8/18/2019 Human Kidney versus rat kidney

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VME 6602 Homework 1

 The physiological diferences between humans and laboratory rats can be important

when it comes to studying enobiotic metabolites that may be the inducers o!

undesired side efects" #s an eample$ the kidneys !unction to eliminate waste

products !rom the bloodstream$ but rats produce a more concentrated urine thanhumans %&ad ' (henglis$ 1))*+" This concentrated urine will lead to an increased

concentration o! all solutes including undesired metabolic products" #ssuming the

metabolism o! the original compounds and distribution o! the metabolites is similar

between rats and humans$ the parent compound would appear to ha,e a lower

obser,able ad,erse efect le,el %-#E.+ than it truly has in humans" -n the one

hand$ this may be bene/cial !or en,ironmental eposure minimiation since it

beha,es like a built in sa!ety !actor" -n the other hand$ this may be an undesired

efect when per!orming drug studies humans may be able to tolerate a higher$

possibly more efecti,e dose o! a medication"

(yclamate is an arti/cial sweetener that was associated with the de,elopment o!bladder cancer in laboratory rats$ but this same association was not seen in human

epidemiological studies %ational (ancer 3nstitute$ 200)+" The physiological

diference in the concentrability o! urine could be a simple eplanation !or the

obser,ed diferences !or de,eloping bladder cancer" The micro4ora o! the intestinal

tract con,ert cyclamate %the nontoic parent compound+ to cycloheylamine %the

toic5efect inducing metabolite+$ and both human and rat intestinal tissues will

readily absorb the cycloheylamine$ which enters the bloodstream be!ore it is

/ltered out by the kidneys %rasar et al"$ 1)*2+" 7ased on this obser,ation$ the rats

will ha,e a higher dose o! cycloheylamine controlled !or the eposed sur!ace area

in the bladder and storage time resulting in an increased risk o! de,eloping

bladder cancer o,er time"

8e!erences

1" rasar 79$ 8enwick #&$ :illiams 8T" The role o! the gut 4ora in the

metabolism o! cyclamate" 7iochem ;" 1)*2??15)0"2" &ad 9($ (henglis (@" #cute Toicology Testing" 1))* #cademic @ress" p A=="A" ational (ancer 3nstitute" http>BBwww"cancer"go,Babout5cancerBcauses5

pre,entionBriskBdietBarti/cial5sweeteners5!act5sheet #ug )$ 200)" %#ccessed

01511516+

http://www.cancer.gov/about-cancer/causes-prevention/risk/diet/artificial-sweeteners-fact-sheethttp://www.cancer.gov/about-cancer/causes-prevention/risk/diet/artificial-sweeteners-fact-sheethttp://www.cancer.gov/about-cancer/causes-prevention/risk/diet/artificial-sweeteners-fact-sheethttp://www.cancer.gov/about-cancer/causes-prevention/risk/diet/artificial-sweeteners-fact-sheet