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Title: Alternative Sweeteners

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Stevioside 179<br />

side given as an infusion up to 16 mg/kg body weight/hr was found to be secreted<br />

by way of the renal tubular epithelium to induce a fall in the renal tubular reabsorption<br />

of glucose (39). The effect of stevioside (90% purity; 16 mg/kg body<br />

weight/hr infusion) on renal function in both normal and hypertensive rats was<br />

investigated using clearance techniques, and, in an analogous fashion to S. rebaudiana<br />

extracts, this compound was found to induce hypotension, diuresis, and<br />

natiuresis (40). On the basis of the results obtained, stevioside has actually been<br />

suggested for the clinical treatment of hypertension in humans (40).<br />

Urinary enzyme levels, changes in blood urea nitrogen (BUN) and plasma<br />

creatinine levels, and ultrastructural changes in the kidney have been examined<br />

after a single high dose of 1.5 g/kg body weight of stevioside in rats administered<br />

by subcutaneous injection. The levels of BUN and plasma creatinine both increased,<br />

as did urinary glucose. Histopathological examination showed nephrotoxicity<br />

in the proximal convoluted tubules of the kidney rather than the glomeruli<br />

or other tubules, and it was concluded that the mechanism of toxicity did not<br />

involve lipid peroxidation (41).<br />

A series of studies on the effects of stevioside and several of its glycosidic<br />

and nonglycosidic derivatives on cellular and subcellular metabolism have been<br />

performed and reviewed by Brazilian investigators. The activities of these compounds<br />

have been probed in systems such as rat liver mitochondria, rat renal<br />

cortical tubules, human and rabbit erythrocytes, and rabbit reticulocytes. In general,<br />

S. rebaudiana glycosidic constituents such as stevoside and steviolbioside<br />

are either inactive in these systems or else found to be less active than their<br />

hydrolytic products steviol and isosteviol (2).<br />

VIII. CARIOGENICITY POTENTIAL<br />

Pure stevioside and rebaudioside A were tested for cariogenicity in an albino rat<br />

model. Sixty Sprague-Dawley rats were colonized with Streptococcus sobrinus<br />

and were divided into groups fed basal diet 2000 supplemented with either 0.5%<br />

stevioside, 0.5% rebaudioside A, 30% sucrose, or no compound addition. All<br />

four groups were killed after 5 weeks of feeding, and viable S. sobrinus counts<br />

were enumerated, and caries was evaluated according to Keyes’ technique. It<br />

was concluded that stevioside and rebaudioside were not cariogenic under the<br />

conditions of the study (42). In a recent in vitro study, the eight sweet constituents<br />

of S. rebaudiana (stevioside, rebaudiosides A-E, dulcoside A, steviolbioside) and<br />

two hydrolytic products of stevioside (steviol and isosteviol) were tested against<br />

a panel of cariogenic and periodontopathic oral bacteria. Their antibacterial activity<br />

and their ability to inhibit sucrose-induced adherence, glucan binding, and<br />

glucosyltransferase (GTF) activity were evaluated. None of these compounds<br />

suppressed the growth or acid production of the cariogenic organism, Streptococ-

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