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Biomedical subjects

S D Varma

Publications and source records attributed to S D Varma.

At least 73 records · Page 4Linked to original sources
PubMed1987

Hexose monophosphate shunt in rat lens: stimulation by vitamin C.

The metabolism of glucose through the hexose monophosphate (HMP) shunt has been studied in rat lens in vitro, in the absence and presence of ascorbic and dehydroascorbic acids. Both forms of the vitamin stimulated the utilization of glucose through the HMP shunt, the stimulatory effect of dehydroascorbate being substantially greater than that of ascorbate. The stimulatory effect of ascorbate, as well as of dehydroascorbate, was antagonized by sodium iodide, and N,N-bis (dichloroethyl)-N-nitrosourea, compounds known to inhibit glutathione reductase. N-ethylmaleimide also antagonized the stimulation. These findings, therefore, suggest that the DHA/AA redox couple acts in concert with the GSSG/GSH couple in stimulating the tissue shunt activity.

Animals↗
PubMed1986

In vitro damage to rat lens by xanthine-xanthine oxidase: protection by ascorbate.

The potential of ascorbic acid acting against the toxic effects of active oxygen species on the lens has been studied. The active species of oxygen were generated by the action of xanthine oxidase on xanthine. Rat lenses incubated in medium containing xanthine and xanthine oxidase were physiologically damaged, as evidenced by the decrease in the ability of the tissue to accumulate rubidium or alpha-aminoisobutyric acid against a concentration gradient. The pressure of ascorbate in the medium protected against the tissue damage. One of the functions of high ascorbate in the aqueous humor of many primates including human beings may, therefore, be to protect the lens and other surrounding tissues against the toxic effects of active oxygen derivatives produced in situ under ambient, as well as under photochemical, conditions.

Aminoisobutyric Acids↗
PubMed1986

Photodamage to the lens in vitro: implications of the Haber-Weiss reaction.

Studies have been conducted to examine the implications of photochemical generation of O2- and its derivatization to H2O2 and OH . in the physiology of the lens in vitro. Physiological status was determined by measuring the uptake of rubidium by the intact tissue when cultured in riboflavin-containing medium, in dark and light, and in the presence and absence of various scavengers. In the presence of light, the uptake of rubidium in the lens was greatly diminished; this suggests photodamage to the tissue. MnSOD and ferricyanide protected against this photochemical damage. The damaging process was thus initiated by the generation of O2-. The tissue damage was also attenuated by catalase, ferrocyanide, and mannitol. These results, therefore, suggest the participation of hydrogen peroxide and the subsequent Haber-Weiss reaction in the photodamaging process.

Animals↗
PubMed1986

Vitamin C in the human aqueous humor and cataracts.

Blood, aqueous humor and cataracts obtained from an Indian population were analyzed for ascorbic acid content. While the concentrations of ascorbic acid in the blood and cataracts were similar in patients with cortical and nuclear cataracts, the level of this nutrient was lower in the aqueous humor of patients with cortical cataracts. This suggests a sluggish transport of ascorbate from the blood to the aqueous humor in the latter group. It is possible that this lower level of ascorbate might be one of the factors participating in cataractogenesis. The lower aqueous ascorbate in the group with the cortical cataracts could not be accounted for by any dietary deficiency of this nutrient. Hence, it appears metabolically related.

Age Factors↗
PubMed1984

Polyol pathway metabolites in human cataracts. Correlation of circulating glycosylated hemoglobin content and fasting blood glucose levels.

Circulating glycosylated hemoglobin (Hb A1) and/or fasting blood glucose (FBG) levels, measures of the extent to which diabetes is clinically controlled, were correlated with the contents of fructose, sorbitol, glucose, and inositol in 27 cataracts removed by intracapsular extraction. In the series of patients studied, Hb A1 levels ranged from 6.0% to 15.5% of the total hemoglobin value. The levels of fructose and sorbitol (micromoles per gram of lens) in their cataracts ranged from 0 to 8.4 and 0 to 10.2 mumole/g, respectively, with correlation coefficients greater than .8. Similar correlations were noted with FBG. The Hb A1 correlated with lens glucose (r = .58) and not with inositol. However, FBG had no correlation with either lens glucose or inositol. The observed correlation of the polyol pathway metabolites with both Hb A1 and FBG suggests that the lens can synthesize substantial quantities of sorbitol and fructose in response to the excess glucose available to lenses of human diabetics. A synergistic role of the polyol pathway in the cause of senile cataracts is thus possible.

Blood Glucose↗
PubMed1984

Oxidative stress on lens and cataract formation: role of light and oxygen.

The mechanism of oxidative damage to the lens through intraocular photochemical generation of superoxide and its derivatization to other oxidants such as singlet oxygen, hydroxyl radical and hydrogen peroxide has been studied. Rat lenses when organ cultured aerobically in TC 199 containing additional amounts of riboflavin were damaged as demonstrated by an inhibition of the uptake of Rb 86 against a concentration gradient. The pump was not affected by light if the culture was conducted in the basal TC 199. However, light was observed to induce significant peroxidative degradation of the tissue lipids even in the basal medium, the degradation being indicated by the formation of malonaldehyde. Both the inhibition of the pump as well as the peroxidative degradation of the tissue lipids, were attenuated considerably by scavengers of superoxide and hydrogen peroxide. In addition, the lipid degradation was prevented by vitamins C and E. The results suggest that the photodynamic injury to the lens cation pump as well as to membrane lipids is incumbent upon an initial generation of superoxide and its derivatization to other oxidants. Thus, the ocular lens is susceptible to oxidative insult and physiological damage through photocatalytic generation of various oxygen radicals. Large concentrations of ascorbic acid in the aqueous humor seems to be able to provide significant protection against such an insult. Thus, this may be one of the functions of high concentration of ascorbic acid in the aqueous humor. The implication of oxidative stress has also been examined in the genesis of cataracts in vivo. Treatment with vitamin E of the Emory mouse led to a decrease in the rate of cataract progression suggesting that at least in some instances an oxidative stress could participate in the formation of cataracts. Oxygen radicals may inflict damage at multifarious biochemical sites. Human lens lipids were also shown to have an absorption maxima at 239 nm indicating their susceptibility to oxidative degradation. In addition the lipid extract has fluorescence similar to that of lipofuscins. The levels of MDA were higher in the brunescent cataracts as compared to that in the nonbrunescent cataracts. The implications of oxidative stress towards the genesis of cataracts in humans is being explored further.

Animals↗
PubMed1983

Galactitol accumulation by glucose-6-phosphate deficient fibroblasts: a cellular model for resistance to the complications of diabetes mellitus.

When incubated in high galactose media, fibroblasts from individuals with the severe (Mediterranean) variety of glucose-6-phosphate dehydrogenase (G6PD) deficiency accumulate significantly less galactitol than do fibroblasts from matched control subjects. The effect is not observed in fibroblasts from black subjects with the more common, and milder, A- variant of G6PD deficiency. Since aldose reductase and sorbitol dehydrogenase activities in experimental and control fibroblasts are identical, the effect is most likely due to the substantial reduction in NADPH levels in severely G6PD-deficient cells. Sorbitol does not accumulate either in control or in G6PD deficient fibroblasts incubated in high glucose medium, most likely because of the action of sorbitol dehydrogenase, and the presence of a carrier-mediated glucose transport system in the cell membrane which limits the concentration of glucose that can accumulate in these cells.

Adolescent↗
PubMed1983

Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin.

The inhibition of human lens aldose reductase by flavonoids has been studied. Quercetin, the major pentahydroxyflavone, was observed to inhibit human lens aldose reductase by 50% at a concentration of 5 X 10(-6) M. The inhibitory activity of its 3-O-glucoside was similar to that of the parent aglycon. Glycosidation with L-sugar (quercitrin and guaijaverin), however, improved the inhibitory activity (the IC50 values being 1 X 10(-6) M and 2.5 X 10(-6) M respectively). The improvement in inhibitory activity with glycosidation with L-sugar was also apparent from the high inhibitory activity of myricitrin as compared to myricetin, although the improvement in this case of hexahydroxy flavone glycosidation was significantly less than in the case of penthahydroxy flavone glycosidation. The structure-activity relationship observed for human lens enzyme was similar to that reported previously for rat lens enzyme. Inhibitory activity on the whole however, was lower with human lens enzyme. Some known inhibitors of cyclo-oxygenase such as indomethacin, aspirin and sulindac also inhibited human lens aldose reductase. Thus, an inhibitor of one of the enzymes may actually inhibit both and, when administered, may exert mixed physiological effects.

Aldehyde Reductase↗
PubMed1983

Sugar cataracts in Mongolian gerbil (Meriones unguiculatus).

Mongolian gerbils (Meriones unguiculatus) given a 50% galactose diet developed cataracts similar to those produced in rats maintained on the same diet. This report describes the various stages through which the cataracts progressed. The first sign of a cataract appeared 24 hr after feeding gerbils on the high galactose diet. The pace of cataract maturation was observed to be about twice of that in rats, although the blood galactose levels were similar in the two species. Aldose reductase activity in the gerbil lens was also about twice of that in the rat lens. In conformity with this, dulcitol accumulated to a higher level in gerbil lens during the early phase of cataractogenesis. The data are, therefore, in accordance with the concept that excessive accumulation of polyol in the lens initiates cataract development. The gerbil thus appears to be another suitable model for the study of sugar cataracts.

Aldehyde Reductase↗
PubMed1983

X-ray effects on lens DNA-implications of superoxide (O(2)).

The photochemical generation of superoxide (O(2)) during in vitro exposure of bovine lenses induced damage in the structure of lens DNA as indicated by hyperchromicity and Tm measurements. The damage in lens DNA was significantly protected by the inclusion of superoxide dismutase (SOD), glutathione (GSH) and ascorbate in the incubation medium before X-ray exposure. The protection by SOD, GSH and ascorbate occurred due to their interaction with O(2) radicals. These results thus indicate the deleterious effect of O(2) in lens physiology and the protective role of such compounds against radiation damage.

Animals↗
PubMed1983

Aldose reductase activity in retinal and cerebral microvessels and cultured vascular cells.

Isolated microvessels (primarily capillaries) from bovine retina and cerebral cortex, as well as cultured bovine retinal capillary pericytes and porcine and canine retinal capillary endothelial cells contain apparent aldose reductase activity. This conclusion is based on the ability of these cultured cells and vessel fragments to reduce DL-glyceraldehyde in preference to D-glucuronate at low (0.1 mM) substrate concentrations, in the presence of NADPH, and in the accumulation of high levels of sorbitol or galactitol when retinal pericytes and endothelial cells are cultured in media enriched in glucose or galactose. The quantitative similarities of these activities in bovine retinal and cerebral microvessels, as well as the quantitatively similar ability of these two sets of microvessels to oxidize 14C-labeled glucose with the label either in the C-1 or the C-6 position, suggests that aldose reductase may not be a major causal factor in diabetic retinopathy. This conclusion is suggested because, while these metabolic activities are similar in bovine retinal and cerebral microvessels, only the retinal microvasculature suffers major anatomic and functional damage in diabetes. This conclusion must be viewed with caution, however, because other metabolic pathways that we have not investigated may be altered by an excess of sugar alcohols, and be present in differing activities in retinal and cerebral microvessels; species differences may exist; and similar experiments have not been conducted using human microvessels.

Aldehyde Reductase↗
PubMed1982

Photoperoxidation in lens and cataract formation: preventive role of superoxide dismutase, catalase and vitamin C.

Exposure of rat lens to fluorescent daylight (150 ft candles) under tissue culture conditions led to a substantial lipid peroxidation as evidenced by the formation of malonaldehyde (MDA). MDA content of lenses incubated overnight in presence of such light was approximately sixfold of that in the control lenses cultured in the dark. These cultures were maintained in physiological medium resembling aqueous humor which does not contain any additional photoactive component. Thus, the lens in its physiological surroundings is susceptible to photoperoxidation by light of wavelengths which freely penetrate the eye. Photoperoxidation could be thwarted by superoxide dismutase, catalase, and ascorbate, suggesting that the observed peroxidative degradation is initiated by photocatalytic generation of superoxide and its subsequent derivation to other potent oxidants. These studies provide for the first time suggestive evidence that senile cataract development may in part be linked to the in vivo photochemical generation of superoxide and other potent oxidants in the aqueous humor and lens derived from the ambient oxygen and light; and ascorbate which is maintained at high levels in this fluid by virtue of its active transport from plasma, is physiologically important in preventing the deleterious action of these potent oxidants. The studies thus indicate for the first time the possibilities of a hitherto unrecognized role of ascorbate against cataracts and other age-, light- and oxygen-dependent ocular abnormalities, In addition, the study re-emphasizes the role of tissue catalase and superoxide dismutase in the prevention of photoperoxidative damages to the tissue.

Animals↗