in control animals were found to be 39.1 and 3.9%, respectively. Fat deficiency decreased the tumor incidence to 30.4% and tumor burden to 3.7%. On the other hand, vitamin A deficiency increased them to 95.6 and 6.8%, respectively. Fat deprivation in the diet of animals fed with vitamin A deficient diet decreased the tumor burden and tumor incidence to 59.0 and 4.0%, respectively which were still more than in the control animals. This study suggests a protective role for low intake of fat in vitamin A deficiency.

Animals↗
PubMed1991

Influence of ellagic acid on antioxidant defense system and lipid peroxidation in mice.

Addition of ellagic acid (EA) to liver microsomes of mice resulted in a steady increase in inhibition of NADPH-dependent lipid peroxidation up to 2 mM concentration. The maximum of 70% inhibition of ascorbate-dependent lipid peroxidation was achieved at 1 mM concentration of EA. Feeding of EA significantly increased the levels of reduced glutathione and glutathione reductase in liver and lungs of male and female mice. However, there were no changes in the activities of catalase and superoxide dismutase. On the other hand, microsomes from liver and lungs of EA fed animals showed significantly suppressed NADPH- and ascorbate-dependent lipid peroxidation.

Animals↗
PubMed1990

Effect of cigarette smoke inhalation on benzo[a]pyrene-induced lung carcinogenesis in vitamin A deficiency in the rat.

Vitamin A deficiency caused a significant increase (P less than 0.05) in benzo[a]pyrene (BP)-induced lung tumor incidence and tumor burden in male Wistar rats. Inhalation of cigarette smoke during initiation and post-initiation phases of carcinogenesis resulted in higher tumor burden as compared to the same observed in the animals exposed to cigarette smoke during the post-initiation phase only. Stimulation in tumor burden by cigarette smoke was increased further by vitamin A deficiency.

Administration, Inhalation↗
PubMed1990

Differential effects of fat deficiency on hepatic and pulmonary drug metabolizing enzymes in rat and mouse.

In the present study, we have evaluated the effect of dietary fat deprivation on the carcinogen/drug metabolizing enzymes in rats and mice. In rats, hepatic AHH, Cyt.P-450 Cyt.b5 and Cyt.c-reductase were significantly decreased due to fat deficiency, whereas in lungs, AHH and Cyt.c-reductase were decreased without any change in Cyt.P-450 level. In mice, feeding of fat-free diet did not cause any alteration in hepatic AHH and Cyt.P-450, but the levels of Cyt.b5 and Cyt.c-reductase were significantly reduced. In contrast to liver, Cyt.P-450 and Cyt.b5 were increased in lungs. Activity of UDPGT was lowered both in liver and lungs of rats whereas GST and GSH were increased in liver only. In mice, a decrease in UDPGT and appreciable increases in GST and GSH in liver were observed. However, in lungs, UDPGT activity was enhanced by feeding fat-free diet. These observations suggest that mice and rats respond differentially to the depletion of fat in the diet.

Animals↗
PubMed1990

Inhibition of arylhydrocarbon hydroxylase and cytochrome P-450 by 20-methylcholanthrene and phenobarbital in guinea pig on excessive doses of ascorbic acid.

Treatment of guinea pigs on adequate ascorbic acid (AA) with 20-methylcholanthrene (MCA) and phenobarbital (PB) significantly increased hepatic arylhydrocarbon hydroxylase (AHH), cytochrome P-450 and cytochrome-b5 activities. In lungs, only MCA treatment significantly enhanced the activities of AHH, cytochrome P-450 and cytochrome b5. In animals on excessive doses of AA, there was inhibition of hepatic AHH, cytochrome P-450 and cytochrome b5 levels by treatment with these xenobiotics. Also, inhibition was observed in pulmonary AHH and cytochrome P-450 levels. The relevance of these observations in excessive AA-fed guinea pigs to carcinogenesis requires further extensive investigations.

Animals↗
PubMed1988

Effect of cigarette smoke inhalation on antioxidant enzymes and lipid peroxidation in the rat.

Inhalation of cigarette smoke significantly increased glutathione (GSH) content and increased lipid peroxidation without altering the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) or glutathione reductase (GR) in the lung (six male Wistar rats). Following intratracheal administration of benzo[a]pyrene (BP), an increase in pulmonary GSH-Px activity, GSH content and lipid peroxidation was observed after 12 h. GSH-Px activity and GSH content returned to control values by 7 and 30 days, respectively, whereas lipid peroxidation in the lung remained significantly greater than the control value for up to 7 days of BP administration. Hepatic activity of SOD was increased significantly, whereas the activities of GSH-Px, catalase, GR, and GSH content were not changed by inhalation of cigarette smoke. On administration of BP, a significant increase in the activities of SOD and GSH-Px was observed at 12 h. After 7 and 30 days, the activities of these antioxidant enzymes were comparable to their respective control group values. No change in the activity of catalase or in the level of lipid peroxidation was noted throughout the entire study period.

Administration, Inhalation↗
PubMed1987

Effect of excessive intake of ascorbic acid on hepatic and extra-hepatic phase I and phase II drug metabolism in rat.

Guinea pig is the animal model of choice for studies on effects of ascorbic acid (AA). However, rat is one of the largely used animals for investigations related to chemical carcinogenesis. Therefore, the present study was designed to evaluate the changes induced by high intake of the vitamin in xenobiotic and carcinogen metabolizing status of the organs. Male Wistar rats, dosed daily with 50 mg AA/100 g body weight for 10 weeks, demonstrated a small non-significant increase in hepatic, pulmonary and colon cytochrome P-450 (Cyt. P-450) contents, which was accompanied with a significant increase in hepatic and pulmonary arylhydrocarbon hydroxylase (AHH) activities. Phase II enzymes of drug metabolism responded in different ways to increased intake of AA. UDP-glucuronyltransferase (UDPGT) activity was unaffected in liver and colon, but it was increased (p less than 0.005) in lung. Activities of glutathione S-transferase (GST) were decreased in the three organs. Inducibility of AHH by 3-methylcholanthrene (MCA) or phenobarbital (PB) was largely reduced due to AA feeding. Besides this, MCA and PB had differential effects on enzymatic levels in AA fed rats. When compared with our earlier observations in guinea pig, it was found that rat responded similarly to guinea pig to increased intake of AA with regard to hepatic AHH, Cyt. P-450, UDPGT and GST, pulmonary AHH, Cyt. P-450 and Cyt. b5, and all studied colon enzymes, except GST.

Animals↗
PubMed1986

Effect of large doses of ascorbic acid on the hepatic and extra-hepatic drug-metabolizing enzymes in guinea pig.

Water solubility and non-toxic properties of ascorbic acid are taken as criteria for beneficial effects of large doses of the vitamin. In the present study, male guinea pigs, dosed daily with 15, 30 or 50 mg/100g body weight for 10 weeks, demonstrated no differences in effect on liver and lung weights, body growth and microsomal protein contents of liver and lung when compared with controls. When guinea pigs were fed excessive ascorbic acid, there was a small non-significant increase (p less than 0.05) in hepatic and pulmonary cytochrome P-450, and significant increase (p less than 0.05) in hepatic cytochrome b5 which was accompanied with a significant increase in arylhydrocarbon hydroxylase activity in the two organs. Activity of NADPH-dependent cytochrome c-reductase was decreased in liver and remained unaffected in lung and colon. Drug detoxifying enzymes responded in different ways to increased intake of ascorbic acid. Activity of UDP-glucuronyltransferase remained unchanged on feeding excessive ascorbic acid, whereas glutathione S-transferase was decreased significantly in liver and was unaltered in lung and colon. Reduced glutathione was decreased only in the lung. The observed changes in drug activating and detoxifying enzymes appear to be important from drug pharmacokinetics and carcinogenesis point of view.

Animals↗
PubMed1985

The effect of medroxyprogesterone acetate on the hepatic drug-metabolizing enzymes in normal and protein-deficient female rats.

Effect of depot medroxyprogesterone acetate on the hepatic drug-metabolizing enzymes was studied in female protein-deficient and normal pair-fed rats. Treatment with this drug did not cause any change in organ weight, microsomal protein, and soluble protein yield per gram of tissue in both groups. MPA administration resulted in significant increases in the content of cytochrome P-450 and b5, and activities of benzo[a]pyrene hydroxylase, UDP-glucuronosyltransferase, and NADPH-Cyt c reductase in both pair-fed control and protein-deficient rats. However, the content of glutathione and activity of glutathione-S-transferase were not affected appreciably. The present study suggests that MPA treatment induces drug-metabolizing enzymes in liver to almost the same extent in both protein-deficient and normal pair-fed rats.

Animals↗
PubMed1985

The effect of vitamin A deficiency on the initiation and postinitiation phases of benzo(a)pyrene-induced lung tumourigenesis in rats.

The present investigation shows the effect of vitamin A deficiency on the initiation and postinitiation phases of benzo(a)pyrene-induced lung carcinogenesis in male Wistar rats. Lung tumours were induced by giving three intratracheal instillations, one week apart, of 10 mg benzo(a)pyrene per instillation. Maximum tumour incidence (100%) and tumour burden per rat was found in rats which were kept on vitamin A deficient diet for 4 weeks prior to the first administration and 8 weeks after the last administration of benzo(a)pyrene. Rats in which vitamin A deficiency was terminated after the last administration of the carcinogen had 83% tumour incidence, whereas corresponding control pairfed animals had 39% incidence of tumours. These data represent the values obtained 32 weeks after the last administered dose of the carcinogen and indicate the role of vitamin A, both in the initiation as well as in the postinitiation phases of lung carcinogenesis.

Animals↗
PubMed1985

Effect of vitamin A deficiency on pulmonary and hepatic in vitro metabolism of benzo(a)pyrene in rat.

The metabolism of (3H)-benzo(a)pyrene and the activities of enzymes involved in its metabolism were studied in rat lung and liver in vitamin A deficiency. Deficiency of vitamin A resulted a significant decrease in the overall metabolism of benzo(a)pyrene in the liver in vitro, whereas no significant difference was evident in the lung. The ethyl acetate-soluble metabolites of benzo(a)pyrene formed by lung and liver preparations were unaltered qualitatively by vitamin A deficiency. However, quantitative analysis revealed that vitamin A deficiency decreased the yield of dihydrodiols, quinones and phenols in liver, and dihydrodiols in lung. The hepatic cytochrome P-450 content, arylhydrocarbon hydroxylase and uridine diphosphate-glucuronosyl transferase activities were reduced, whereas glutathione S-transferase activity was increased in the vitamin A deficient animals. Contrary to this, pulmonary cytochrome P-450 content was above the control values (p less than 0.01) and no alteration in pulmonary arylhydrocarbon hydroxylase activity was observed in vitamin A deficient rats. Uridine diphosphate-glucuronosyltransferase and glutathione S-transferase activities were impaired in lung by inducing vitamin A deficiency. However, no significant difference was evident in the overall metabolism of benzo(a)pyrene by lung supernatants from the two groups.

Animals↗