Biomedical subjects

T Shivanandappa

Publications and source records attributed to T Shivanandappa.

At least 19 recordsLinked to original sources

PubMed2006

Hepatoprotective effect of the aqueous extract of the roots of Decalepis hamiltonii against ethanol-induced oxidative stress in rats.

The hepatoprotective activity of the aqueous extract of the roots of Decalepis hamiltonii was investigated against ethanol-induced oxidative stress and liver damage. Pretreatment of rats with aqueous extract of the roots of D. hamiltonii, single (50, 100 and 200mg/kg b.w.) and multiple doses (50 and 100mg/kg b.w. for 7 days) significantly prevented the ethanol (5g/kg b.w.) induced increases in the activities of the serum enzymes, aspartate and alanine transaminases, alkaline phosphatase and lactate dehydrogenase in a dose dependent manner. Parallel to these changes, the root extract inhibited the ethanol-induced oxidative stress in the liver by suppressing lipid peroxidation and protein carbonylation and maintaining the levels of antioxidant enzymes and glutathione. The biochemical changes were consistent with histopathological observations suggesting marked hepatoprotective effect of the root extract. The protective effect of the root extract against hepatotoxicity of alcohol was more pronounced by the multiple dose pretreatment. Hepatoprotective activity of the aqueous extract of the roots of D. hamiltonii could be attributed to the antioxidant effect of the constituents and enhanced antioxidant defenses.

Journal Article↗

PubMed2006

Novel antioxidant compounds from the aqueous extract of the roots of Decalepis hamiltonii (Wight and Arn.) and their inhibitory effect on low-density lipoprotein oxidation.

Roots of Decalepis hamiltonii are consumed as pickles and as a health drink in southern India for their health benefits. The antioxidant properties of the root extracts have been shown previously; this paper reports the isolation of antioxidant compounds from the aqueous extract of the roots of D. hamiltonii. Five novel antioxidant compounds were isolated and characterized by NMR and MS. The compounds exhibited free radical scavenging activity in vitro and inhibited low-density lipoprotein oxidation. This study demonstrates that the root extract of D. hamiltonii is a cocktail of several antioxidant compounds with health implications.

Antioxidants↗

PubMed2006

Causal relationship between hexachlorocyclohexane cytotoxicity, oxidative stress and Na+, K +-ATPase in Ehrlich Ascites tumor cells.

Role of oxidative stress and Na+,K+-ATPase in the cytotoxicity of hexachlorocyclohexane (HCH) on Ehrlich Ascites tumor (EAT) cells has been studied. HCH caused dose dependent cell death as measured by trypan blue exclusion and lactate dehydrogenase (LDH) leakage from the cells. HCH induced oxidative stress in EAT cells which was characterized by glutathione depletion, lipid peroxidation (LPO), reactive oxygen species (ROS) production and inhibition of antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT). Protective effect of antioxidants on HCH induced oxidative stress was assessed, among the antioxidants used only quercetin inhibited HCH-induced LPO and ROS production as well as cell death whereas alpha -tocopherol, ascorbic acid and BHA inhibited LPO but not cell death. Inhibition of membrane bound Na+,K+-ATPase was a characteristic feature of HCH cytotoxicity in EAT cells. Experimental evidence indicates that HCH-induced cell death involves oxidative stress due to ROS production and membrane perturbation in EAT cells.

Animals↗

PubMed2005

Hexachlorocyclohexane differentially alters the antioxidant status of the brain regions in rat.

Hexachlorocyclohexane (HCH), a highly persistent organochlorine insecticide, is neurotoxic at acute doses and causes degenerative effects on chronic exposure. HCH has been reported to induce oxidative stress in cells and tissues. Mammalian brain is sensitive to oxidative stress which is implicated in neurodegenerative diseases. Effect of HCH on the brain regions, cortex, cerebellum, midbrain and brainstem, has been investigated by studying the response of antioxidant enzymes in rats treated orally with HCH at 25 and 100mg/kg b.w. for 2 weeks. Lipid peroxidation and glutathione depletion was seen in all the brain regions of HCH treated rats. The brain regions showed distinct variation in the antioxidant enzyme activities. Activities of glutathione peroxidase, glutathione reductase, glutathione-S-transferase and catalase were markedly induced whereas superoxide dismutase was inhibited at higher dose in all the brain regions. Marked induction and inhibition of the antioxidant enzymes, especially in the cortex and to varying degrees in other brain regions, was seen in HCH treated rats. These biochemical changes suggest vulnerability to oxidative stress in the brain is region-specific. Whether these changes are adaptive or compromise the capacity of the brain to deal with the HCH-induced oxidative stress that could lead to degenerative neurotoxic manifestations remain to be understood.

Administration, Oral↗

PubMed2005

Isolation of antioxidant compounds from the methanolic extract of the roots of Decalepis hamiltonii (Wight and Arn.).

The tuberous roots of Decalepis hamiltonii are consumed as pickles and beverages and are believed to possess health-promoting properties. We have investigated the antioxidant potential of the roots. The methanolic extract of the root showed a high antioxidant activity. The methanolic extract was fractionated on a silica gel column, which showed three major fractions with good antioxidant activity. The active fractions were further subjected to preparative thin layer and silica gel column chromatography, which yielded six pure compounds. The purified compounds were characterized by MS, 1H NMR, 13C NMR, and two-dimensional NMR spectroscopic techniques and identified as 2-hydroxy-4-methoxybenzaldehyde, p-anisaldehyde, vanillin, borneol, salicylaldehyde, and bis-2,3,4,6-galloyl-alpha/beta-D-glucopyranoside. The latter compound, named decalepin, is a new antioxidant molecule from the plant kingdom. The purified compounds showed antioxidant activities in in vitro assays such as inhibition of lipid peroxidation, hydroxyl radical, superoxide anion, and 1,1-diphenyl-2picrylhydrazyl radical scavenging. This is the first report of the antioxidant constituents of the roots of Decalepis hamiltonii.

Antioxidants↗

PubMed1999

In vitro sequestration of two organophosphorus homologs by the rat liver.

Bromophos (Bp) and ethylbromophos (EBp) are two structurally homologous organophosphorus insecticides (OP) which show a 24-fold difference in their toxicity to the laboratory rat (LD50--2215 and 91 mg/kg b.w., respectively). The role of rat liver in the sequestration of the OP oxons was studied based on carboxylesterase (CaE) inhibition in vitro. Bromoxon (Bo) and ethylbromoxon (EBo) were greater inhibitors of rat hepatic CaE than brain acetylcholinesterase (AChE) with IC50 values at nanomolar and picomolar levels, respectively. The capacity of the liver to sequester OPs was determined by measuring AChE inhibition pre-incubated with or without liver homogenate. AChE inhibition by Bo decreased with increasing concentration of liver tissue, whereas it was unaffected in the case of EBo. The results imply that liver tissue contains binding sites, which sequester Bo thereby reducing the number of OP molecules available to inhibit AChE. Although CaE inhibition leads to sequestration, other binding sites in the liver may have a significant role in determining the toxicity of OPs. Differential sequestration of the OPs by hepatic tissue, therefore, could be important in understanding the role of differential saturation of the target molecules, which has a bearing on differential toxicity.

Acetylcholinesterase↗

PubMed1997

A colorimetric assay method for 3beta-hydroxy-delta5-steroid dehydrogenase.

3beta-Hydroxy-Delta5-steroid dehydrogenase is an important enzyme of steroid hormone biosynthesis present in steroidogenic tissues like adrenal, testis, and ovary of vertebrates. The enzyme is assayed mainly by radiochemical substrates. Spectrophotometric assay is not adequately sensitive to detect the enzyme activity since it is often present in low levels. We have developed a simple colorimetric assay based on formazan formation due to the reduction of the tetrazolium salt. The reaction mixture containing the substrate, pregnenolone or dehydroepiandrosterone, NAD and iodonitrotetrazolium in 0.1 M Tris-HCl buffer (pH 7.8), and the enzyme extract is incubated for 1 h at 37 degrees C. Absorbance at 490 nm is read in a spectrophotometer. The enzyme activity was linear with time and protein concentration. The assay works well with adrenal tissue extract, whereas in the case of testis, Leydig cell preparation may be required. We have assayed the enzyme activity in the adrenal of rat, mouse, and gerbil. The method is two- to threefold more sensitive than the spectrophotometric assay.

Adrenal Glands↗

PubMed1996

Neurotoxicity and pattern of acetylcholinesterase inhibition in the brain regions of rat by bromophos and ethylbromophos.

Bromophos (Bp) and ethylbromophos (EBp) are two structurally homologous organophosphorus (OP) insecticides which show wide differences in their toxicity as well as neurotoxic symptoms in the laboratory rat. EBp is 24-fold more toxic (LD50 = 91 +/- 14 mg/kg body wt) than Bp (LD50 = 2218 +/- 195 mg/kg body wt) and only EBp produced characteristic tremors and lacrimation. In vivo cholinesterase inhibition was in the order plasma > erythrocytes > brain. Experiments with equitoxic and equimolar doses showed that EBp is a more potent anticholinesterase compound than Bp. Since IC50 values for the brain AChE were similar for both OPs, the target enzyme sensitivity was not a major factor in their differential toxicity. In vitro reactivation of serum ChE was significantly higher in the case of EBp than that of Bp. AChE in the brain regions showed differential inhibition in vivo. The brain stem AChE inhibition was least by Bp, whereas it was highest in the case of EBp. Both the OPs produced high AChE inhibition in the hippocampus. Differential inhibition of AChE in the brain regions and its consequent effects may be important factors in the differential neurotoxicity of OPs.

Animals↗

PubMed1992

Effect of vitamin A on hexachlorocyclohexane (HCH) toxicity in the rat.

1. Technical hexachlorocyclohexane (HCH) depleted hepatic stores of vitamin A in male albino rats to cause secondary vitamin A deficiency. 2. Toxicity of HCH in rats is augmented by dietary vitamin A-deficiency as evidenced by growth retardation, organ hypertrophies and alterations in the serum and liver levels of the marker enzymes of toxicity. 3. Supplementation of dietary vitamin A to the rats either in adequate (2000 IU/kg diet) or in an excess but not hypervitaminotic level (10(5) IU/kg diet) resulted in significant protection against the toxicity of HCH. 4. The activities of the hepatic xenobiotic metabolizing enzymes were generally low (with the exception of glutathione S-transferase) in the vitamin A-deficient rats compared to those of the vitamin A supplemented diet groups. 5. The results indicated that dietary vitamin A influences the response of male albino rats to HCH toxicity possibly by modulating the activities of hepatic xenobiotic metabolizing enzymes.

Animals↗

PubMed1991

Conserved N-terminal sequences in homologous subunits of the multicatalytic proteinase complex (proteasome).

The bovine lens multicatalytic proteinase complex (MPC) (MW 700 kDa) comprises at least twelve subunits in the molecular mass range 22-35 kDa. Three of the subunits, L1 (27 kDa), L2 (24 kDa) and L3 (29 kDa), were purified by reverse phase HPLC. Their amino acid composition and N-terminal sequences indicate that they are not identical. L1 and L2 subunits show very high (greater than 90%) sequence homology with specific subunits of rat liver and human reticulocyte MPC and these are considered to be homologous components of the MPC which are highly conserved in evolution.

Amino Acid Sequence↗

PubMed1990

Protective role of vitamin A in the male reproductive toxicity of hexachlorocyclohexane (HCH) in the rat.

The reproductive toxicity of the organochlorine insecticide, hexachlorocyclohexane (HCH), was investigated in male albino rats fed a diet free of vitamin A or containing vitamin A at 2000 or 100,000 IU/kg diet. Diets containing 1000 ppm HCH for 7 weeks did not cause testicular toxicity in the vitamin-A-deficient and supplemented rats. However, reproductive toxicity was clearly manifested 2 weeks after withdrawing HCH from the diets and was more pronounced in the vitamin A deficient rats compared to their vitamin A supplemented counterparts. Reduction in the testicular weights was accompanied by atrophy of epididymides and seminal vesicles in the vitamin A deficient rats alone. Inhibition of spermatogenesis was further confirmed by decreased sperm count in the epididymis. Biochemically, the activities of the steroidogenic enzymes were drastically reduced. Supplementation of vitamin A after withdrawal of HCH accelerated the recovery and restored spermatogenesis and enzyme activities in the deficient rats. These results demonstrate the greater susceptibility of the male reproductive system to HCH toxicity during vitamin A deficiency and also the protective effect of vitamin A supplementation.

Animals↗

PubMed1988

Response of blood and brain cholinesterase to dermal exposure of bromophos in the rat.

Response of cholinesterase to dermal exposure of acute, single and multiple doses of Bromophos in the female rat has been studied. Dose-response studies (50-4000 mg/kg body weight, 24 h exposure) showed that plasma cholinesterase was most sensitive to inhibition in vivo, followed by the brain and erythrocyte acetylcholinesterase. The ID50 values for the in vivo cholinesterase inhibition were 10.1, 576.1 and 1938.0 mg/kg body weight for the plasma, brain and erythrocytes, respectively. In time-course studies after a single sublethal dose of 1000 mg/kg body weight (24 h) of Bromophos, the serum and brain cholinesterase were rapidly inhibited reaching a maximum at 16 h. Recovery was complete in the case of serum at 14 days post-exposure, whereas the brain enzyme was not fully recovered at 21 days. In a subacute study, daily dermal application of 50 mg/kg body weight of Bromophos for 5 and 10 days, resulted in high inhibition of the serum cholinesterase and brain acetylcholinesterase, the former being more marked which was reversible after 10 or 15 days of post-exposure period. Very low levels of dermal exposure of Bromophos (10-50 mg/kg body weight) for 17 days caused pronounced depression of serum cholinesterase which completely recovered in 15 days after cessation of exposure suggesting that the serum cholinesterase could serve as the most sensitive diagnostic indicator of Bromophos exposure.

Animals↗

PubMed1983

Hexachlorocyclohexane-induced testicular dysfunction in rats.

Weanling male albino rats were fed 100, 750 and 1500 p.p.m. of technical HCH for 90 days. There was marked testicular atrophy with reduced tubule size and spermatogenetic arrest at 1500 p.p.m. Histochemically, there was accumulation of cholesterol-positive lipids in the Sertoli cells and the Leydig cells of the atrophied testis and biochemical estimation revealed significant increase of total lipid and cholesterol contents. Activities of delta 5 3 beta hydroxysteroid dehydrogenase (delta 5 3 beta HSDH), 17 beta hydroxysteroid dehydrogenase (17 beta HSDH) and glucose-6-phosphate dehydrogenase (G-6-PDH) in the interstitial cells were markedly decreased suggesting steroidogenic inhibition in the Leydig cells of the atrophied testis due to HCH feeding.

Animals↗

PubMed1983

Testicular atrophy in Gallus domesticus fed acute doses of copper fungicides.

Acute oral toxicity of the copper fungicides, copper sulphate and copper oxychloride, were studied in male Gallus domesticus. The median lethal dose for copper sulphate and copper oxychloride determined were 693 and 1263 mg/kg body weight, respectively. Severe diarrhea and delayed mortality (3 to 6 days) was characteristic of copper oxychloride. Liver weights were nearly doubled in birds fed copper oxychloride and marked dose-dependent testicular atrophy was noticed in both copper sulphate and copper oxychloride fed birds. Mild to severe spermatogenetic arrest concomitant with testicular atrophy was observed. Histochemically, the interstitial (Leydig) cells and seminiferous tubules showed intense accumulation of cholesterol-positive lipids. The degree of lipophilia appeared to be directly proportional to the extent of spermatogenetic arrest, and these results are suggestive of steroidogenic inhibition in the Leydig cells of the atrophied testis.

Animals↗

PubMed1982