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Biomedical subjects

Y Shukla

Publications and source records attributed to Y Shukla.

At least 19 recordsLinked to original sources
PubMed2006

Neuroprotective and neurorescue effect of black tea extract in 6-hydroxydopamine-lesioned rat model of Parkinson's disease.

In the present study, an attempt has been made to explore the neuroprotective and neuroreparative (neurorescue) effect of black tea extract (BTE) in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD). In the neuroprotective (BTE + 6-OHDA) and neurorescue (6-OHDA + BTE) experiments, the rats were given 1.5% BTE orally prior to and after intrastriatal 6-OHDA lesion respectively. A significant recovery in d-amphetamine induced circling behavior (stereotypy), spontaneous locomotor activity, dopamine (DA)-D2 receptor binding, striatal DA and 3-4 dihydroxy phenyl acetic acid (DOPAC) level, nigral glutathione level, lipid peroxidation, striatal superoxide dismutase and catalase activity, antiapoptotic and proapoptotic protein level was evident in BTE + 6-OHDA and 6-OHDA + BTE groups, as compared to lesioned animals. BTE treatment, either before or after 6-OHDA administration protected the dopaminergic neurons, as evident by significantly higher number of surviving tyrosine hydroxylase immunoreactive (TH-ir) neurons, increased TH protein level and TH mRNA expression in substantia nigra. However, the degree of improvement in motor and neurochemical deficits was more prominent in rats receiving BTE before 6-OHDA. Results suggest that BTE exerts both neuroprotective and neurorescue effects against 6-OHDA-induced degeneration of the nigrostriatal dopaminergic system, suggesting that possibly daily intake of BTE may slow down the PD progression as well as delay the onset of neurodegenerative processes in PD.

Animals↗
PubMed2005

Involvement of nitric oxide in neurodegeneration: a study on the experimental models of Parkinson's disease.

The present study was undertaken to explore involvement of nitric oxide (NO) in the experimental models of Parkinson's disease. Neurodegeneration was induced by unilateral injections of 6-hydroxydopamine (6-OHDA) or lipopolysaccharide (LPS) in the right striatum. Lesions were functionally evaluated by amphetamine-induced asymmetrical behaviour and by decrease in the tyrosine hydroxylase (TH) immunostaining. An induction in the expression of iNOS and augmentation in nitrite content was observed in both the models. The extent of increase in iNOS expression was, however, different but the elevation in the nitrite content was comparable in both the models. The increase in iNOS expression inversely correlated with the tyrosine hydroxylase (TH) immunolabeling. Animals pretreated with a NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), exhibited complete protection against amphetamine induced rotations in both the models. Thus, augmented NO availability subsequent to iNOS induction seems to play an important role in the initial phase of neurodegeneration.

Animals↗
PubMed2004

Modulation of altered hepatic foci induction by diallyl sulphide in Wistar rats.

Diallyl sulphide (DAS) is a sulphur-containing volatile compound present in garlic (Allium sativum). It has been shown to inhibit a number of chemically induced forms of cancer in experimental animals. The present study demonstrates the inhibitory effect of DAS on the development of diethylnitrosamine (DEN) initiated and 2-acetyl-aminofluorene (2-AAF) promoted preneoplastic altered hepatic foci (AHF) in Wistar rats. AHF were scored and analysed by quantitative stereology using the Image Analysis system from frozen liver sections stained for biological markers, namely glutathione S-transferase, placental form (GST-P), gamma-glutamyl transpeptidase (GGT), adenosine triphosphatase (ATPase), glucose-6-phosphatase (G6 Pase) and alkaline phosphatase (AlkPase). DAS-supplemented rats were found to restore the near-normal levels of enzymes GST-P and GGT when exposed to DEN and 2-AAF. DAS administration following DEN and 2-AAF exposure led to the restoration of enzymic activity of ATPase, G6 Pase and AlkPase, as evident by number and area of the foci. These findings suggest the protective role of DAS in rat hepatocarcinogenesis, by suppressing DEN- and 2-AAF-induced AHF development.

Allyl Compounds↗
PubMed2004

Co-transplantation of carotid body and ventral mesencephalic cells as an alternative approach towards functional restoration in 6-hydroxydopamine-lesioned rats: implications for Parkinson's disease.

Exogenous administration of various neurotrophic factors has been shown to protect neurons in animal model of Parkinson's disease (PD). Several attempts are being made to search a tissue source simultaneously expressing many of these neurotrophic factors. Carotid body (CB) contains oxygen-sensitive glomus cells rich in dopamine (DA) and expresses glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor and neurotrophin-3. We have attempted to study the functional restoration following co-transplantation of CB cells and ventral mesencephalic cells (VMC) in a 6-hydroxydopamine-lesioned rat model of PD. A significant recovery (p < 0.001) in d-amphetamine-induced circling behavior (80%) and spontaneous locomotor activity (85%) was evident in co-transplanted animals at 12 weeks post-transplantation as compared to lesioned animals. Similarly, a significant (p < 0.001) restoration was observed in DA-D(2) receptor binding (77%), striatal DA (87%) and 3,4-dihydroxyphenylacetic acid (DOPAC) (85%) levels and nigral DA (75%) and DOPAC (74%) levels. Functional recovery was accompanied by tyrosine hydroxylase (TH) expression and quantification of TH-positive cells by image analysis revealed a significant restoration in TH-immunoreactive (IR) fiber density in striatum, as well as TH-IR neurons in substantia nigra pars compacta in co-transplanted animals over VMC-transplanted animals. The result suggests that co-transplantation of CB cells along with VMC provides better and long-term functional restoration in the rat model of PD, possibly by supporting the survival of newly grafted cells as well as remaining host DA neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2003

Effect of glial cell line-derived neurotrophic factor (GDNF) co-transplantation with fetal ventral mesencephalic cells (VMC) on functional restoration in 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease: neurobehavioral, neurochemical and immunohistochemical studies.

Among trophic factors already known, glial cell line-derived neurotrophic factor (GDNF) and other members of its family have potent and specific action on dopaminergic neurons. In the present investigation an attempt has been made to validate the role of GDNF co-transplantation with fetal ventral mesencephalic cells (VMC) on functional viability and restoration using neurobehavioral, neurochemical and immunohistochemical parameters at 6 weeks post-transplantation in 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease (PD). A significant restoration (P<0.01) in D-amphetamine induced rotations, spontaneous and apomorphine induced locomotor activity in rats co-transplanted with VMC and GDNF was observed as compared to VMC alone transplanted rats. Level of dopamine (DA), 3,4-dihydroxy-phenyl acetic acid (DOPAC) and dopamine D2 (DA-D2) receptors in the caudate putamen (CPu) were significantly (P<0.001) restored in co-transplanted group as compared to VMC transplanted or GDNF administered animals. The functional viability of transplanted VMC was confirmed by tyrosine hydroxylase (TH) expression and quantification of TH-positive cells by image analysis revealed a significant restoration in TH-IR fibers density as well as TH-IR neurons counts in co-transplanted animals over VMC transplanted animals. Results suggest that co-transplantation of VMC and GDNF may be a better approach towards functional restoration in 6-OHDA lesioned rat model of Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2002

Induced expression of early response genes/oxidative injury in rat pheochromocytoma (PC12) cell line by 6-hydroxydopamine: implication for Parkinson's disease.

The expression of early response gene proteins c-Fos, c-Jun, and GAP-43 and their association with 6-hydroxydopamine (6-OHDA)-mediated oxidative injury were investigated using catecholaminergic PC12 cell line. Significant induction in the expression of c-Fos (P < 0.01), c-Jun (P < 0.001) and GAP-43 (P < 0.05) was observed following 2 h exposure to 6-OHDA (10(-6) M), which persisted during 24 h of observation. The exposed cells exhibited an increase in lipid peroxidation (48, 59 and 33%) along with decreased catalase activity (49, 30 and 13%) and glutathione levels (39, 28 and 16%) following 24, 48 and 72 h exposure, respectively. A concentration-dependent functional impairment of mitochondria as studied by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and decreased cell survival were also observed following 6-OHDA (10(-4), 10(-5) M) exposure for 24, 48 and 72 h. The results indicate a role of the early response gene in oxidative stress-mediated dopaminergic cell death by 6-OHDA. Similar mechanisms may also be operative in the development of Parkinson's disease, as an increased presence/formation of endogenous 6-OHDA has been reported in Parkinson's patients.

Animals↗
PubMed2001

Antimutagenic effect of black tea extract using 'rodent dominant lethal mutation assay'.

The antimutagenic effect of black tea extract has been evaluated with the 'Dominant Lethal Assay' in Swiss albino mice using benzo[a]pyrene [BaP] as a mutagen. BaP was given through the intraperitoneal (i.p.) route at a single dose of 100 mg/kg b.w. to male mice once only. The animals were given 1, 2 and 4% aqueous solution of black tea as sole source of drinking solution prior to BaP. The pregnant females were analyzed for living implants, pre- and post-implantation losses. The results revealed that during mating weeks, BaP caused a reduction in implants and an increase in pre- and post-implantation losses. The protective effect of tea solution on BaP-induced mutagenicity was observed. The number of living implants increased and dead implants decreased significantly in the animals kept on 2 and 4% tea solution. The increase in dominant lethal mutation rate by BaP was inhibited by black tea extract. Four percent tea solution alone did not produce dominant lethality, and reveals that it is non-toxic/non-mutagenic to sperm. Hence the study suggests that tea has a protective effect against BaP-induced genetic damage to germ cells in Swiss albino mice.

Animals↗
PubMed2001

Tumourigenic studies on deltamethrin in Swiss albino mice.

Deltamethrin, an alpha-cyano type II synthetic pyrethroid insecticide is used to control a wide range of insects on a variety of crops. Deltamethrin is reported to cause many adverse effects on non-target species. Deltamethrin is reported to cause DNA damage and micronuclei induction in human lymphocytes. It is highly toxic for other organisms such as aquatic invertebrates, fish and Daphnia. About the tumorigenic risk (both tumour initiating and promoting) associated with deltamethrin exposure, very few reports are available in literature. In the present set of investigations, deltamethrin has been evaluated for its tumorigenic and co-carcinogenic (tumour initiating and tumour promoting) potential following long term dermal exposure in Swiss albino mice. The results revealed that deltamethrin has only tumour initiating potential in both the sexes of Swiss albino mice, initiated with deltamethrin and promoted by standard tumour promoter, 12-O-tetra decanoyl phorbol-13-acetate (TPA). In the single dose initiated mice (deltamethrin 4 mg/kg body weight, once only), 44% males and 43% females developed benign skin tumours. A much higher incidence of tumorigenesis was recorded in multiple dose initiated animals (deltamethrin 4 mg/kg body weight, three times per week for 3 weeks), where 71% male and 75% female mice developed tumours at the site of application of deltamethrin. Deltamethrin exposure failed to show any tumour promoting and complete tumorigenic potential at all the three tested dose levels.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Neurodevelopmental consequences of gestational exposure (GD14-GD20) to low dose deltamethrin in rats.

Effect of low level in utero exposure to deltamethrin (DT) (1mg /kg wt.) during gestation day 14-20 was studied on selected neurobehavioral, neurochemical, immunohistochemical parameters in rats at 6 and 12 weeks postnatal period. The significant increase in acetylcholinesterase activity and decrease in (3)H-quinuclidinyl benzilate binding in the hippocampal region of DT exposed animals, suggesting impairment in cholinergic (muscarinic) receptors. A significant decrease in the learning and memory performances was also observed both at 6 and 12 weeks, which is directly correlated with decrease in muscarinic receptor binding. Immunohistochemistry and image analysis of growth associated protein-43, a neuron specific protein present in axonal growth cone and a marker for neuronal differentiation and synaptogenesis, exhibit aberrant increase in its expression in the hippocampus in DT exposed rats at both time periods. The data suggests that low level exposure to DT in utero during brain growth spurt period adversely affects the developing brain and the changes persist even up to 12 weeks postnatal period in rats. Although there is no significant recovery at 12 weeks assessment but still significant impairment persist on biochemical and behavioural parameters.

Acetylcholinesterase↗
PubMed2001

Transplacental carcinogenic potential of the carbamate fungicide mancozeb.

We evaluated the effects of mancozeb (Dithane M4-5), a protective carbamate fungicide, on transplacental carcinogenesis in Swiss albino mice. Mancozeb, a polymeric complex of ethylene bis (dithiocarbamate) manganese with zinc salt, is reported to possess carcinogenic and cocarcinogenic activity in various tumor models. In the present study, pregnant Swiss albino mice were administered mancozeb intraperitoneally on the 14th day of gestation. The first filial generation (F1 progeny) was promoted with a well-known tumor promoter 12-o-tetradecanoyl phorbol-13-acetate (TPA). The results revealed a significantly high tumor incidence (72%) in the F1 progeny of the animals initiated with mancozeb or a well known carcinogen 7,12-dimethyl benzanthracene (DMBA) and promoted with TPA in comparison to animals that were either from mothers given only the vehicle (DMSO) and promoted with TPA in F1 progeny or not promoted with TPA in F1 progeny. No significantly higher tumor incidence was observed in any other experimental groups. These results suggest that mancozeb or its metabolites are capable of crossing the placental barrier and can exert DNA damage and tumor initiating consequences in the fetal cells that, after promotion with TPA, get converted into neoplastic cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Histochemical localization of glutathione dependent NBT-reductase in mouse skin.

OBJECTIVE: Localization of the glutathione dependent Nitroblue tetrazolium (NBT) reductase in fresh frozen sections of mouse skin and possible dependence of NBT reductase on tissue thiol levels has been investigated. METHODS: The fresh frozen tissue sections (8 m thickness) were prepared and incubated in medium containing NBT, reduced glutathione (GSH) and phosphate buffer. The staining for GSH was performed with mercury orange. RESULTS: The activity of the NBT-reductase in mouse skin has been found to be localized in the areas rich in glutathione and actively proliferating area of the skin. CONCLUSION: The activity of the NBT-reductase seems to be dependent on the glutathione contents.

Animals↗
PubMed2000

Mutagenic evaluation of deltamethrin using rodent dominant lethal assay.

The dominant lethal test was used to analyse the mutagenic potential of deltamethrin, a synthetic pyrethroid insecticide, in Swiss albino mice. In the treated series, the animals were exposed orally to three different doses (0.36, 0.72 and 1.08 mg/kg body weight) of deltamethrin dissolved in corn oil. Following the treatment, each male of control, as well as of the treated series, was mated with untreated females, every week for a period of 6 weeks. All mated females were sacrificed on the 13th day of separation and their ovaries and uterus were examined. The results revealed that deltamethrin treatment did not impair the mating capacity and fertility of Swiss albino mice. Mutagenic index, pre- and post-implantation losses were assessed. No significant pre-implantation losses were observed either weekly or averagely. Post-implantation losses were observed at medium and high doses of deltamethrin. A slight increase in dominant lethal mutation rate was observed by increasing doses of deltamethrin in early weeks but decreased in later weeks, so an apparent dose response was not observed.

Administration, Oral↗
PubMed2000

Evaluation of carcinogenic and co-carcinogenic potential Quinalphos in mouse skin.

Quinalphos [O,O-diethyl-O-quinoxalinyl-phosphorothidate] is an organophosphorus pesticide with tremendous utility in mixed pest control due to its insecticidal and acaricidal properties. Apart from its pesticidal property, Quinalphos is known to induce various toxic effects in nontarget species and experimental animals. No studies have been conducted to evaluate the carcinogenic/co-carcinogenic hazards associated with Quinalphos exposure. In the present set of investigations, the tumorigenic potential of Quinalphos has been evaluated following topical exposure in Swiss albino mice. Long-term animal bioassays conducted for the evaluation of complete carcinogenic, tumour-initiating and tumour-promoting potential of Quinalphos revealed that it has only tumour-initiating potential at a dose of 10 mg/kg body weight (b.wt.), in the two-stage mouse skin model of carcinogenesis. Quinalphos exposure failed to produce neoplasia when tested for complete carcinogenic activity at all three tested dose levels or tumour promoting activity.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Effects of black tea extract on transplantable and solid tumors in Swiss albino mice.

The chemopreventive effects of green tea and its polyphenols are well documented in the literature. Epidemiological studies have suggested that green tea consumption might be effective in the prevention of certain human cancers. About 80% of the tea is consumed as black tea. Limited studies have been carried out to assess the usefulness of black tea as anti-carcinogen. The present set of investigations were initiated to study the anti-tumorigenic potential of aqueous black tea extract (ATE) in Swiss albino mice in in vivo animal bioassay, using 7, 12 dimethyl-benzanthracene (DMBA) as carcinogen. In the experimental group, 2% ATE was given orally as sole source of drinking water, while the control were allowed to drink normal water, ad lib. The results revealed that drinking of 2% ATE could effectively inhibit the onset of tumorigenesis, cumulative number of tumors and average number of tumors per mouse. In ATE drinking group 44% animals remained tumor free till the termination of experiment, i.e. 26 weeks. In the second set of experiment the preventive efficacy of 2% ATE of different cultivars of black tea, viz orthodox, CTC and dust were tested in Ehrlich Ascites (EA) tumor bearing mice. The preventive effects of ATE were observed in terms of increased life span (ILS). All the cultivars of tea showed more than 25% increase in life span of the animals. Cytotoxic effect of various doses of all three cultivars of black tea was also observed in vitro on EA cells.

Animals↗
PubMed1999

Inhibition of carcinogen induced activity of gamma-glutamyl transpeptidase by certain dietary constituents in mouse skin.

Cancer chemoprevention, a desirable and important facet of biomedical research, provides a practical approach to identify potentially useful inhibitors of cancer development, and offers an opportunity to study the mechanism of carcinogenesis. During the recent past a number of compounds have been tested for their anticarcinogenic potential specially constituents of our diet. The enzyme gamma-glutamyl transpeptidase (GGT) which catalyses the transfer of glutamyl groups of peptides to other peptides and amino acid and has been proposed as a marker of cell proliferation and neoplasia. It also serves as a tool to evaluate the carcinogenic and cocarcinogenic potential of environmental toxicants. In the present investigations, GGT activity induced by carcinogenic polycyclic aromatic hydrocarbons, viz. 7,12-dimethylbenz(a)anthracene (DMBA) and benzo(a) pyrene (BaP) was significantly inhibited by diallylsulfide (DAS) and indole-3-carbinol (I3C) in mouse skin. DAS and I3C are constituents of garlic and cruciferous vegetables respectively. A significant inhibition in GGT levels was also observed in a strong mitogen (12-o-tetradecanoyl phorbol-13-acetate) induced activity in mouse skin by pretreatment with DAS/I3C. Therefore these dietary constituents seem to be strong modifiers of chemically induced carcinogenesis.

Animals↗
PubMed1999

Inhibition of carcinogen-induced activity of gamma-glutamyl transpeptidase by certain dietary constituents in mouse skin.

Cancer chemoprevention, a desirable and important facet of biomedical research, provides a practical approach to identify potentially useful inhibitors of cancer development, and offers an opportunity to study the mechanism of carcinogenesis. During the recent past a number of compounds have been tested for their anticarcinogenic potential specially constituents of human diet. The enzyme gamma-glutamyl transpeptidase (GGT), which catalyses the transfer of glutamyl groups of peptides to other peptides and amino acids, has been proposed as a marker of cell proliferation and neoplasia. It also serves as a tool to evaluate the carcinogenic and cocarcinogenic potential of environmental toxicants. In the present investigations, GGT activity induced by carcinogenic polycyclic aromatic hydrocarbons, viz. 7,12-dimethyl-benz(a)anthracene (DMBA) and benzo(a)pyrene (BaP) was significantly inhibited by diallylsulfide (DAS) and indole-3-carbinol (I3C) in mouse skin. DAS and I3C are constituents of garlic. A significant inhibition in GGT levels was also observed in a strong mitogen (12-o-tetradecanoyl phorbol-13-acetate) induced activity by pretreatment of DAS/I3C in mouse skin. Therefore these dietary constituents seem to be strong modifiers of chemically induced carcinogenesis.

Allyl Compounds↗
PubMed1998

Antitumour promoting activity of indole-3-carbinol in mouse skin carcinogenesis.

There has been growing interest in recent years in the potential of brassica vegetables (cabbage, cauliflower, brussels sprouts, etc.) as vectors for the introduction of anticarcinogenic compounds in the diet. Indole-3-carbinol, a major indole metabolite present in the cruciferous vegetables, has been found to inhibit various rodent tumours when administered prior to or during carcinogen exposure. In this study, the antitumour promoting potential of indole-3-carbinol was studied in a two-stage mouse skin model of carcinogenesis. The animals were initiated with a single subcarcinogenic dose of DMBA. After one week, 250 microg of indole-3-carbinol was applied topically to each animal prior to promotion with 5 microg TPA twice per week. Tumour development was significantly inhibited in indole-3-carbinol-supplemented animals in terms of cumulative numbers of tumours and average tumours per mouse. About 44% of male and 29% of female mice remained tumour-free in this group at the end of the experiment. A significant delay in the tumour induction time was also observed in indole-3-carbinol-supplemented animals. This evidence suggests that indole-3-carbinol, in the manner and dose given, inhibits the development of tumours in the two-stage mouse skin model of carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗