Biochemical changes associated with selenite-induced cataract in the rat

Bunce, G. E.; Hess, John L.

doi:10.1016/s0014-4835(81)80125-x

Cited by 55 publications

(15 citation statements)

References 19 publications

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“…Its reliability and reproducibility result in a good rodent model for testing potential anticataract drugs. [1][2][3][4][5][6] Since Ostadalova et al 7 first introduced this model, numerous experiments have shown that both a single [8][9][10][11] or repeated subcutaneous injections of smaller doses of selenite, 12 and oral selenite administration 13 are cataractogenic. Selenite nuclear cataract appears within 3-5 days after a single injection of an overdose of sodium selenite.…”

Section: Introductionmentioning

confidence: 99%

Decreased chaperone activity of α-crystallin in selenite cataract may result from selenite-induced aggregation

Yan

Harding

Hui

et al. 2003

Eye

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Purpose To investigate the role of chaperone activity of a-crystallin in selenite-induced cataract formation. Methods Selenite cataract was induced in Sprague-Dawley rats by five subcutaneous injections of sodium selenite over a 20-day period starting at 8-10 days postpartum. a-Crystallin was separated from the rat lenses by size-exclusion chromatography. Bovine a L -crystallin and b L -crystallin were isolated for studies in vitro, and for the chaperone assays. The protective effects of both a H -and a L -crystallin were measured spectrophotometrically in four different assay procedures including the thermally induced aggregation of catalase and b L -crystallin, and the fructation-and heat-induced inactivation of catalase. The bovine a L -crystallin was incubated with different concentrations of sodium selenite for 72 h and then its chaperone activity against heat-induced b L -crystallin aggregation was assayed. The aggregation of selenite-treated a L -crystallin was analysed by molecular sieve high-performance liquid chromatography (HPLC). Results The protection of a H -crystallin was less than that of a L -crystallin in both normal and cataractous lenses. The chaperone activities of both a H -and a L -crystallin in selenite cataract were decreased compared with normal lenses. The protection provided by both a H -crystallin and a L -crystallin against the thermal aggregation of catalase was much greater than their protection against thermally and chemically induced inactivation. HPLC analysis demonstrated aggregation of a-crystallin by sodium selenite after 24 h incubation in a dose-dependent fashion. ConclusionThe chaperone activity of a-crystallin presented parallel patterns of activity with different methods, further supporting the view that the different assays measure essentially the same property. The decreased chaperone activity of a-crystallin in selenite cataract may result from seleniteinduced aggregation.

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Section: Introductionmentioning

confidence: 99%

Decreased chaperone activity of α-crystallin in selenite cataract may result from selenite-induced aggregation

Yan

Harding

Hui

et al. 2003

Eye

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“…The injection of sodium selenite at 3.28 mg/kg into 14-day-old rats resulted in very dense mature nuclear cataracts after 6 days (24,27,29). Animals that received the PSI, WR-77913, were protected against cataract induced by selenite ( Fig.…”

Section: Resultsmentioning

confidence: 94%

“…Selenite-induced opacity was associated with lenticular accumulation of calcium (24,25) rather than free-radical formation. Oxidation of protein sulfhydryls was observed in the late stages of cataract formation (24,26,27), although oxidation of epithelial cells may be important at earlier stages of cataract formation. The differences between the x-ray and selenite mechanisms make the selenite model an interesting test for the effectiveness of WR-77913 as a PSI in vivo.…”

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Phase-separation inhibitors and prevention of selenite cataract.

Clark

Steele

1992

Proc. Natl. Acad. Sci. U.S.A.

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The variation of the phase-separation temperature (Td) was studied in lenses during formation of cataracts induced by a subcutaneous ihfection of sodium selenite. In normal control animals, the Tc decreased monotonically with increasing age. Approximately 2 days after administration of the selenite the T, decreased sharply to a minimum, and then at day 4 the Tc increased dramatically toward body temperature. Mature irreversible cataracts formed -6 days after injection of the selenite. (18)(19)(20)(21). The effect of WR-77913 on x-ray cataract was not entirely unexpected because the amino phosphorothioates are believed to behave as free-radical scavengers (17). The inhibition of the x-ray cataract could be explained as protection against oxidative damage to lens cells caused by free radicals as well as an effect on T, (17,22).It was not anticipated that WR-77913 would prevent cataract produced by selenite. In contrast to the x-ray cataract, T, was reported to decrease rather than increase in the selenite cataract (23). Selenite-induced opacity was associated with lenticular accumulation of calcium (24, 25) rather than free-radical formation. Oxidation of protein sulfhydryls was observed in the late stages of cataract formation (24,26,27), although oxidation of epithelial cells may be important at earlier stages of cataract formation. The differences between the x-ray and selenite mechanisms make the selenite model an interesting test for the effectiveness of WR-77913 as a PSI in vivo. In this report we show a remarkable observation: the chemical inhibition of abnormal changes in Tc, in vivo, is sufficient for the effective prevention of selenite cataract in rats. While it is possible that the properties of WR-77913 as a PSI may have nothing to do with its mode of action in preventing selenite cataract, we present direct evidence that reagents acting in vivo on a cytoplasmic phase separation have the potential to control and prevent formation of cataract. was administered by intraperitoneal injection at a dose of 820 mg/kg 15 min prior to the injection ofPBS only (control group B) or sodium selenite (group D). At various times, upl to 9 days after treatments, animals from each group were euthanized. Lenses were removed and placed in silicone oil in the temperature-controlled sample chamber (see Fig. 2). The T" was measured immediately. MATERIALS AND METHODS

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“…A reduction in the activity or level of these antioxidants occurs in old age and causes cumulative damage that leads to formation of senile cataract (27) . Some studies suggest that selenite probably acts as an oxidative agent (28)(29) .…”

Section: Discussionmentioning

confidence: 99%