Biomedical subjects

S D Varma

Publications and source records attributed to S D Varma.

At least 37 records · Page 2Linked to original sources

PubMed1998

Corneal damage by half mustard (2-chloroethyl ethyl sulfide, CEES) in vitro preventive studies: a histologic and electron microscopic evaluation.

The effect of half-mustard (2-chloroethyl ethyl sulfide, CEES) on the morphology and ultrastructure of the cornea has been studied in vitro. Extensive necrotic changes were observed histologically as well as electron microscopically. The outer layer of corneal epithelium was observed to undergo vacuolization and globulization prior to its denudation. The epithelium becomes separated from the Bowman's membrane. These necrotic changes are prevented from taking place in the presence of a mixture of taurine, pyruvic acid, alpha-keto glutaric acid and pantothenic acid suggesting the use of this mixture in the prevention of mustard damage.

Animals↗

PubMed1998

Half mustard (CEES) induced damage to rabbit cornea: attenuating effect of taurine-pyruvate-alpha-ketoglutarate-pantothenate mixture.

Studies have been conducted on the corneal damage by half mustard (2-chloroethyl-ethyl sulfide, CEES) and its possible prevention by a mixture of taurine, alpha-ketoglutarate, pyruvate and pantothenate. CEES has been found to damage the membrane permeability function of the corneal epithelium as evidenced by increased flux of the rubidium ion from the epithelial to the endothelial side. The cornea also loses its transparency. These damaging effects are preventable by the above mixture labeled as VM. It is conceived that use of such a mixed formulation may provide a pharmacological means of prophylactic and post-exposure treatment against the tissue damage caused by exposure to the mustards.

Animals↗

PubMed1998

Prevention of intracellular oxidative stress to lens by pyruvate and its ester.

Pyruvate is a well-known scavenger of hydrogen peroxide (H2O2). In addition, it scavenges superoxide radical (O2.-). However, evidence on its intracellular antioxidant function is meager at present. Hence, we have examined the effectiveness of this metabolite and its ethyl ester against intracellular oxidative damage to the lens under organ culture. Menadione, a redoxcycling quinone, was used to generate the reactive oxygen species (ROS). It was found to inhibit lens metabolism as evidenced by a decrease of ATP. Additionally, tissue oxidation was apparent by loss of glutathione (GSH), and increase in the level of oxidized glutathione (GSSG), coupled with increase of the urea soluble proteins (water insoluble). The overall physiological damage was apparent by the inhibition of the Na+-K+-ATPase dependent cation pump, as evidenced by a decreased rubidium transport. These deleterious effects were attenuated by pyruvate and ethyl-pyruvate. The later was found to be more effective.

Adenosine Triphosphate↗

PubMed1998

Delayed manifestation of ultra violet radiation induced erythema in guinea pigs by sodium pyruvate--a free radical scavenger.

Sodium pyruvate, a free radical scavenger was evaluated for anti-inflammatory activity using UV radiation induced dermal erythema on guinea pig and compared with that of standard naproxen. Oral as well as topical pyruvate exhibited significant activity against UV induced dermal erythema model and the activity was comparable to that of naproxen. In the other pharmacodynamic studies, such as the studies on rat blood pressure, isolated guinea pig ileum and rat uterus, it showed no effect on any of these. In conclusion, sodium pyruvate showed a significant protection in the UV induced dermal erythema in guinea pigs. It also showed good absorption in UV-B range and this property can be utilised to develop the sodium pyruvate as a sunscreening agent.

Animals↗

PubMed1997

Formation of advanced glycation end (AGE) products in diabetes: prevention by pyruvate and alpha-keto glutarate.

Glycation of proteins and their subsequent structural and functional modifications have been ascribed to play a prominent role in the pathogenesis of several secondary complications of diabetes, such as cataract and retinopathy. In addition, it plays a role in the generalized ageing process as well. Investigations have been conducted to explore the possibility of preventing the above process by use of pyruvate and alpha-keto glutarate as representatives of physiologically compatible keto acids. The results demonstrate that both these compounds are effective in preventing the initial glycation reaction as well as the formation of AGE products. Both these compounds also inhibit the generation of high molecular weight aggregates associated with cataract formation. Mechanistically, the preventive effects appear to be due to (1) competitive inhibition of glycation by the keto acids and (2) the antioxidant (radical scavenging) properties of these compounds. The results are hence considered useful from the point of view of developing these and other keto acid derivatives as pharmacological agents useful in preventing glycation related protein changes and consequent tissue pathological manifestations.

Animals↗

PubMed1997

Prevention of lens protein glycation by taurine.

Modifications in lens protein structure and function due to nonenzymic glycosylation and oxidation have been suggested to play a significant role in the pathogenesis of sugar and senile cataracts. The glycation reaction involves an initial Schiff base formation between the protein NH2 groups and the carbonyl group of a reducing sugar. The Schiff base then undergoes several structural modifications, via some oxidative reactions involving oxygen free radicals. Hence certain endogenous tissue components that may inhibit the formation of protein-sugar adduct formation may have a sparing effect against the cataractogenic effects of sugars and reactive oxygen. The eye lens is endowed with significant concentration of taurine, a sulfonated amino acid, and its precursor hypotaurine. It is hypothesized that taurine and hypotaurine may have this purported function of protecting the lens proteins against glycation and subsequent denaturation, in addition to their other functions. The results presented herein suggest that these compounds are indeed capable of protecting glycation competitively by forming Schiff bases with sugar carbonyls, and thereby preventing the glycation of lens proteins per se. In addition, they appear to prevent oxidative damage by scavenging hydroxyl radicals. This was apparent by their preventive effect against the formation of the thiobarbituric acid reactive material generated from deoxy-ribose, when the later was exposed to hydroxyl radicals generated by the action of xanthine oxidase on hypoxanthine in presence of iron.

Animals↗

PubMed1997

Nitrite-induced photo-oxidation of thiol and its implications in smog toxicity to the eye: prevention by ascorbate.

Studies have been conducted on nitrite-induced oxidation of corneal thiols and reduced glutathione (GSH). Oxidation of GSH in the presence of nitrite (NaNO2) was minimal in the dark. Exposure of GSH to UV (365 nm) in the presence of nitrite substantially accelerated this oxidation; only < 10% of the original GSH remained at the end of 20 minutes. A similar Thiol depletion was observed in the case of corneal epithelial extracts irradiated with UV in the presence of the nitrite. Nitrite is therefore considered to be a potent phototoxicant with possible pathophysiological implications to the external eye tissues. Ascorbate was found to be effective in preventing thiol oxidation, suggesting the possibility of preventing nitrogen oxide-based smog irritation to the eye by this physiologically compatible antioxidant.

Animals↗

PubMed1996

Studies on L-threose as substrate for aldose reductase: a possible role in preventing protein glycation.

L-threose is a product of ascorbate oxidation and degradation. By virtue of its free aldehyde group it can form Schiff-bases with tissue proteins, altering their normal function. In this study, we have examined the possibility of its detoxification to L-threitol by aldose reductase in the lens. The rat lens enzyme present in fresh homogenate as well as after 100 fold purification was found to utilize L-threose with a km of 7.1 x 10(-4) M. The specificity of the reaction was affirmed by its inhibition with sorbinil and quercetin, the well known aldose reductase inhibitors. Further studies on the role of this enzyme in preventing toxicity due to degradation products of ascorbate are in progress.

Aldehyde Reductase↗

PubMed1996

Oxyradical scavenging effects of dehydroascorbate.

Dehydroascorbate (DHA) has been shown to possess vitamin C like activities as well as to protect the lens against oxidative stress and cataract formation. The results presented here suggest that some of the beneficial effects of DHA can be attributed to its property of undergoing peroxidative decarboxylation and of O2-. scavenging. Incubation of 1-14C-DHA with peroxide at physiological pH has been found to liberate 14CO2 in quantitative yields, with recovery of 79-94%. The recovery increases with the increase in the amount of DHA used. Its O2-. scavenging activity was apparent by inhibition of O2-. dependent reduction of ferricytochrome c and nitroblue tetrazolium. The authenticity of the latter mechanism was proved by inhibition of the O2-. dependent reactions also by superoxide dismutase.

Decarboxylation↗

PubMed1995

Levels of superoxide dismutase mRNA in rat lens: effect of aging.

Superoxide dismutase, the enzyme catalyzing the dismutation of O2.- to H2O2 is known to be present in various ocular and nonocular tissues. In this communication we have determined the gene expression of this enzyme in rat lenses. The investigations have been conducted as a function of age using RNase protection assay. These in vitro assays for the corresponding mRNA suggested that the transcription of the gene is age variant, increasing as a function of age. The levels were significantly lower in the young lenses in comparison to the older lenses.

Aging↗

PubMed1995

Prevention of cataracts by nutritional and metabolic antioxidants.

Among aging disabilities, the one associated with the progressive decline of vision is functionally most disadvantageous. Cataracts are one of the more common causes of such visual disability. Several predisposing factors have been identified in the genesis of this disease. While it is perhaps a multifactorial process, significant developments have taken place in recent years suggesting that oxygen radicals are involved in the development of this aging manifestation. Antioxidant enzymes, such as catalase and superoxide dismutase, have been demonstrated to protect the lens cell membrane from oxidative stress as reflected by the prevention of the Na(+)-K(+)-ATPase-dependent pump deterioration due to oxyradical-dependent oxidation of its proteins and lipids. From the nutritional point of view, antioxidants such as ascorbate and vitamin E also offer significant protection to the lens against damage due to oxidative stress. Evidence regarding the protective effect of these nutrients has been based on lens organ culture studies in the presence of active oxygen, generated photochemically as well as enzymatically. The experiment involving photochemical environs simulate the status of the eye during the photopic vision. In vivo, the effectiveness of ascorbate against cataracts has been tested in rat pups developing cataracts under the oxidative influence of sodium selenite. Certain antioxidants produced metabolically also may be useful in protecting against cataracts. Pyruvate produced in glucose metabolism seems to be an important antioxidant. The efficacy of this compound has been tested within in vitro organ culture as well as in vivo, the latter experiments being done with selenite-treated rats. There is a hope that these and other nutritional and metabolic antioxidants may one day be useful in delaying or even preventing cataract formation in human beings.

Animals↗

PubMed1995

Inhibition of polyol formation in rat lens by verapamil.

Accumulation of sorbitol and xylitol in rat lenses incubated in medium-199 with and without verapamil has been studied. This antihypertensive drug, known to attenuate hypertension by its calcium channel blocking effect, is also known to inhibit cataract formation in diabetes. The present studies have demonstrated that verapamil's effect against cataract could also be partially related to its aldose reductase inhibitory activity, in addition to the Ca++ channel blocking activity. The accumulation of sorbitol in the lenses incubated with high glucose in the presence of 400 microM verapamil was only 2.3 mmoles/Kg wet weight against 11.3 mmoles/Kg in its absence. The level of xylitol attained in the presence of 10 mM xylose was 25.7 +/- 2.4 mmoles/Kg. It decreased to 4.8 +/- 1.2 mmoles/Kg in presence of 400 microM verapamil. Hence, verapamil is significantly effective in inhibiting lens aldose reductase dependent polyol synthesis, an action simultaneous with its effect on calcium penetration.

Aldehyde Reductase↗

PubMed1995

Peroxide damage to rat lens in vitro: protective effect of dehydroascorbate.

The possible protective effect of dehydroascorbate against peroxide damage to rat lens under in vitro organ culture has been studied by measuring the levels of ATP, GSH and the uptakes of rubidium and alpha-aminoisobutyric acid. All these parameters were adversely affected by the presence of 0.5 mM hydrogen peroxide in the culture medium. Dehydroascorbate (1 mM) protected the lens against such effects. The protective effect is tentatively attributable to the utilization of peroxide in peroxidative decarboxylation of the dehydroascorbate, in a manner similar to that of other alpha-ketoacids.

Adenosine Triphosphate↗

PubMed1995

Oxidative denaturation of lens protein: prevention by pyruvate.

The denaturation of lens proteins as apparent by the generation of protein carbonyl in the presence of active oxygen and the prevention of such denaturation by pyruvate were studied. Active oxygen was generated by the action of xanthine oxidase on xanthine under aerobic conditions. Rat lens protein when incubated with xanthine and xanthine oxidase produced significant amounts of the carbonyl derivative. The formation of such carbonyl was substantially inhibited by pyruvate. In addition, the keto acid also was found to stimulate the utilization of glucose through HMP shunt, a mechanism known to transport reducing equivalents from glucose to peroxide. The results suggest that pyruvate exerts a beneficial effect in attenuating the age-related protein modifications and consequent physiological impairments. These studies are also considered useful from the therapeutic point of view.

Animals↗

PubMed1995

H2O2 determination in rat lens: chemiluminescent versus radioisotopic methods.

Hydrogen peroxide levels have been determined in rat lenses by using two methods, a chemiluminescent and a radioisotopic method. The average content was found to be 155 +/- 20 and 127 +/- 18 nmol/g wet weight of the tissue, respectively, by the two methods. The reaction of H2O2 with dichlorophenol-indophenol in the presence of peroxidase was also studied. However, this was found to be less suitable. The results of the chemiluminescent determinations are similar to the results with the radioisotopic methods demonstrating the feasibility of determining H2O2 by chemiluminescence measurement as well.

2,6-Dichloroindophenol↗

PubMed1995

Prevention of oxidative damage to rat lens by pyruvate in vitro: possible attenuation in vivo.

Studies have been conducted to assess the possible preventive effect of pyruvate against lens protein oxidation and consequent denaturation and insolubilization. Rat lens organ culture system was used for these studies. The content of water insoluble proteins (urea soluble) increased if the lenses were cultured in medium containing hydrogen peroxide. Incorporation of pyruvate in the medium prevented such insolubilization. The insolubilization was associated primarily with loss of gamma crystallin fraction of the soluble proteins. PAGE analysis demonstrated that insolubilization is related to -S-S- bond formation which was preventable by pyruvate. Since pyruvate is a normal tissue metabolite the findings are considered pathophysiologically significant against cataract formation. This was apparent by the prevention of selenite cataract in vivo by intraperitoneal administration of pyruvate.

Adenosine Triphosphate↗

PubMed1995

Dehydroascorbate reductase activity in bovine lens.

The bovine lens was studied for the presence of dehydroascorbate reductase activity. The activity was found to be restricted primarily to the mitochondrial fraction isolated from the cortex-epithelial fraction of the tissue. It was not detectable in the cytosolic fraction. The Km of reaction with dehydroascorbate was approximately 0.45 mM. These studies suggest that the reduction of dehydroascorbate to ascorbate in the mitochondria takes place enzymatically as well as nonenzymatically, GSH being the source of reducing electrons in both the cases. The enzymatic mechanism may assume a greater role in situations of oxidative stress which lead to GSH depletion. The presence of this enzyme in the mitochondria is considered with a normally more severe oxidative condition therein.

Animals↗

PubMed1994

Studies on Emory mouse cataracts: oxidative factors.

Emory mouse cataracts were analyzed for amino acids, protein carbonyls and fatty acids. The tissue membrane integrity was assessed by studying chromium-51 efflux. An effect of vitamin E-free diet on cataract progression was also studied. Chromium leakage was faster from the cataractous lenses, indicating a generalized membrane damage. This was also apparent from the loss of amino acids. The damage involves oxidation of proteins, as well as of lipids. Protein oxidation was apparent by a hydrazone formation with 2,4-dinitrophenyl hydrazine. The lipid oxidation was apparent from a decrease in oleic acid and appearance of the corresponding ketoacids. Lipid oxidation was also apparent by an attenuating effect of vitamin E.

Amino Acids↗