Interactions of Stevioside and Steviol with Renal Organic Anion Transporters in S2 Cells and Mouse Renal Cortical Slices

Srimaroeng, Chutima; Jutabha, Promsuk; Pritchard, John B.; Endou, Hitoshi; Chatsudthipong, Varanuj

doi:10.1007/s11095-005-4580-5

Cited by 20 publications

(10 citation statements)

References 38 publications

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“…The PAH transport, or organic anion transporter 1 (OAT1), is one of at least three basolateral membrane organic anion transport systems (named OAT2 and OAT3, other than apical membrane OAT4) in rat proximal tubule cells. In rabbit (McKinney, 1982) and mouse (Srimaroeng et al, 2005) it appeared localized in the S 2 segment, in contrast to Tune et al (1969) who reported active secretion in both segments, the secretion rate being 3 times higher in the S 3 segment. In rats, results are conflicting: Roch-Ramel and Weiner (1980) and Roch-Ramel et al (1980) localized PAH transport in the S 2 and S 3 segments; Hook et al (1982), by means of a segment-specific nephrotoxicants as HCBD suggested localization in S 3 segment.…”

Section: Discussioncontrasting

confidence: 63%

Renal Proximal Tubule Segment-Specific Nephrotoxicity: An Overview on Biomarkers and Histopathology

Cristofori

Zanetti²,

Fregona

et al. 2007

Toxicol Pathol

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The correspondence between histopathological findings and segment-specific biomarkers was investigated in rats treated with segment-specific nephrotoxicants. Male Wistar rats were treated with a single injection of K 2 Cr 2 O 7 (25 mg/kg sc in saline), cis-Pt (10 mg/kg ip in buffered MSO) or HCBD (100 mg/kg ip in corn oil). Twenty-four and 48 hours after treatment, the rats were sacrificed and the kidneys were drawn for histopathological and biochemical evaluation, i.e., GS activity in renal cortex and PAH uptake in renal cortical slices. Histopathological findings show that cis-Pt and HCBD cause diffuse necrosis of S 3 segment of proximal tubules in the outer stripe of outer medulla, respectively. On the contrary, K 2 Cr 2 O 7 damages exclusively S 1 -S 2 segments, inducing vacuolization at 24 hr and diffuse necrosis at 48 hr after treatment. GS activity in renal tissue is significantly decreased after HCBD and cis-Pt, but not K 2 Cr 2 O 7 treatment. In contrast, PAH uptake is significantly reduced by K 2 Cr 2 O 7 , but not by cis-Pt or HCBD treatment (even if HCBD causes a slight decrease 48 hr after treatment). The evidence of this study confirms the high specificity of GS activity as marker of S 3 segment injury, that PAH uptake is prevalently active in the S 1 -S 2 segments, and that there is complete correspondence among segment-specific nephrotoxicants, biomarkers of segment-specific damage, and histopathological findings.

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Section: Discussioncontrasting

confidence: 63%

Renal Proximal Tubule Segment-Specific Nephrotoxicity: An Overview on Biomarkers and Histopathology

Cristofori

Zanetti²,

Fregona

et al. 2007

Toxicol Pathol

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“…We previously reported that renal proximal tubule cells that were stably transfected with hOAT1 and hOAT3 were less viable after their exposure to steviol for 3 days at concentrations ranging between 25 and 100 M (Srimaroeng et al, 2005). However, up to 200 M dihydroisosteviol did not affect T84 cell viability.…”

Section: Discussionmentioning

confidence: 94%

“…The effects of stevioside and steviol on membrane transporters also have been examined. Stevioside and steviol have been shown to inhibit renal para-aminohippurate transport by rabbit and human organic anion transporters (Chatsudthipong and Jutabha, 2001;Srimaroeng et al, 2005). It is interesting to note that an extract of the Stevia leaf has been shown to have activity against the rotavirus that induces secretory diarrhea (Takahashi et al, 2001).…”

mentioning

confidence: 99%

A Natural Plant-Derived Dihydroisosteviol Prevents Cholera Toxin-Induced Intestinal Fluid Secretion

Pariwat

Homvisasevongsa²,

Muanprasat³

et al. 2007

J Pharmacol Exp Ther

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Stevioside and its major metabolite, steviol, have been reported to affect ion transport in many types of tissues, such as the kidney, pancreas, and intestine. The effect of stevioside, steviol, and its analogs on intestinal Cl Ϫ secretion was investigated in a human T84 epithelial cell line. Short-circuit current measurements showed that steviol and analogs isosteviol, dihydroisosteviol, and isosteviol 16-oxime inhibited in a dosedependent manner forskolin-induced Cl Ϫ secretion with IC 50 values of 101, 100, 9.6, and 50 M, respectively, whereas the parent compound stevioside had no effect. Apical Cl Ϫ current measurement indicated that dihydroisosteviol targeted the cystic fibrosis transmembrane regulator (CFTR). The inhibitory action of dihydroisosteviol was reversible and was not associated with changes in the intracellular cAMP level. In addition, dihydroisosteviol did not affect calcium-activated chloride secretion and T84 cell viability. In vivo studies using a mouse closed-loop model of cholera toxin-induced intestinal fluid secretion showed that intraluminal injection of 50 M dihydroisosteviol reduced intestinal fluid secretion by 88.2% without altering fluid absorption. These results indicate that dihydroisosteviol and similar compounds could be a new class of CFTR inhibitors that may be useful for further development as antidiarrheal agents.

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“…It is not yet known if or under what conditions this is clinically relevant in the case of saccharin. OATs have also been implicated in the excretion of steviol (Srimaroeng et al 2005), the metabolite of steviol glycosides (stevioside and rebaudioside), but the clinical significance is not known. Interestingly, steviol is sold commercially as an OAT inhibitor (Sigma-Aldrich 2012).…”

Section: Research Need 3: Determine If High-potency Sweeteners Alter mentioning

confidence: 99%

Rationale for Further Medical and Health Research on High-Potency Sweeteners

Schiffman

2012

Chemical Senses

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High-potency or artificial sweeteners have historically been considered inert compounds without physiological consequences other than taste sensations. However, recent data suggest that some of these sweeteners have biological effects that may impact human health. Furthermore, there are significant gaps in our current knowledge of the pharmacokinetics of these sweeteners, their potential for “sweetener–drug interactions” and their impact on appetite and body weight regulation. Nine research needs are described that address some of the major unknown issues associated with ingestion of high-potency sweeteners.

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Interactions of Stevioside and Steviol with Renal Organic Anion Transporters in S2 Cells and Mouse Renal Cortical Slices

Abstract: Stevioside has no interaction with human or mouse OATs. In contrast, steviol interacts directly with human OATs, in particular, hOAT1 and hOAT3, with a potency approximating probenecid, suggesting that the inhibition of OAT-mediated transport by steviol could alter renal drug clearance.

Cited by 20 publications

References 38 publications

Renal Proximal Tubule Segment-Specific Nephrotoxicity: An Overview on Biomarkers and Histopathology

Renal Proximal Tubule Segment-Specific Nephrotoxicity: An Overview on Biomarkers and Histopathology

A Natural Plant-Derived Dihydroisosteviol Prevents Cholera Toxin-Induced Intestinal Fluid Secretion

Rationale for Further Medical and Health Research on High-Potency Sweeteners

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