The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Joseph R Dynlacht - One of the best experts on this subject based on the ideXlab platform.
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the role of age sex and steroid sex hormones in radiation Cataractogenesis
Radiation Research, 2013Co-Authors: Joseph R DynlachtAbstract:It is critical to identify and gain a better understanding of the factors that enhance or reduce the risk of Cataractogenesis, to minimize the possibility of occurrence after deliberate (e.g., radiation therapy, interplanetary travel) or unintentional exposure to ionizing radiation. Both gender and age at the time of exposure have been established as key determinants of Cataractogenesis induced by sparsely ionizing (low-LET) and densely ionizing (high-LET) radiation. However, animal data from several older studies are often conflicting and somewhat difficult to interpret, in that the experiments suffered from small group sizes, limited dose ranges or short periods of observation, and human data are sparse or statistical significance is sometimes limited. Steroid sex hormones (SSH) may underlie age and gender-based differences in the progression and prevalence of cataracts that otherwise occur spontaneously in humans and animal models, and may also underlie age and sex-related differences in radiation cata...
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age and hormonal status as determinants of Cataractogenesis induced by ionizing radiation i densely ionizing high let radiation
Radiation Research, 2012Co-Authors: Joseph R Dynlacht, Shailaja Valluri, Joy Garrett, Marc S Mendonca, Jennifer T Lopez, Andrea Caperellgrant, Robert M BigsbyAbstract:Age at the time of exposure to sparsely ionizing radiation has been established as a key determinant of radiation Cataractogenesis. However, while some reports suggest that the lenses of the young are hypersensitive, data from older studies are often conflicting and somewhat difficult to interpret when the radioresponse of young lenses is compared to that of adult lenses. Moreover, the mechanism of the age-response function for radiation Cataractogenesis has yet to be identified. Since steroid sex hormones, notably estradiol, appear to play a role in age-related Cataractogenesis, we hypothesized that the age response for radiation Cataractogenesis could be dictated by estradiol status. We recently showed that exposure to high-linear energy transfer (LET) radiation resulted in a reduced latent period for, and enhanced progression of cataracts in rats that were 1 year old at the time of exposure compared to those that were 56 days old. However, the enhanced sensitivity of older lenses compared to younger le...
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Age and hormonal status as determinants of Cataractogenesis induced by ionizing radiation. II. Sparsely ionizing (low-LET) radiation.
Radiation research, 2012Co-Authors: Joseph R Dynlacht, Shailaja Valluri, Joy Garrett, Colleen Desrosiers, Jessica Nees, Andrea Caperell-grant, Robert M BigsbyAbstract:Age at the time of exposure to sparsely ionizing radiation has been established as a key determinant of radiation Cataractogenesis. However, while some reports suggest that the lenses of the young are hypersensitive, data from older studies are often conflicting and somewhat difficult to interpret when the radioresponse of young lenses is compared to that of adult lenses. Moreover, the mechanism of the age-response function for radiation Cataractogenesis has yet to be identified. Since steroid sex hormones, notably estradiol, appear to play a role in age-related Cataractogenesis, we hypothesized that the age response for radiation Cataractogenesis could be dictated by estradiol status. We recently showed that exposure to high-linear energy transfer (LET) radiation resulted in a reduced latent period for, and enhanced progression of cataracts in rats that were 1 year old at the time of exposure compared to those that were 56 days old. However, the enhanced sensitivity of older lenses compared to younger lenses was independent of estradiol status. In the current study, we found that for 1-year-old rats exposed to 10 Gy of low-LET (60)Co γ rays, the rate of increase in the development of posterior and anterior subcapsular cataracts was higher in older ovary-intact rats compared to young rats. However, cataracts were detected much earlier in ovary-intact 56-day-old rats compared to 1-year-old rats, regardless of their treatment groups (ovary-intact, ovariectomized, or ovariectomized and implanted with capsules containing estradiol). Thus, despite a consistent estradiol response (potentiating effect of estrogen) within a given age group, the differences between the radiation response of old and young lenses cannot be accounted for solely by estradiol status.
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ovarian hormone modulation of radiation induced Cataractogenesis dose response studies
Investigative Ophthalmology & Visual Science, 2009Co-Authors: Robert M Bigsby, Shailaja Valluri, Marc S Mendonca, Jennifer T Lopez, Andrea Caperellgrant, Colleen Desrosiers, Joseph R DynlachtAbstract:PURPOSE. Epidemiologic data on the effects of female sex hormones in cataract formation are conflicting. With the use of a rat model of radiation-induced Cataractogenesis, it was found that estrogen can either enhance or inhibit the progression of radiation cataracts, depending on when the hormone is administered. The present study was performed to further define radiation-hormone interactions during Cataractogenesis. METHODS. In one experiment, rats were left ovary-intact or ovariectomized and were then irradiated with 2.5, 5, 10, or 15 Gy to one eye. In another experiment, ovariectomized rats were treated continuously with three different doses of estradiol through a slow-release capsule implanted subcutaneously, after which one eye was irradiated with 15 Gy. In all animals, cataract formation was followed by slit lamp examination at regular intervals. RESULTS. Latency to identification of cataracts decreased exponentially with increasing radiation dose. The presence of ovaries enhanced Cataractogenesis when the eye was irradiated with 15 Gy, but there was no difference between ovary-intact and ovariectomized rats that were irradiated at lower doses. In ovariectomized rats irradiated with 15 Gy, estradiol increased the rate of progression of cataracts in a dose-dependent manner. The rate of cataract progression increased linearly with increasing estradiol dose; there was no sign of saturation at high estradiol doses, as would be expected from a receptor-mediated effect. CONCLUSIONS. Ovarian hormones enhance radiation-induced cataract formation; hormone supplementation experiments indicate that estrogen is responsible for this effect. The data suggest that the enhancing effect of estradiol is not mediated by its receptor, but this requires further study.
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effect of gender on radiation induced Cataractogenesis
Radiation Research, 2009Co-Authors: Mark A Henderson, Shailaja Valluri, Marc S Mendonca, Jennifer T Lopez, Andrea Caperellgrant, Robert M Bigsby, Colleen Desrosiers, Christopher N Batuello, Eva Marie Powers, Joseph R DynlachtAbstract:Abstract Henderson, M. A., Valluri, S., DesRosiers, C., Lopez, J. T., Batuello, C. N., Caperell-Grant, A., Mendonca, M. S., Powers, E., Bigsby, R. M. and Dynlacht, J. R. Effect of Gender on Radiation-Induced Cataractogenesis. Radiat. Res. 172, 129-133 (2009). Radiation Cataractogenesis is an important consideration for radiotherapy patients and for astronauts. Data in the literature suggest that gender and/or estrogen may play a role in the incidence of age-related cataracts. However, few data exist on the effect of gender on radiation-induced Cataractogenesis. We compared the incidence and rate of progression of cataracts induced by ionizing radiation in male and female Sprague-Dawley rats. Male rats were implanted with either an empty silastic capsule or a capsule containing 17-β-estradiol. Ovary-intact female rats were implanted with empty capsules. All rats received a single dose of 10 Gy (60Co γ rays) to the right eye only. Lens opacification was measured at 2–4-week intervals with a slit lamp. The i...
Pitchairaj Geraldine - One of the best experts on this subject based on the ideXlab platform.
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structure based virtual screening and biological evaluation of a calpain inhibitor for prevention of selenite induced Cataractogenesis in an in vitro system
Journal of Chemical Information and Modeling, 2015Co-Authors: Arumugam Ramachandran Muralidharan, Chandrabose Selvaraj, Sanjeev Kumar Singh, Joen Rong Sheu, Philip A Thomas, Pitchairaj GeraldineAbstract:Calpains belong to the family of calcium-dependent, structurally related intracellular cysteine proteases that exhibit significant functions in evolution of different types of cataracts in human as well as animal models. Application of calpain inhibitors generated through a virtual screening workflow may provide new avenues for the prevention of Cataractogenesis. Hence, in the current study, compounds were first screened for potent calpain inhibitory activity by employing a structure-based approach, and the screening results were then validated through biological experiments in rat lenses. A hit compound, HTS08688, was obtained by structure-based virtual screening. A micromolar concentration of HTS08688 was found to prevent in vitro Cataractogenesis in isolated Wistar rat lenses, while maintaining the antioxidant and calcium concentrations at near normal levels. Inhibition of superoxide anion generation, as observed through cytochemical localization studies, and maintenance of structural integrity, as dem...
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Alterations in the lenticular protein profile in experimental selenite-induced Cataractogenesis and prevention by ellagic acid
Graefes Archive for Clinical and Experimental Ophthalmology, 2011Co-Authors: M Sakthivel, Pitchairaj Geraldine, Philip A ThomasAbstract:Background Accumulating evidence suggests that oxidative stress underlies age-related formation of cataract, and that antioxidants retard Cataractogenesis. This study aimed to evaluate whether ellagic acid, a natural polyphenol with antioxidant properties, prevents alterations in the lenticular protein profile in an experimental model of selenite cataract.
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prevention of selenite induced Cataractogenesis by rutin in wistar rats
Molecular Vision, 2009Co-Authors: M Isai, Philip A Thomas, E Ramesh, M Sakthivel, Pitchairaj GeraldineAbstract:Purpose: To investigate whether rutin retards selenite-induced Cataractogenesis in Wistar rat pups. Methods: On postpartum day ten, Group I rat pups received an intraperitoneal injection of saline. Group II and III rat pups received a subcutaneous injection of sodium selenite. Group III also received an intraperitoneal injection of rutin once daily on postpartum days 9–14. Both eyes of each pup were examined from day 16 up to postpartum day 30. After sacrifice, extricated pup lenses were analyzed for mean activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase. In addition, the mean concentrations of reduced glutathione (GSH) and of malondialdehyde were analyzed in samples of lenses and hemolysate. Results: There was dense lenticular opacification in all of Group II, minimal opacification in 33.3% of Group III, no opacification in 66.7% of Group III, and no opacification in Group I. Significantly lower mean activities of lenticular antioxidant enzymes were noted in Group II, compared to Group I and III. Significantly lower mean concentrations of GSH and higher mean concentrations of malondialdehyde were noted in samples of hemolysate and lens from Group II, compared to the values in Group I and III. Conclusion: Rutin prevents experimental selenite-induced Cataractogenesis in rat pups, possibly by preventing depletion of antioxidant enzymes and of GSH, and by inhibiting lipid peroxidation.
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the effect of acetyl l carnitine on lenticular calpain activity in prevention of selenite induced Cataractogenesis
Experimental Eye Research, 2009Co-Authors: R Elanchezhian, Pitchairaj Geraldine, M Sakthivel, Philip A ThomasAbstract:Abstract The present study sought to determine whether acetyl- l -carnitine (ALCAR) prevents selenite Cataractogenesis by mechanisms involving lenticular calpain activity, Wistar rat pups were divided into 3 groups of 15 each. Group I (normal) rats received an intraperitoneal (i.p.) injection of normal saline on postpartum day 10; Group II (cataract-untreated) rats received a single subcutaneous (s.c.) injection of sodium selenite (19 μmol/kg body weight) on postpartum day 10; Group III (cataract-treated) pups received a single s.c. injection of sodium selenite on postpartum day 10 and intraperitoneal injections of acetyl- l -carnitine (200 mg/kg body weight) on postpartum days 9–14. At the end of the study period (postpartum day 16), both eyes of each rat pup were examined by slit-lamp biomicroscopy. There was dense lenticular opacification in all Group II rats, minimal lenticular opacification in 33% of Group III rats, and no lenticular opacification in 67% of Group III and in all Group I rats. Group II lenses exhibited significantly lower mean values of calpain activity and Lp82 (lens-specific calpain) protein expression, decreases in relative transcript level of m-calpain mRNA and significantly higher mean Ca 2+ concentrations than Group I or Group III lenses; the values of these parameters in Group III rat lenses (ALCAR-treated) approximated those in Group I rat lenses. The results suggest that, in addition to its already-described antioxidant potential, ALCAR prevents selenite Cataractogenesis by maintaining calpain activity at near normal levels. These findings may stimulate further efforts to develop ALCAR as a novel drug for prevention of cataract.
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acetyl l carnitine prevents selenite induced Cataractogenesis in an experimental animal model
Current Eye Research, 2007Co-Authors: R Elanchezhian, Pitchairaj Geraldine, E Ramesh, M Sakthivel, M Isai, M Rajamohan, C Nelson A Jesudasan, Philip A ThomasAbstract:Purpose: To investigate whether acetyl-L-carnitine (ALCAR) retards selenite-induced Cataractogenesis in vivo. Methods: On postpartum day 10, group I pups received intraperitoneal saline and group II and group III pups received subcutaneous sodium selenite; Group III pups also received intraperitoneal ALCAR once daily on postpartum days 9–14. Both eyes of each pup were examined up to postpartum day 30. After sacrifice, extricated pup lenses were analyzed for antioxidant and redox system components. Results: There was dense lenticular opacification in all group II pups, minimal opacification in 33% of group III pups, and no opacification in 67% of group III and in all group I pups. Group II lenses exhibited significantly lower values of antioxidant and redox system components and higher malondialdehyde concentrations than group I or group III lenses. Conclusion: ALCAR prevents selenite-induced Cataractogenesis in Wistar rat pups, possibly by inhibiting depletion of antioxidant enzyme and redox system compon...
Robert M Bigsby - One of the best experts on this subject based on the ideXlab platform.
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age and hormonal status as determinants of Cataractogenesis induced by ionizing radiation i densely ionizing high let radiation
Radiation Research, 2012Co-Authors: Joseph R Dynlacht, Shailaja Valluri, Joy Garrett, Marc S Mendonca, Jennifer T Lopez, Andrea Caperellgrant, Robert M BigsbyAbstract:Age at the time of exposure to sparsely ionizing radiation has been established as a key determinant of radiation Cataractogenesis. However, while some reports suggest that the lenses of the young are hypersensitive, data from older studies are often conflicting and somewhat difficult to interpret when the radioresponse of young lenses is compared to that of adult lenses. Moreover, the mechanism of the age-response function for radiation Cataractogenesis has yet to be identified. Since steroid sex hormones, notably estradiol, appear to play a role in age-related Cataractogenesis, we hypothesized that the age response for radiation Cataractogenesis could be dictated by estradiol status. We recently showed that exposure to high-linear energy transfer (LET) radiation resulted in a reduced latent period for, and enhanced progression of cataracts in rats that were 1 year old at the time of exposure compared to those that were 56 days old. However, the enhanced sensitivity of older lenses compared to younger le...
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Age and hormonal status as determinants of Cataractogenesis induced by ionizing radiation. II. Sparsely ionizing (low-LET) radiation.
Radiation research, 2012Co-Authors: Joseph R Dynlacht, Shailaja Valluri, Joy Garrett, Colleen Desrosiers, Jessica Nees, Andrea Caperell-grant, Robert M BigsbyAbstract:Age at the time of exposure to sparsely ionizing radiation has been established as a key determinant of radiation Cataractogenesis. However, while some reports suggest that the lenses of the young are hypersensitive, data from older studies are often conflicting and somewhat difficult to interpret when the radioresponse of young lenses is compared to that of adult lenses. Moreover, the mechanism of the age-response function for radiation Cataractogenesis has yet to be identified. Since steroid sex hormones, notably estradiol, appear to play a role in age-related Cataractogenesis, we hypothesized that the age response for radiation Cataractogenesis could be dictated by estradiol status. We recently showed that exposure to high-linear energy transfer (LET) radiation resulted in a reduced latent period for, and enhanced progression of cataracts in rats that were 1 year old at the time of exposure compared to those that were 56 days old. However, the enhanced sensitivity of older lenses compared to younger lenses was independent of estradiol status. In the current study, we found that for 1-year-old rats exposed to 10 Gy of low-LET (60)Co γ rays, the rate of increase in the development of posterior and anterior subcapsular cataracts was higher in older ovary-intact rats compared to young rats. However, cataracts were detected much earlier in ovary-intact 56-day-old rats compared to 1-year-old rats, regardless of their treatment groups (ovary-intact, ovariectomized, or ovariectomized and implanted with capsules containing estradiol). Thus, despite a consistent estradiol response (potentiating effect of estrogen) within a given age group, the differences between the radiation response of old and young lenses cannot be accounted for solely by estradiol status.
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ovarian hormone modulation of radiation induced Cataractogenesis dose response studies
Investigative Ophthalmology & Visual Science, 2009Co-Authors: Robert M Bigsby, Shailaja Valluri, Marc S Mendonca, Jennifer T Lopez, Andrea Caperellgrant, Colleen Desrosiers, Joseph R DynlachtAbstract:PURPOSE. Epidemiologic data on the effects of female sex hormones in cataract formation are conflicting. With the use of a rat model of radiation-induced Cataractogenesis, it was found that estrogen can either enhance or inhibit the progression of radiation cataracts, depending on when the hormone is administered. The present study was performed to further define radiation-hormone interactions during Cataractogenesis. METHODS. In one experiment, rats were left ovary-intact or ovariectomized and were then irradiated with 2.5, 5, 10, or 15 Gy to one eye. In another experiment, ovariectomized rats were treated continuously with three different doses of estradiol through a slow-release capsule implanted subcutaneously, after which one eye was irradiated with 15 Gy. In all animals, cataract formation was followed by slit lamp examination at regular intervals. RESULTS. Latency to identification of cataracts decreased exponentially with increasing radiation dose. The presence of ovaries enhanced Cataractogenesis when the eye was irradiated with 15 Gy, but there was no difference between ovary-intact and ovariectomized rats that were irradiated at lower doses. In ovariectomized rats irradiated with 15 Gy, estradiol increased the rate of progression of cataracts in a dose-dependent manner. The rate of cataract progression increased linearly with increasing estradiol dose; there was no sign of saturation at high estradiol doses, as would be expected from a receptor-mediated effect. CONCLUSIONS. Ovarian hormones enhance radiation-induced cataract formation; hormone supplementation experiments indicate that estrogen is responsible for this effect. The data suggest that the enhancing effect of estradiol is not mediated by its receptor, but this requires further study.
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effect of gender on radiation induced Cataractogenesis
Radiation Research, 2009Co-Authors: Mark A Henderson, Shailaja Valluri, Marc S Mendonca, Jennifer T Lopez, Andrea Caperellgrant, Robert M Bigsby, Colleen Desrosiers, Christopher N Batuello, Eva Marie Powers, Joseph R DynlachtAbstract:Abstract Henderson, M. A., Valluri, S., DesRosiers, C., Lopez, J. T., Batuello, C. N., Caperell-Grant, A., Mendonca, M. S., Powers, E., Bigsby, R. M. and Dynlacht, J. R. Effect of Gender on Radiation-Induced Cataractogenesis. Radiat. Res. 172, 129-133 (2009). Radiation Cataractogenesis is an important consideration for radiotherapy patients and for astronauts. Data in the literature suggest that gender and/or estrogen may play a role in the incidence of age-related cataracts. However, few data exist on the effect of gender on radiation-induced Cataractogenesis. We compared the incidence and rate of progression of cataracts induced by ionizing radiation in male and female Sprague-Dawley rats. Male rats were implanted with either an empty silastic capsule or a capsule containing 17-β-estradiol. Ovary-intact female rats were implanted with empty capsules. All rats received a single dose of 10 Gy (60Co γ rays) to the right eye only. Lens opacification was measured at 2–4-week intervals with a slit lamp. The i...
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estrogen protects against radiation induced Cataractogenesis
Radiation Research, 2008Co-Authors: Joseph R Dynlacht, Shailaja Valluri, Marc S Mendonca, Jennifer T Lopez, Andrea Caperellgrant, Colleen Desrosiers, Falon Greer, Robert M BigsbyAbstract:Cataractogenesis is a complication of radiotherapy when the eye is included in the treatment field. Low doses of densely ionizing space radiation may also result in an increased risk of cataracts in astronauts. We previously reported that estrogen (17-β-estradiol), when administered to ovariectomized rats commencing 1 week before γ irradiation of the eye and continuously thereafter, results in a significant increase in the rate and incidence of cataract formation and a decreased latent period compared to an ovariectomized control group. We therefore concluded that estrogen accelerates progression of radiation-induced opacification. We now show that estrogen, if administered continuously, but commencing after irradiation, protects against radiation Cataractogenesis. Both the rate of progression and incidence of cataracts were greatly reduced in ovariectomized rats that received estrogen treatment after irradiation compared to ovariectomized rats. As in our previous study, estradiol administered 1 week prior to irradiation at the time of ovariectomy and throughout the period of observation produced an enhanced rate of cataract progression. Estrogen administered for only 1 week prior to irradiation had no effect on the rate of progression but resulted in a slight reduction in the incidence. We conclude that estrogen may enhance or protect against radiation Cataractogenesis, depending on when it is administered relative to the time of irradiation, and may differentially modulate the initiation and progression phases of Cataractogenesis. These data have important implications for astronauts and radiotherapy patients.
Philip A Thomas - One of the best experts on this subject based on the ideXlab platform.
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structure based virtual screening and biological evaluation of a calpain inhibitor for prevention of selenite induced Cataractogenesis in an in vitro system
Journal of Chemical Information and Modeling, 2015Co-Authors: Arumugam Ramachandran Muralidharan, Chandrabose Selvaraj, Sanjeev Kumar Singh, Joen Rong Sheu, Philip A Thomas, Pitchairaj GeraldineAbstract:Calpains belong to the family of calcium-dependent, structurally related intracellular cysteine proteases that exhibit significant functions in evolution of different types of cataracts in human as well as animal models. Application of calpain inhibitors generated through a virtual screening workflow may provide new avenues for the prevention of Cataractogenesis. Hence, in the current study, compounds were first screened for potent calpain inhibitory activity by employing a structure-based approach, and the screening results were then validated through biological experiments in rat lenses. A hit compound, HTS08688, was obtained by structure-based virtual screening. A micromolar concentration of HTS08688 was found to prevent in vitro Cataractogenesis in isolated Wistar rat lenses, while maintaining the antioxidant and calcium concentrations at near normal levels. Inhibition of superoxide anion generation, as observed through cytochemical localization studies, and maintenance of structural integrity, as dem...
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Alterations in the lenticular protein profile in experimental selenite-induced Cataractogenesis and prevention by ellagic acid
Graefes Archive for Clinical and Experimental Ophthalmology, 2011Co-Authors: M Sakthivel, Pitchairaj Geraldine, Philip A ThomasAbstract:Background Accumulating evidence suggests that oxidative stress underlies age-related formation of cataract, and that antioxidants retard Cataractogenesis. This study aimed to evaluate whether ellagic acid, a natural polyphenol with antioxidant properties, prevents alterations in the lenticular protein profile in an experimental model of selenite cataract.
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prevention of selenite induced Cataractogenesis by rutin in wistar rats
Molecular Vision, 2009Co-Authors: M Isai, Philip A Thomas, E Ramesh, M Sakthivel, Pitchairaj GeraldineAbstract:Purpose: To investigate whether rutin retards selenite-induced Cataractogenesis in Wistar rat pups. Methods: On postpartum day ten, Group I rat pups received an intraperitoneal injection of saline. Group II and III rat pups received a subcutaneous injection of sodium selenite. Group III also received an intraperitoneal injection of rutin once daily on postpartum days 9–14. Both eyes of each pup were examined from day 16 up to postpartum day 30. After sacrifice, extricated pup lenses were analyzed for mean activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase. In addition, the mean concentrations of reduced glutathione (GSH) and of malondialdehyde were analyzed in samples of lenses and hemolysate. Results: There was dense lenticular opacification in all of Group II, minimal opacification in 33.3% of Group III, no opacification in 66.7% of Group III, and no opacification in Group I. Significantly lower mean activities of lenticular antioxidant enzymes were noted in Group II, compared to Group I and III. Significantly lower mean concentrations of GSH and higher mean concentrations of malondialdehyde were noted in samples of hemolysate and lens from Group II, compared to the values in Group I and III. Conclusion: Rutin prevents experimental selenite-induced Cataractogenesis in rat pups, possibly by preventing depletion of antioxidant enzymes and of GSH, and by inhibiting lipid peroxidation.
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the effect of acetyl l carnitine on lenticular calpain activity in prevention of selenite induced Cataractogenesis
Experimental Eye Research, 2009Co-Authors: R Elanchezhian, Pitchairaj Geraldine, M Sakthivel, Philip A ThomasAbstract:Abstract The present study sought to determine whether acetyl- l -carnitine (ALCAR) prevents selenite Cataractogenesis by mechanisms involving lenticular calpain activity, Wistar rat pups were divided into 3 groups of 15 each. Group I (normal) rats received an intraperitoneal (i.p.) injection of normal saline on postpartum day 10; Group II (cataract-untreated) rats received a single subcutaneous (s.c.) injection of sodium selenite (19 μmol/kg body weight) on postpartum day 10; Group III (cataract-treated) pups received a single s.c. injection of sodium selenite on postpartum day 10 and intraperitoneal injections of acetyl- l -carnitine (200 mg/kg body weight) on postpartum days 9–14. At the end of the study period (postpartum day 16), both eyes of each rat pup were examined by slit-lamp biomicroscopy. There was dense lenticular opacification in all Group II rats, minimal lenticular opacification in 33% of Group III rats, and no lenticular opacification in 67% of Group III and in all Group I rats. Group II lenses exhibited significantly lower mean values of calpain activity and Lp82 (lens-specific calpain) protein expression, decreases in relative transcript level of m-calpain mRNA and significantly higher mean Ca 2+ concentrations than Group I or Group III lenses; the values of these parameters in Group III rat lenses (ALCAR-treated) approximated those in Group I rat lenses. The results suggest that, in addition to its already-described antioxidant potential, ALCAR prevents selenite Cataractogenesis by maintaining calpain activity at near normal levels. These findings may stimulate further efforts to develop ALCAR as a novel drug for prevention of cataract.
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acetyl l carnitine prevents selenite induced Cataractogenesis in an experimental animal model
Current Eye Research, 2007Co-Authors: R Elanchezhian, Pitchairaj Geraldine, E Ramesh, M Sakthivel, M Isai, M Rajamohan, C Nelson A Jesudasan, Philip A ThomasAbstract:Purpose: To investigate whether acetyl-L-carnitine (ALCAR) retards selenite-induced Cataractogenesis in vivo. Methods: On postpartum day 10, group I pups received intraperitoneal saline and group II and group III pups received subcutaneous sodium selenite; Group III pups also received intraperitoneal ALCAR once daily on postpartum days 9–14. Both eyes of each pup were examined up to postpartum day 30. After sacrifice, extricated pup lenses were analyzed for antioxidant and redox system components. Results: There was dense lenticular opacification in all group II pups, minimal opacification in 33% of group III pups, and no opacification in 67% of group III and in all group I pups. Group II lenses exhibited significantly lower values of antioxidant and redox system components and higher malondialdehyde concentrations than group I or group III lenses. Conclusion: ALCAR prevents selenite-induced Cataractogenesis in Wistar rat pups, possibly by inhibiting depletion of antioxidant enzyme and redox system compon...
Shailaja Valluri - One of the best experts on this subject based on the ideXlab platform.
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age and hormonal status as determinants of Cataractogenesis induced by ionizing radiation i densely ionizing high let radiation
Radiation Research, 2012Co-Authors: Joseph R Dynlacht, Shailaja Valluri, Joy Garrett, Marc S Mendonca, Jennifer T Lopez, Andrea Caperellgrant, Robert M BigsbyAbstract:Age at the time of exposure to sparsely ionizing radiation has been established as a key determinant of radiation Cataractogenesis. However, while some reports suggest that the lenses of the young are hypersensitive, data from older studies are often conflicting and somewhat difficult to interpret when the radioresponse of young lenses is compared to that of adult lenses. Moreover, the mechanism of the age-response function for radiation Cataractogenesis has yet to be identified. Since steroid sex hormones, notably estradiol, appear to play a role in age-related Cataractogenesis, we hypothesized that the age response for radiation Cataractogenesis could be dictated by estradiol status. We recently showed that exposure to high-linear energy transfer (LET) radiation resulted in a reduced latent period for, and enhanced progression of cataracts in rats that were 1 year old at the time of exposure compared to those that were 56 days old. However, the enhanced sensitivity of older lenses compared to younger le...
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Age and hormonal status as determinants of Cataractogenesis induced by ionizing radiation. II. Sparsely ionizing (low-LET) radiation.
Radiation research, 2012Co-Authors: Joseph R Dynlacht, Shailaja Valluri, Joy Garrett, Colleen Desrosiers, Jessica Nees, Andrea Caperell-grant, Robert M BigsbyAbstract:Age at the time of exposure to sparsely ionizing radiation has been established as a key determinant of radiation Cataractogenesis. However, while some reports suggest that the lenses of the young are hypersensitive, data from older studies are often conflicting and somewhat difficult to interpret when the radioresponse of young lenses is compared to that of adult lenses. Moreover, the mechanism of the age-response function for radiation Cataractogenesis has yet to be identified. Since steroid sex hormones, notably estradiol, appear to play a role in age-related Cataractogenesis, we hypothesized that the age response for radiation Cataractogenesis could be dictated by estradiol status. We recently showed that exposure to high-linear energy transfer (LET) radiation resulted in a reduced latent period for, and enhanced progression of cataracts in rats that were 1 year old at the time of exposure compared to those that were 56 days old. However, the enhanced sensitivity of older lenses compared to younger lenses was independent of estradiol status. In the current study, we found that for 1-year-old rats exposed to 10 Gy of low-LET (60)Co γ rays, the rate of increase in the development of posterior and anterior subcapsular cataracts was higher in older ovary-intact rats compared to young rats. However, cataracts were detected much earlier in ovary-intact 56-day-old rats compared to 1-year-old rats, regardless of their treatment groups (ovary-intact, ovariectomized, or ovariectomized and implanted with capsules containing estradiol). Thus, despite a consistent estradiol response (potentiating effect of estrogen) within a given age group, the differences between the radiation response of old and young lenses cannot be accounted for solely by estradiol status.
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ovarian hormone modulation of radiation induced Cataractogenesis dose response studies
Investigative Ophthalmology & Visual Science, 2009Co-Authors: Robert M Bigsby, Shailaja Valluri, Marc S Mendonca, Jennifer T Lopez, Andrea Caperellgrant, Colleen Desrosiers, Joseph R DynlachtAbstract:PURPOSE. Epidemiologic data on the effects of female sex hormones in cataract formation are conflicting. With the use of a rat model of radiation-induced Cataractogenesis, it was found that estrogen can either enhance or inhibit the progression of radiation cataracts, depending on when the hormone is administered. The present study was performed to further define radiation-hormone interactions during Cataractogenesis. METHODS. In one experiment, rats were left ovary-intact or ovariectomized and were then irradiated with 2.5, 5, 10, or 15 Gy to one eye. In another experiment, ovariectomized rats were treated continuously with three different doses of estradiol through a slow-release capsule implanted subcutaneously, after which one eye was irradiated with 15 Gy. In all animals, cataract formation was followed by slit lamp examination at regular intervals. RESULTS. Latency to identification of cataracts decreased exponentially with increasing radiation dose. The presence of ovaries enhanced Cataractogenesis when the eye was irradiated with 15 Gy, but there was no difference between ovary-intact and ovariectomized rats that were irradiated at lower doses. In ovariectomized rats irradiated with 15 Gy, estradiol increased the rate of progression of cataracts in a dose-dependent manner. The rate of cataract progression increased linearly with increasing estradiol dose; there was no sign of saturation at high estradiol doses, as would be expected from a receptor-mediated effect. CONCLUSIONS. Ovarian hormones enhance radiation-induced cataract formation; hormone supplementation experiments indicate that estrogen is responsible for this effect. The data suggest that the enhancing effect of estradiol is not mediated by its receptor, but this requires further study.
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effect of gender on radiation induced Cataractogenesis
Radiation Research, 2009Co-Authors: Mark A Henderson, Shailaja Valluri, Marc S Mendonca, Jennifer T Lopez, Andrea Caperellgrant, Robert M Bigsby, Colleen Desrosiers, Christopher N Batuello, Eva Marie Powers, Joseph R DynlachtAbstract:Abstract Henderson, M. A., Valluri, S., DesRosiers, C., Lopez, J. T., Batuello, C. N., Caperell-Grant, A., Mendonca, M. S., Powers, E., Bigsby, R. M. and Dynlacht, J. R. Effect of Gender on Radiation-Induced Cataractogenesis. Radiat. Res. 172, 129-133 (2009). Radiation Cataractogenesis is an important consideration for radiotherapy patients and for astronauts. Data in the literature suggest that gender and/or estrogen may play a role in the incidence of age-related cataracts. However, few data exist on the effect of gender on radiation-induced Cataractogenesis. We compared the incidence and rate of progression of cataracts induced by ionizing radiation in male and female Sprague-Dawley rats. Male rats were implanted with either an empty silastic capsule or a capsule containing 17-β-estradiol. Ovary-intact female rats were implanted with empty capsules. All rats received a single dose of 10 Gy (60Co γ rays) to the right eye only. Lens opacification was measured at 2–4-week intervals with a slit lamp. The i...
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estrogen protects against radiation induced Cataractogenesis
Radiation Research, 2008Co-Authors: Joseph R Dynlacht, Shailaja Valluri, Marc S Mendonca, Jennifer T Lopez, Andrea Caperellgrant, Colleen Desrosiers, Falon Greer, Robert M BigsbyAbstract:Cataractogenesis is a complication of radiotherapy when the eye is included in the treatment field. Low doses of densely ionizing space radiation may also result in an increased risk of cataracts in astronauts. We previously reported that estrogen (17-β-estradiol), when administered to ovariectomized rats commencing 1 week before γ irradiation of the eye and continuously thereafter, results in a significant increase in the rate and incidence of cataract formation and a decreased latent period compared to an ovariectomized control group. We therefore concluded that estrogen accelerates progression of radiation-induced opacification. We now show that estrogen, if administered continuously, but commencing after irradiation, protects against radiation Cataractogenesis. Both the rate of progression and incidence of cataracts were greatly reduced in ovariectomized rats that received estrogen treatment after irradiation compared to ovariectomized rats. As in our previous study, estradiol administered 1 week prior to irradiation at the time of ovariectomy and throughout the period of observation produced an enhanced rate of cataract progression. Estrogen administered for only 1 week prior to irradiation had no effect on the rate of progression but resulted in a slight reduction in the incidence. We conclude that estrogen may enhance or protect against radiation Cataractogenesis, depending on when it is administered relative to the time of irradiation, and may differentially modulate the initiation and progression phases of Cataractogenesis. These data have important implications for astronauts and radiotherapy patients.