Influence of Selenife and Fourteen Trace Elementson Cataractogenesis in the Rot

Thomas R. Shearer, Ruth 5. Anderson, and Jim L. Brirron

The purposes of these experiments were to measure the influence of 14 trace elements on catarac-togenesis and to test if these trace elements could prevent cataracts induced by selenium. On days5-9 postpartum, suckling white rats received daily subcutaneous injections of either selenium (0.15pinoles Se, as Na2SeO3, per pup) or selenium plus one of 14 other trace elements (separate subcu-taneous injection) at one to five times the molar concentration of selenium. The frequency and severityof cataracts at three locations in the lens were assessed by slit-lamp examination on day 26-28postpartum. Seven ions were found to be effective in preventing selenium-induced cataracts (% pro-tection): mercuric (100%), silver (80%), cyanide (75%), arsenite (75%), cadmium (60%), and cupric(44%). Tellurite ion offered only 20% protection, while ferrous, zinc, lead, chromic, molybdate, tung-state, and vanadate ions provided no protection against selenium-induced cataract. No significantdifferences were found between the concentrations of selenium in the lenses of control and cataractouslenses when measured approximately three weeks after selenium injection. Except for selenium, noneof the trace minerals alone caused cataracts under our experimental conditions. In addition to sub-cutaneous injection of selenium, oral administration of this element was also found to cause cataract.It was concluded that among the ions studied, selinite was a powerful and rapid promoter of nuclearcataract formation, and that the protective ions may serve as useful probes for elucidating the mech-anism of selenium-induced cataracts. Invest Ophthalmol Vis Sci 24:417-423, 1983

Several laboratories have recently shown that in-jections of elevated quantities of the trace mineralselenium to rats during the suckling period causedthe formation of bilateral nuclear cataracts.1"4 Thesecataracts are interesting because of their speed of for-mation (3 days)4 and because they may be usefulmodels for cataracts caused by oxidant stressors. Se-lenium-induced cataracts have been characterizedhistologically,' and several important biochemicalchanges have been noted. For example, glutathioneand proteinaceous sulfhydryl levels were decreased,4while the ratio of insoluble to soluble proteins andH2O2 were increased in lenses of rats with selenium-induced cataract5. Hess et al6 recently reported changesin specific peptides in the soluble and insoluble len-

From the Departments of Biochemistry and Ophthalmology,The Oregon Health Sciences University, Portland, Oregon.

Presented in part at the Annual Meeting of the Association forResearch in Vision and Ophthalmology, Sarasota, Florida, May1982.

Supported by NIH grant EY-3600 from the National Eye In-stitute and by the R. Blaine Bramble Medical Research Founda-tion.

Submitted for publication June 17, 1982.Reprint requests: Thomas R. Shearer, PhD, Departments of

Biochemistry and Ophthalmology, The Oregon Health SciencesUniversity, Portland, OR 97201.

ticular proteins from rats receiving selenium. Sele-nium is also noted for its interaction with other traceminerals,7 and we recently reported that cadmiumameliorated the frequency of selenium-induced cat-aract.8 However, the lens contains a variety of othertrace minerals,9 yet it is not known if other trace ele-ments modify selenium-induced cataracts. Most ofthe selenium taken in by man is from the diet, yetthere is no evidence on whether or not oral admin-istration of selenium is cataractogenic. Thus, the pur-poses of the experiments described below were: (1)to compare 14 trace elements to selenium in theirabilities to promote cataract in the animal model,(2)to determine if other trace elements ameliorate se-lenium-induced cataract, and (3) to determine if oraladministration of selenium promotes cataract for-mation.

Materials and MethodsInjection Experiments

Nineteen Sprague-Dawley derived, albino femalerats (Simonsen Laboratories, Inc., Gilroy, CA) withtheir litters of pups were individually housed in poly-propylene breeding cages with cellulose bedding ma-terial. The animals received laboratory chow (WayneLab Blox, F-6, Continental Grain Co., Chicago, IL)

0146-0404/83/0400/417/$ 1.15 Association for Research in Vision and Ophthalmology

417

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418 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / April 1983 Vol. 24

Table 1. Cataractogenesis by seleniteand other trace minerals

Element

SeleniumTelluriumArsenicMolybdenumTungstenVanadiumCyanideZincIronLeadCadmiumCopperSilverChromiumMercury

Ionicform

SeO3=

TeO-TAsO2"MoO4"WO4"VO3=CN"Zn++Fe++Pb+ +Cd++Cu++Ag+Cr+3Hg++

Compoundinjected

Na2SeO3K2TeO3NaAsO2Na2MoO4Na2WO4NH4VO3KCNZnCl2FeCl2Pb(C2H3O2)2CdCl2Cu(C2H3O2)2AgNO3CrCl3HgCl2

Dosage(fimoles

element/rat)0.150.150.300.300.300.300.300.760.450.300.300.300.300.300.15

Frequencyof cataract(percent)

10000000000000000

and distilled water ab libitum. The animal room waslight (12-hr fluorescent) and temperature (~72) con-trolled.

On days 5 through 9 postpartum, the suckling pupsreceived daily 0.05 ml subcutaneous injections of ei-ther: (1) saline (controls), (2) selenium or one of the14 other ions shown in Table 1, or (3) selenium atone site on the back, and, usually within 5 min, oneof the other ions at a separate site on the back. Thedosage of selenium given was 0.15 jtimoles Se per pupper day, which averaged approximately 0.70 mgSe/kg b.w. per day over the 5 days of the injections.Other ions were given at one to five times the dosagelevel of selenium on a molar basis (Table 1) depend-ing on the toxicity of the element. All chemicals in-jected into the animals were labeled either "reagentgrade" or "chemically pure" except for potassiumtellurite (Sigma), which was not graded but was 98%pure.

A single injection experiment was also performedin which suckling pups received single 0.05-ml sub-cutaneous injections of selenium and cadmium onlyon day 10 postpartum. One group of nine animalsreceived 0.42 /tmoles of selenium per pup, while asecond group of eight animals received 0.42 ^molesselenium per pup at one injection site on the backand 0.42 t^moles of cadmium per pup at another in-jection site on the back.Oral Dosage Experiments

Four Sprague-Dawley derived, COB albino femalerats (Charles River, Wilmington, MA) with their lit-ters of pups were housed as described above. On days6 through 10 postpartum, the suckling pups receiveddaily 0.01 ml 0.5 M glucose solutions containing ei-

ther nothing (controls), or 0.11, 0.23, or 0.46 ^molesSe, as Na2Se03, per pup per day. The solutions weregently placed in the oral cavity with a micropipetter(Labsystems, Helsinki, Finland). The animals readilyswallowed the solutions, and none dribbled out oftheir mouths.

The eyes were dilated with a 1:1 solution of 10%phenylephrine hydrochloride (Smith, Miller, andPatch) and 1% atropine (Isopto Atropine, Alcon) andexamined with a photographic slit lamp (Zeiss, WestGermany). A numerical scoring system was used tograde three areas of the lens. The central area of thenucleus and the peripheral area surrounding the nu-cleus were scored:

0 = Clear;1+ = Shadowy dust-like opacities, occasionally

with some very small, dense particles;2+ = Definite opacity, but transmitted consider-

able light;3+ = Almost total opacity, transmitted small

amount of light;4+ = Totally opaque.

Swollen lenticular fibers were scored:0 = Not visible;

1+ = Visible;2+ = Pronounced;3+ = Fibers seemed separated.The lens cortex was checked for vacuoles and

changes in density, but it was not assigned a numer-ical score.

At the termination of the experiment, the lenseswere dissected from enucleated eyes, weighed andanalyzed for selenium by a fluorometric method.21This method involved wet digestion of the lenses ina boiling mixture of nitric, sulfuric, and perchloricacids, complexation with 2, 3 diaminonapthalene re-agent, and fluorescence determination.

Results

Cataractogenesis by Selenium

Injections of 0.15 ^moles of selenium as sodiumselenite on days 5-9 postpartum caused bilateral nu-clear cataracts to form in all animals. Slit-lamp ex-amination showed that central nuclear area to be veryopaque (3+ to 4+), and this area was often lobed orangular in shape (Fig. 1 A). The area surrounding thecentral opacity was spherical and showed diffuseopacity (1+ to 2+). This peripheral nuclear area usu-ally showed the same degree of density throughout,but occasionally there were 4+ particles scattered init. At the margin between the peripheral nuclear areaand the lens cortex, a spoke-like pattern of swollen

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No. 4 5ELENITE AND TRACE ELEMENTS IN CATARACT / Shearer er al. 419

lens fibers was seen, and these swollen fibers appearedto meet at the Y suture. At this dosage level of se-lenium, the cortex of the lenses containing nuclearcataracts did not have opacities, but differences inrefraction appearing as dense rings were observed inthe outer cortex. The lenses of control animals re-ceiving saline were clear.

Oral administration of selenium also caused cat-aract formation (Fig. IB). On day 6 to 10 postpartum,these rats received selenium in 0.01 ml of 0.5 M glu-cose solution that was placed in the oral cavity of theanimals. At levels of 0.23 jumoles Se and above, allanimals developed bilateral nuclear cataracts (Table2). The cataracts formed were similar in appearanceand severity (Table 2) to those described above forrats receiving selenium by injection. Also note thatthe dosage level of selenium needed to cause cataractswhen given orally (0.23 /^moles/rat) was similar tothat needed to cause cataracts by injection (0.15Mmoles/rat).

Lack of Cataractogenesis by Other Trace Minerals

Fourteen other ions were tested for their ability toproduce cataracts at the dosage levels shown in Table1 using the same experimental protocol that producedcataractogenesis with injected selenite. Careful ex-amination with the slit lamp revealed no significantopacities or vacuoles in the animals (Table 1). Threeof the ten animals receiving 0.76 yumoles of zincshowed very mild opacities scoring 1 +, but these werenot observed in a repeat experiment.

Protection Against Selenium-induced Cataract byOther Trace Elements

Injections of trace elements along with seleniuminfluenced the frequency of selenium-induced cata-ract. Tellurium was minimally effective in protectingagainst selenium-induced cataract since 80% of theanimals receiving tellurium injections along with se-lenium injections developed cataracts (Table 3). The20% of the animals that were cataract free had noevidence of cataract as seen by careful examinationwith the slit lamp. Copper and cadmium were mod-erately effective in prevention of selenium-inducedcataract since only 56% and 40%, respectively, of theselenium animals receiving these trace minerals de-veloped cataract. Arsenic, cyanide, and silver ionswere very effective since only 20 to 25% of the animalsreceiving these elements along with selenium devel-oped cataracts. The cataracts that did develop inrats receiving both selenium and competing ions hadthe typical features of selenium-induced cataract(Fig. 1C).

Fig. 1. Slit-lamp photographs of eyes of rats with selenium-in-duced cataract. A, Approximately 3 weeks after suckling rat pupreceived subcutaneous injections of 0.15 umoles Se on days 5-9postpartum. The central nucleus was opaque and the peripheralnucleus showed diffuse opacity (asterisk). B, Nuclear cataract inlens of animal receiving oral selenium, C, Eye of rat receivingsimultaneous injections of selenium and copper.

The most effective trace element studied for pre-vention of selenium-induced cataract was mercuricion (Table 3). At dosage levels equal to selenite, mer-

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420 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / April 1983 Vol. 24

Table 2. Influence of oral selenite on cataractogenesis

Parameter

Body weight (g)Mortality (%)Frequency of cataract

AnimalsPercent

Cataract opacity scoreCentral nucleusPeripheral nucleusSwollen fibers

0.0

96 2(10)*0

0/100

Clear (10)Clear(10)

Absent

Dosage fomoles Se/rat)0.11

91 2(10)0

0/100

Clear (10)Clear (10)

Absent

0.23

96 2 (9)0

10/10100

3.5 0.2 (9)1.3 0.2 (9)1.8 0.3 (9)

0.46

69 6 (7)30

7/7100

Hypermature (6)Hypermature (6)Hypermature (6)

* Mean SE (number of animals) on day 27 post partum.

cury was totally effective in preventing selenium-in-duced cataract formation. Further titration of themercury dosage to half the molar level of selenium(0.075 /imoles Hg per rat) still prevented cataract for-mation in 70% of the animals receiving selenium.

Zinc, iron, lead, chromium, molybdenum, tung-state, and vanadium had no influence on the fre-quency of selenium-induced cataract (Table 4). Thisoccurred despite the fact that the levels of these traceminerals administered were two to five times the dos-age level of selenium.

The data in Table 5 show the influence of protec-tive trace minerals on the severity of selenium-in-duced cataract. Selenium alone caused very densecataract formation in the nucleus, resulting in an av-erage nuclear score of 3.9. The peripheral nucleus wasonly mildly involved, with an average score of 1.1.Swollen fibers scored an average of 1.9 (pronounced).The protective ions tellurium, copper, cadmium, ar-senic, cyanide, and silver all tended to reduce theseverity of selenium-induced cataracts (Table 5).Opacity scores in the central nucleus, peripheral nu-cleus, or swollen fibers tended to be lower in animalsreceiving these ions along with selenium. The sele-nium plus mercury group could not be scored because

Table 3. Trace elements protective against

mercury completely protected against cataract for-mation.

Similar to the frequency studies, the nonprotectivetrace minerals zinc, iron, chromium, molybdenum,tungsten, vanadium, and lead were ineffective in re-ducing the severity of selenium-induced cataract.Scores in the central and peripheral nuclear areas ofthese cataracts were similar to the animals receivingonly selenium, while the scores for the presence ofswollen fibers were actually increased in the groupsreceiving lead and zinc. Tungstate may have poten-tiated the severity of selenium-induced cataracts sincecortical opacities were observed.

Neither selenium nor selenium plus the other pro-tective ions caused any changes in the weights oflenses measured at the termination of the multipleinjection experiments (Table 6). The average concen-tration of selenium in the lenses of control rats was0.53 ppm Se (Table 6). In rats receiving seleniuminjections alone, lens selenium concentrations were0.63 ppm Se, and this value was not statistically dif-ferent from controls. Likewise, there were no obviouschanges in the concentrations of selenium measuredin the lenses of animals receiving selenium plus othertrace minerals.

Table 4. Trace minerals not protective againstSe-induced cataract

se-inauc

Group

SeSe + TeSe + CuSe + CdSe + AsSe + CNSe + AgSe + Hg

ea cataractTrace mineral

Dosage (\imoleselement/rat)

0.150.150.300.300.300.300.300.15

Form

SeO3=TeO3=Cu++Cd++AsO2"Cn"Ag+Hg++

Frequency oj cataractAnimals

44/448/105/94/102/82/82/100/10

Percent

1008056402525200

Group

SeSe + ZnSe + FeSe + PbSe + CrSe + MoSe + WSe + V

Trace mineral

Dosage (^moleselement/rat)

0.150.760.450.300.300.300.300.30

Form

SeO3=Zn+ +Fe++Pb+ +Cr+3Mo

No. 4 SELENITE AND TRACE ELEMENTS IN CATARACT / Shearer er al. 421

The studies presented above provided trace min-erals in daily injections over a 5-day period. In an-other experiment, similar to previous studies,2"5 wefound that a single injection of 0.42 /umoles Se onday 10 postpartum caused cataract formation in 90%of the injected animals, and the average opacity scorefor the central nucleus was 4.0 0 (9). Cataracts weregenerally observable as soon as the eyes opened (14days postpartum). A second group of animals receiv-ing a single injection of 0.42 jumoles of Cd along withthe single injection of 0.42 ^moles Se showed a mark-edly decreased frequency (38%) and severity of cat-aract (central nucleus opacity score: 1.3 0.33).

DiscussionThe data presented above emphasized two facets

of trace mineral-induced cataractogenesis: (1) com-pared to 14 other trace elements, selenium was a po-tent and extremely rapid promoter of cataracts; and(2) the data also pointed out the rather dramatic in-fluence trace element interactions can have on cat-aractogenesis.

Regarding the comparative strength of seleniumin promoting cataracts, we attempted to inject asmuch of the other trace minerals so that dosage levelswere equimolar or greater than selenium, yet so asnot to exceed moderate toxicity levels of the elements.Mercury and tellurium could be reasonably toleratedonly at levels equimolar to selenium. The animals inthe groups receiving zinc, iron, lead, silver, copper,cyanide, arsenic, cadmium, chromium, molybde-num, tungsten, and vanadium received from two tofive times the dosage level of selenium. Despite thesehigher dosages, none of the animals receiving theseelements alone showed any form of significant cat-aract at 27 days postpartum. On the other hand, 100%of the animals receiving selenium developed verydense bilateral nuclear cataracts that were visible assoon as the eyes opened. It is possible that the otherelements could have produced cataracts under morelong-term exposure or after a longer latent period.However, the data serve to emphasize how potentselenium is in promoting cataract in a short periodof time.

Other investigators have reported that a single in-jection of selenium on day 10 postpartum will pro-mote nuclear cataract formation in the rat, and thatthe rabbit and guinea pig are also susceptible to thiscataract.2"4 Our present slit-lamp study revealed thatseveral other lenticular changes can be present alongwith the obvious central nuclear opacity. A less densenuclear opacity was observed surrounding the centralnuclear cataract, and a single layer of a spoke-likepattern of swollen lenticular fibers extended around

Table 5. Influence of protective trace elements onseverity of Se-induced cataract

Group

SeSe + TeSe + CuSe + CdSe + AsSe + CNSe + AgSe + Hg

Cataract opacity score

Central nucleus

3.9 0.04 (29)*2.9 0.4 (8)2.2 0.6 (5)3.6 0.4 (4)2.0 1.0(2)2.0 1.0(2)4.0 0.0 (2)

0

Peripheralnucleus

1.1 0.10.8 0.30.6 0.20.3 0.10.3 0.31.0 1.0 (0.0 0.0

0

Swollenfibers

.9 0.1

.6 0.2

.4 0.7

.3 0.3

.0 1.0).8 0.3.5 0.5

0

* Mean SE (number of animals with cataracts in a group).

the peripheral nuclear opacity to the Y suture. Trans-mission electron microscopy of lens fibers from se-lenium-induced cataracts showed no changes in theapposition of one fiber to another, but rather exten-sive vacuolization of the cytoplasm within the fi-bers.10 Although the data presented in this report didnot show an increase in overall wet weight of sele-nium treated lenses (Table 6), other studies5 usinghigher dosages of selenium showed a significant in-crease in the water content of hypermature cataracts.Extensive vacuolization of the lens cortex was alsonoted in a previous study where high doses of sele-nium were repeatedly injected over many days.1These data may indicate that selenium cataract in-terferes with the normal functioning of the cationpump, but this is speculation at the present time.

Another interesting feature of selenium-inducedcataracts is the fact that nuclear cataracts appearwithin 3 to 4 days after selenium injection.4 Ob-viously, cells undergoing differentiation and apposi-tional growth at the lens bow at the time of seleniuminjection would not have sufficient time to migrate

Table 6. Selenium concentrations and wet weightsof lenses after multiple injections of protectivetrace elements with selenite

Group

ControlSeSe + TeSe + CuSe + CdSe + AsSe + CNSe +AgSe + Hg

Wet

202022192121202121

weight (mg)

1 (3)* 1 (3) 1 (3)2(3)0(3) 1(3) 0 ( 3 ) 1(3) K3)

Lens

Selenium (ppm)

0.53 0.03 (3)0.63 0.04 (3)0.78 0 .15 (3)0.65 0 .15 (3)0.56 0 .16 (3)0.66 0.09 (3)0.57 0 .11 (3)0.57 0.06 (2)0.56 0.06 (3)

* Mean SE (n = pool of lenses). Each pool usually consisted of fourlenses that were collected 19-21 days after the last selenium injection.

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422 INVESTIGATIVE OPHTHALMOLOGY 6 VISUAL SCIENCE / April 1983 Vol. 24

into the nuclear region and form a cataract. Fur-thermore, studies using cataractous doses of seleniumtagged with 75Se indicate that there is very little 75Seactually in the nuclear cataract.* These data indicatethat the site of action of selenium is extrinsic to thenuclear cataract itself.

It should be noted that the ability of selenium toinduce cataract is dependent on the age of the animal.After 18 days postpartum, selenium injections no lon-ger cause permanent cataracts in rats.2 Why the sen-sitivity of the lens to selenium changes with time isunknown, but investigations into this subject wouldbe useful since they may help pinpoint the biochem-ical basis for selenium-induced cataract.

Although the data in Table 6 showed no statisti-cally significant increases in the selenium content oflenses of animals receiving selenium injection, thesedata should not be interpreted as showing that thelens does not take up some selenium. Besides theanalytical variability in measuring small levels of se-lenium in the lens, the data may be misinterpretedbecause selenium was measured almost 3 weeks afterthe last selenium injection. Two other reports419 in-dicated that after a single injection of selenium, lensselenium levels peak 6-24 hr postinjection, and75Se levels fall rapidly in the lens thereafter.* Thecritical time period for cataract formation from se-lenium is probably within the first 3-4 days after in-jection. Future studies could test if some of the pro-tective ions influence lens selenium levels at theseearly time periods.

The biochemical mechanism of action of seleniumin cataract promotion may be related to the affinityof selenite for sulfhydryl groups. Selenium in othersoft and hard tissues of the body is associated withproteins, as selenoamino acids (ie, selenocysteine)and as selenotrisulfides (R-S-Se-S-R).'' Selenotrisul-fides are reduced further to selenopersulfides (R-Se-H) by glutathione reductase and by excess reducedglutathione, as is found in the lens. Selenite causesthe nonenzymatic oxidation of sulfhydryl groups toform disulfides and selenotrisulfides.4'11 Two reportsdescribed reduced levels of sulfhydryl groups in se-lenium-induced cataracts.4'5 It has been proposed thatselenite is cataractogenic by causing the formation ofcataractous disulfide linkages in lens proteins.5 How-ever, we recently found that total lens disulfides werenot increased in selenite cataract. This does not ex-clude the possibility of disulfide formation in certainclasses of proteins or at specific anatomical sites.

The survey of 14 trace minerals in the present studyrevealed six elements that offered significant protec-

* Shearer TR and Britton JL: Unpublished data.

tion against selenium-induced cataract. Equimolaramounts of mercury were totally effective in pre-venting selenium-induced cataracts, while silver, cy-anide, arsenic, cadmium, and copper were partiallyprotective when injected at two times the level ofselenium. Interaction between mercury and seleniumin other soft tissues is reported to be due to the for-mation of mercury-selenium complexes that arethought to be less toxic than the separate ionic speciesof these elements.12 The binding constant for mercuryto sulfhydryl groups is high.21 Mercury may preventselenium cataracts by complexing with selenium orby blocking uptake of selenium onto critical sulfhy-dryl groups.

Copper, silver, and cyanide are also known to formcomplexes with selenium and to mutually alleviatetoxicity symptoms.12"14 Arsenite is known to increasethe secretion of selenium into bile, where the sele-nium is bound to protein and glutathione sulfhydrylgroups.15 Cadmium diverts selenium from low mo-lecular weight complexes to high molecular weightcomplexes.16 It should also be noted that with regardto cadmium, the results with the single injectionmodel were similar to those for the multiple, 5-dayinjection model. Common features of all the protec-tive elements were that they either complex with se-lenium directly or altered the normal metabolism ofselenium.

Tellurium was interesting because it is the nextelement below selenium in the periodic table, and itmay be metabolized by reductive pathways as is se-lenium.17 However, simultaneous injection of equi-molar amounts of tellurium (0.15 ^ moles/pup) pre-vented only 20% of selenium-induced cataracts. Ina separate experiment where no selenium was in-jected, animals were given a very toxic dose of 0.30/imoles tellurium/pup. Three of the six surviving ratsdeveloped only a very mild (1+) nuclear opacity.Thus, tellurium was neither a good competitor of se-lenium for cataract prevention nor was tellurium veryeffective in promoting cataract, again indicating thepotency of selenium in cataract formation evenamong members of the same group in the periodictable.

Per kilogram of body weight, the amounts of se-lenium and other trace elements administered inthese animal experiments was much higher thanthose consumed by man.18 However, we feel that se-lenium-induced cataracts are a useful animal modelfor a cataract formation for several reasons: (1) se-lenium-induced cataracts are a model of cataractscaused by an oxidant stressor, in this case seleniteion. (2) The data in the present communication arethe first demonstration that oral administration ofselenium was cataractogenic. The cataracts were sim-

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No. 4 SELENITE AND TRACE ELEMENTS IN CATARACT / Sheorer er ol. 423

ilar to those produced by the injection model, andthe data indicate that this more physiologic route ofselenium ingestion was cataractogenic. (3) The pro-tective ions Hg, Ag, CN, As, Cd, Cu, and Te may beuseful probes for studying the mechanism of actionof selenium and similar cataractic agents. (4) Futureexperiments with this animal model might test theinteraction of selenium with subacute amounts ofother cataractogenic agents such as x-ray radiationor altered blood sugars. Bhuyan19 recently reportedstatistically significant increases in the selenium con-centrations of human cataractous lenses. Also, wewonder if continuous exposure to somewhat elevatedquantities of dietary selenium might be interactivewith other environmental agents and thereby predis-pose man to cataract.

Key words: selenite, trace elements, cataract, rat, slit lamp

Acknowledgments

The authors wish to express appreciation to Dr. EarlPalmer and Mr. Pat Wallace for help with the slit-lampbiomicroscopy, and to Dr. Jack Fellman for helpful dis-cussions.

References

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2. Ostadalova I, Babicky A, and Obenberger J: Cataractogenicand lethal effect of selenite in rats during postnatal ontogenesis.Physiol Bohemoslov 28:393, 1979.

3. Bhuyan KC, Bhuyan DK, and Podos SM: Selenium-inducedcataract and its possible biochemical mechanism. In Seleniumin Biology and Medicine, Second International Symposium,Spallholz JE, editor. Westport Conn. AVI Publishing, 1981.

4. Bunce GE and Hess JL: Biochemical changes associated withselenite-induced cataract in the rat. Exp Eye Res 33:505, 1981.

5. Bhuyan KC, Bhuyan DK, and Podos SM: Cataract inducedby selenium in the rat: I. Effect on the lenticular protein andthiols. II. Increased lipid peroxidation and impairment of en-zymatic defense against oxidative damage. IRCS Med Sci: TheEye 9:194; 195, 1981.

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9. Swanson AA and Truesdale AW: Elemental analysis in normaland cataractous human lens tissue. Biochem Biophys ResCommun 45:1488, 1971.

10. Russell NJ, Britton JL, and Shearer TR: Transmission electronmicroscopy and selenium concentrations in selenium-inducedcataract. (Abstract 1511) Fed Proc 41:529, 1982.

11. Levander OA: Selected aspects of the comparative metabolismand biochemistry of selenium and sulfur. In Trace Elementsin Human Health and Disease. Vol. II. Essential and ToxicElements, Prasad AS, editor. New York, Academic Press,1976, pp. 135-163.

12. Ganther HE: Interactions of vitamin E and selenium withmercury and silver. Ann NY Acad Sci 355:212, 1980.

13. Hill CH: Mineral interrelationships. In Trace Elements inHuman Health and Disease. Vol. II. Essential and Toxic Ele-ments, Prasad AS, editor. New York, Academic Press, 1976,pp. 281-300.

14. Palmer IS and Olson OE: Partial prevention by cyanide ofselenium poisoning in rats. Biochem Biophys Res Commun90:1379, 1979.

15. Alexander J: The influence of arsenite on the interaction be-tween selenite and methyl mercury. Dev Toxicol Environ Sci8:585, 1980.

16. Whanger PD, Ridlington JW, and Holcomb CL: Interactionof zinc and selenium on the binding of cadmium to rat tissueproteins. Ann NY Acad Sci 355:333, 1980.

17. Venugopal B and Luckey TD: Toxicity of group VI metalsand metaloids. In Metal Toxicity in Mammals. 2. ChemicalToxicity of Metals and Metalloids, Luckey TD and VenugopalB, editors. New York, Plenum Press, 1978, pp. 233-259.

18. Committee on Medical and Biologic Effects of EnvironmentalPollutants, National Research Council: Selenium. Washing-ton, D.C. National Academy of Sciences, 1976, pp. 9-27.

19. Bhuyan KC, Baxter T, and Morris JS: Selenium status in theeye: Increased level in cataract in the human and its distri-bution in eye tissues of animals. ARVO Abstracts. InvestOphthalmol Vis Sci 22(Suppl):35, 1982.

20. Hoffman I, Westerby RJ, and Hidiroglou M: Precise fluoro-metric microdetermination of selenium in agricultural mate-rial. J Assoc Off Anal Chem 51:1039, 1968.

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