Biomedical subjects

C Dwivedi

Publications and source records attributed to C Dwivedi.

At least 19 recordsLinked to original sources

PubMed1999

Antitumor drug delivery by tissue electroporation.

Tissue electroporation has been explored to enhance the local delivery of chemotherapueutic agents to solid tumors. The technique, known as electrochemotherapy (ECT), uses high-voltage pulses to deliver drugs across cancerous tissues. ECT has been demonstrated to be an effective treatment for cutaneous malignancies. Recent studies also indicate that the applications of ECT can be extended from the treatment of cutaneous cancers to the treatment of tumors of vital organs such as brain, liver, lungs and others. This review also discusses electrogene antitumor therapy.

Animals↗

PubMed1999

Sandalwood oil prevent skin tumour development in CD1 mice.

Sandalwood oil (SW oil) has been used for the treatment of inflammatory and eruptive skin diseases. In the present study, the chemopreventive effects of SW oil on 7,12-dimethylbenz(a)-anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol-13-acetate(TPA)-promoted skin tumour development and TPA-induced ornithine decarboxylase (ODC) activity in CD1 mice were investigated. Female CD1 mice (5-6 weeks old) were divided in different groups, having 30 mice in each group. One week after topical application of DMBA (200 nmole in 100 microl acetone) alone or with SW oil at different concentrations (100 microl, 1.25, 2.5, 3.75, 5% in acetone), at different times (0.5, 1, 2 h) before DMBA, the mice were treated topically with TPA (5 nmole in 100 microl acetone) alone or with SW oil at different concentrations (100 microl, 1.25, 2.5, 3.75, 5% in acetone) at different times (0.5, 1, 2 h) before TPA applications twice a week for 20 weeks. The mice were weighed and papillomas counted weekly. The results indicate that SW oil pre-treatment decreased the papilloma incidence and multiplicity in a concentration and time-dependent manner. The pre-treatment with 5% SW oil (100 microl) 1 h before DMBA and TPA treatments provided a maximum of 67% and 96% decrease in papilloma incidence and multiplicity, respectively, after 20 weeks of promotion. The mice pre-treated with SW oil at all concentrations and time period before TPA had significantly lower ODC activity than the group treated with TPA alone. The data suggest that SW oil could be an effective chemopreventive agent against chemically-induced skin cancer.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1998

Effects of oil-soluble organosulfur compounds from garlic on doxorubicin-induced lipid peroxidation.

Clinical efficacy of doxorubicin is compromised due to free radical generation leading to cardiac toxicity. Oil-soluble organosulfur compounds, diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS), present in garlic were examined for their antiperoxidant effects. DADS inhibited liver microsomal lipid peroxidation induced by NADPH, ascorbate and doxorubicin. DAS, DPS and DPDS were ineffective inhibitors of liver microsomal lipid peroxidation. DADS could be used in combination with doxorubicin to protect oxidative injuries to improve the clinical efficacy of doxorubicin.

Allyl Compounds↗

PubMed1997

Chemopreventive effects of sandalwood oil on skin papillomas in mice.

The essential oil, emulsion or paste of sandalwood (Santalum album L) has been used in India as an ayurvedic medicinal agent for the treatment of inflammatory and eruptive skin diseases. In this investigation, the chemopreventive effects of sandalwood oil (5% in acetone, w/v) on 7,12-dimethylbenz(a)anthracene-(DMBA)-initiated and 12-O-tetradecanoyl phorbol-13-acetate(TPA)-promoted skin papillomas, and TPA-induced ornithine decarboxylase (ODC) activity in CD1 mice were studied. Sandalwood oil treatment significantly decreased papilloma incidence by 67%, multiplicity by 96%, and TPA-induced ODC activity by 70%. This oil could be an effective chemopreventive agent against skin cancer.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1996

Effects of diallyl sulfide and diallyl disulfide on cisplatin-induced changes in glutathione and glutathione-S-transferase activity.

The effects of diallyl sulfide (DAS) and diallyl disulfide (DADS) on cisplatin-induced changes in glutathione (GSH) and glutathione-S-transferase (GST) activity in rat liver and kidney was investigated. Cisplatin treatment significantly (p < 0.05) decreased GSH and GST activity in both liver and kidney. DADS treatment significantly (p < 0.05) enhanced GSH and GST activity in rat liver and kidney. Furthermore, DADS treatment reversed the effect of cisplatin on GSH and GST activity both in liver and kidney. Administration of DADS with cisplatin could enhance GSH and GST activity and lower cisplatin-induced nephrotoxicity.

Allyl Compounds↗

PubMed1996

Aluminum polymeric implants: in vitro-in vivo evaluations.

The purpose of this investigation is to study the effect of long-term subcutaneous aluminum polymeric implants on aluminum release and accumulation in various tissues in rats. The implants were formulated using silicone rubber and polyurethane polymers and three different aluminum salts. The polymeric matrices were evaluated for in vitro release studies. These matrices released aluminum in vitro up to the period of four months. The aluminum matrices were implanted in rats and animals were sacrificed at various time intervals. Various tissues such as brain, kidney, liver, intestine, and heart were isolated. Aluminum in dried tissues was analyzed by Neutron Activation Analysis. Results from this investigation suggest that polymeric aluminum implants raise the aluminum concentration in the brain and liver. However, these implants did not increase aluminum levels in intestine, heart, and kidney. The polymeric aluminum implants could be used to establish an animal model for the neuropathology of dementia.

Aluminum↗

PubMed1996

Biodistribution of cocaine during perinatal period in rats.

Differences in cocaine-induced central nervous system toxicity in pregnant and postpartum rats have been observed. For example, a 20 mg/kg, intraperitoneal dosage of cocaine that was tolerated during pregnancy caused tonic-clonic convulsions and death during the postpartum period. In the present study, biodistribution of cocaine during different perinatal periods was investigated to understand the differences in toxicity. Nonpregnant, 22-day pregnant, and postpartum rats were injected with 3H cocaine (12 mg/20 mu ci/kg, i.v.). Rats were sacrificed under ether anesthesia at predetermined time intervals. Brain, serum, fetal brain and placenta (from pregnant rats) samples were isolated, solubilized, and counted in a scintillation counter for radioactivity. Peak levels of cocaine were observed at 15 and 60 minutes after injection in maternal serum and brain, respectively, in 22-day pregnant rats. However, peak levels of cocaine were observed at 30 minutes after the injection in placental and fetal brain tissues from 22-day pregnant rats. Cocaine level of brain was elevated in all postpartum rats compared to nonpregnant and pregnant rats. These results indicated that higher levels of cocaine is distributed to brain after delivery compared to the nonpregnant and pregnant rats which may explain increased CNS toxicity during postnatal period.

Animals↗

PubMed1995

Selenium detoxification by methylation.

The major detoxification process for selenium is methylation. The major pathway for the formation of methylated compounds in biological systems is transmethylation catalyzed by methyltransferases. In this study methyltransferase activity was assayed in the liver cytosol prepared from different strains of rats using HPLC method by measuring the formation of epinephrine from norepinephrine. The methyltransferase activity in Fischer, Wistar, and Sprague-Dawley rats were 1.65 x 10(-12), 0.74 x 10(-12), and 1.2 x 10(-12) moles epinephrine formed/mg protein/hr respectively. Volatilization of injected Se (2.5 mg/kg, i.p.) was found to be higher in Wistar rats compared to Fischer rats. LD50 for Wistar and Fischer rats were 2.58 and 3.15 mg Se/kg respectively. Our results suggest that the methylation of dimethyl selenide to trimethhyl selenide appears to be an important step in the detoxification of selenium.

Animals↗

PubMed1994

Modulation of 12-0-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity by calcium and verapamil in mouse.

Calcium has been suggested to be an intracellular second messenger for ornithine decarboxylase (ODC) induction caused by 12-O-tetradecanoylphorbol-13-acetate (TPA). In the present study, the effects of dietary calcium supplement and calcium and verapamil injections on TPA-induced ODC activity in skin was investigated in CD-1 and SENCAR mouse. Dietary calcium supplement did not influence ODC induction caused by TPA. However, calcium injections enhanced the TPA-induced ODC activity in CD-1 and SENCAR mouse skin. Verapamil injections resulted in a significant decrease in TPA-induced ODC activity in CD-1 and SENCAR mice. These results suggest that calcium and calcium antagonists may play a role in skin tumor promotion caused by TPA.

Animals↗

PubMed1994

Effects of methoxychlor on skin tumor development.

Organochlorine pesticides increase the incidence of liver cancer through a multistage process involving tumor promotion. Mirex, an organochlorine pesticide has been shown to be a tumor promoter in mouse skin. In the present study, the effects of methoxychlor, a commonly used organochlorine pesticide, on the development of papillomas in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin and induction of mouse epidermal ornithine decarboxylase (ODC) activity were investigated and compared with 12-O-tetradecanoylphorbol-13-acetate (TPA), a well-known tumor promoter. Methoxychlor neither caused tumor development nor induced epidermal ODC activity. However, TPA resulted in 100% tumor incidence and 8.8 tumors per mouse after 20 weeks of promotion, and induced epidermal ODC activity.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1993

Alterations in biodistribution of cocaine may explain differential toxicity in pregnant and postpartum rats.

Biodistribution of cocaine in female rats before and after delivery of litters was studied in order to provide an explanation for the observed differences in cocaine-induced toxicity in pregnant and postpartum rats. Cocaine (20 mg/kg, ip) given to female rats at 16 days of gestation or 20 days of gestation did not have any apparent neurotoxic effects in the mothers. Similarly, no apparent toxicity was observed in virgin animals injected with the same dosage of cocaine. However, administration of the same dosage of cocaine to rats after delivery caused clonic-tonic convulsions and death within 5 min of injection. In an effort to explain these differences, the biodistribution of cocaine was investigated by injecting levo-[benzoyl-3,4-3H(N)] cocaine (20 mg/20 microCi/kg, ip) to nonpregnant rats and rats at different gestation periods and after delivery. The mean serum/brain ratios (concentration of cocaine in serum divided by cocaine concentration in the brain) of cocaine 5 min after injection in rats at 16 days gestation, 20 days gestation, within a 12-hr period after delivery, and in control virgin animals were 2099, 1132, 427, and 632, respectively. These results indicate that the biodistribution of cocaine is altered at parturition. This may explain the increased central nervous system toxicity in rats treated with cocaine after delivery. Results from this investigation may be useful in evaluating complications during labor and delivery which have been associated with cocaine abuse by pregnant women.

Animals↗

PubMed1992

Effects of verapamil on the acute toxicity of doxorubicin in vivo.

BACKGROUND: Studies indicating that verapamil substantially enhances doxorubicin levels in certain drug-resistant tumor cells have led to the use of verapamil in combination with doxorubicin in animal and clinical studies of multidrug-resistant tumors. These studies have shown this drug combination to be associated with severe toxic effects. It is important to determine whether verapamil modulates the dose-limiting and potentially lethal cardiotoxicity of doxorubicin and to elucidate possible mechanisms. PURPOSE: The aims of this study were to evaluate the in vivo effects of verapamil on (a) doxorubicin-stimulated cardiac lipid peroxidation and cardiac damage, (b) doxorubicin-induced animal mortality, and (c) biodistribution of doxorubicin to the heart. METHODS: Male (BALB/c x DBA/2)F1 mice were treated with a high dose of doxorubicin (15 mg/kg, injected intraperitoneally), verapamil (25 mg/kg, injected intraperitoneally), or combinations of the two. Lipid peroxidation was determined using the 2-thiobarbituric acid assay for malonaldehyde. Light microscopy was used for histopathologic examination of cardiac tissue. A fluorometric assay procedure was employed to determine doxorubicin levels in the heart. RESULTS: Verapamil was an effective inhibitor of peroxidative damage to myocardial lipids following a high dose of doxorubicin (15 mg/kg, injected intraperitoneally). However, mice treated with verapamil and doxorubicin had a lower survival rate and a higher initial peak concentration of doxorubicin in the heart than those treated with doxorubicin alone. They also demonstrated a higher incidence and severity of degenerative changes in cardiac tissue. CONCLUSIONS: Our findings suggest that verapamil effectively inhibits doxorubicin-mediated lipid peroxidation in vivo but that cardiac lipid peroxidation is not the major limiting mechanism underlying doxorubicin-induced toxicity. A possible explanation for the excess mortality and cardiac injury in mice treated with verapamil plus doxorubicin is that verapamil alters the pharmacokinetics of doxorubicin. IMPLICATIONS: Further studies are necessary for development of safer protocols and/or drug combinations to treat multidrug-resistant tumors. We are currently studying treatment of tumor-bearing animals with a cumulative dosage regimen of doxorubicin in the presence and absence of verapamil.

Animals↗

PubMed1992

Dietary glucarate-mediated inhibition of initiation of diethylnitrosamine-induced hepatocarcinogenesis.

Previously, it has been reported that calcium glucarate is a potent inhibitor of chemical carcinogenesis, including phenobarbital-promoted diethylnitrosamine-initiated hepatic toxicity expressed as altered hepatic foci in rats. The purpose of the present study was to determine whether calcium glucarate could inhibit the immediate and delayed appearance of altered hepatic foci when fed to rats during the initiation phase of diethylnitrosamine-induced hepatocarcinogenesis. The effects of dietary mode of administration of calcium glucarate on the initiation phase of hepatocarcinogenesis were also examined. Since diethylnitrosamine is not known to undergo glucuronidation and calcium glucarate has been shown to enhance clearance of circulating estrogens, an indirect mechanism of action of calcium glucarate was also evaluated by pretreating rats with an anti-estrogen, tamoxifen, prior to partial hepatectomy and administration of diethylnitrosamine. Calcium glucarate significantly inhibited both the early and delayed appearance of altered hepatic foci and exerted maximal inhibition when administered by gavage prior to diethylnitrosamine. Maximal inhibition was obtained when calcium glucarate was provided continuously in the diet of animals up to 5 and 7 months. Pretreatment of animals with tamoxifen before partial hepatectomy and diethylnitrosamine resulted in maximal inhibition of the initiation phase of hepatocarcinogenesis. This suggests but does not prove that the anti-carcinogenic activity of calcium glucarate was due to decreased liver proliferation. In the present study, the proliferation of ductular epithelial and oval cells appeared to be associated with the administration of diethylnitrosamine. Collectively, our data suggest that calcium glucarate inhibited the initiation phase of diethylnitrosamine-induced hepatocarcinogenesis.

Animals↗

PubMed1992

Chemoprevention of chemically induced skin tumor development by diallyl sulfide and diallyl disulfide.

Garlic and onion oil have been shown to inhibit chemically induced skin tumor development in mice. In the present study, the effects of diallyl sulfide and diallyl disulfide, oil-soluble constituents of garlic and onion, on 7,12-dimethylbenz(a)anthracene-induced and 12,O-tetradecanoylphorbol-13-acetate-promoted skin tumor formation were examined in SENCAR mice. Topical application of diallyl sulfide or diallyl disulfide significantly inhibited skin papilloma formation from the ninth week of promotion and significantly increased the rate of survival in the murine model. Our findings support earlier evidence that these naturally occurring compounds may be useful for the chemoprevention of certain types of tumors.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1991

Inhibitory effects of Maharishi-4 and Maharishi-5 on microsomal lipid peroxidation.

The effects of Maharishi-4 (M-4) and Maharishi-5 (M-5) on microsomal lipid peroxidation were examined in vitro. Rat liver microsomes were incubated with an NADPH-generating system or with sodium ascorbate and an ADP-iron complex to stimulate enzymatic or nonenzymatic lipid peroxidation respectively. Alcoholic or aqueous extracts of M-4 or M-5, when added to these incubation systems, inhibited hepatic microsomal lipid peroxidation in a concentration-dependent manner. The aqueous extract of M-4 was the most effective antiperoxidant in these systems. A 10% (w/v) aqueous extract of M-4 inhibited ascorbate or NADPH-induced lipid peroxidation by approximately 50% when added at volumes of 8 microliters and 3.5 microliters respectively to the incubation mixtures (total incubation volume, 2 ml). These findings suggest that M-4 and M-5, by virtue of their antiperoxidant properties, may be useful in the treatment of free radical-linked drug toxicities and disease states.

Animals↗

PubMed1990

Plasma lipid-bound sialic acid alterations in neoplastic diseases.

Plasma lipid-bound sialic acid (LSA) was assayed in normal volunteers, patients with non-malignant diseases, and a variety of cancer patients. Mean plasma LSA in 50 normal volunteers, 16 patients with non-malignant diseases, 54 breast cancer, 17 lung cancer, 15 colon cancer, 7 ovarian cancer, 5 prostate cancer, 4 leukemia, 4 gastrointestinal, 3 thyroid cancer, 3 pancreas cancer and 2 adrenal cancer patients were 17.7, 23.2, 58, 85, 56.7, 46.2, 56.7, 53.3, 31.1, 33.2 and 119.5 mg/dl, respectively. None of the normal volunteers had elevated plasma LSA values. Plasma LSA level was not significantly different in male and female volunteers. Two out of 114 different cancer patients had plasma LSA levels within normal range exhibiting 98.2% sensitivity of the assay. Plasma LSA, which is relatively simple to assay, may be used as a tumor marker in wide variety of neoplastic diseases.

Adult↗

PubMed1990

Antineoplastic properties of Maharishi-4 against DMBA-induced mammary tumors in rats.

Maharishi-4 (M-4), an ayurvedic food supplement, was tested for anticarcinogenic and anticancer properties against 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats. The 6% M-4-supplemented diet protected DMBA-induced carcinogenesis by reducing both tumor incidence and multiplicity during initiation and promotion phases. The control animals who developed tumors when supplemented with M-4 diet for four weeks showed tumor regression in 60% of cases. There was no significant difference in the food intake or weight gain in rats who were on M-4-supplemented diet compared to control group. Possible mechanisms of action of M-4 are discussed.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1990

Effect of calcium glucarate on beta-glucuronidase activity and glucarate content of certain vegetables and fruits.

Glucarate is normally present in tissues and body fluids and is in equilibrium with D-glucaro-1,4-lactone, a natural inhibitor of beta-glucuronidase activity. Dietary calcium glucarate, a sustained-release from of glucarate, elevates the blood level of D-glucaro-1,4-lactone which suppresses blood and tissue beta-glucuronidase activity. A single dose of CaG (4.5 mmole/kg body weight) inhibited beta-glucuronidase activity in serum and liver, lung, and intestinal microsomes by 57, 44, 37, and 39%, respectively. A chronic administration of calcium glucarate (4% in diet) also decreased beta-glucuronidase activity in intestinal and liver microsomes. Maximal inhibition of beta-glucuronidase activity in serum was observed from 12 noon to 2:00 PM. In contrast, maximum inhibition of beta-glucuronidase activity in intestinal and liver microsomes occurred during mornings, although a secondary depression in intestinal microsomes also occurred around 4 PM. A 4% calcium glucarate supplemented diet also inhibited beta-glucuronidase activity by 70% and 54%, of the bacterial flora obtained from proximal (small intestine) and distal (colon) segments of intestine, respectively. Due to the potential effect of dietary glucarate on net glucuronidation and on other metabolic pathways, glucaric acid levels in various foods were determined. The glucaric acid content varied from a low of 1.12-1.73 mg/100 g for broccoli and potatoes to a high of 4.53 mg/100 g for oranges.

Animals↗