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Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats.
J Toxicol Environ Health A. 2008; 71(21):1415-29.JT

Abstract

Splenda is comprised of the high-potency artificial sweetener sucralose (1.1%) and the fillers maltodextrin and glucose. Splenda was administered by oral gavage at 100, 300, 500, or 1000 mg/kg to male Sprague-Dawley rats for 12-wk, during which fecal samples were collected weekly for bacterial analysis and measurement of fecal pH. After 12-wk, half of the animals from each treatment group were sacrificed to determine the intestinal expression of the membrane efflux transporter P-glycoprotein (P-gp) and the cytochrome P-450 (CYP) metabolism system by Western blot. The remaining animals were allowed to recover for an additional 12-wk, and further assessments of fecal microflora, fecal pH, and expression of P-gp and CYP were determined. At the end of the 12-wk treatment period, the numbers of total anaerobes, bifidobacteria, lactobacilli, Bacteroides, clostridia, and total aerobic bacteria were significantly decreased; however, there was no significant treatment effect on enterobacteria. Splenda also increased fecal pH and enhanced the expression of P-gp by 2.43-fold, CYP3A4 by 2.51-fold, and CYP2D1 by 3.49-fold. Following the 12-wk recovery period, only the total anaerobes and bifidobacteria remained significantly depressed, whereas pH values, P-gp, and CYP3A4 and CYP2D1 remained elevated. These changes occurred at Splenda dosages that contained sucralose at 1.1-11 mg/kg (the US FDA Acceptable Daily Intake for sucralose is 5 mg/kg). Evidence indicates that a 12-wk administration of Splenda exerted numerous adverse effects, including (1) reduction in beneficial fecal microflora, (2) increased fecal pH, and (3) enhanced expression levels of P-gp, CYP3A4, and CYP2D1, which are known to limit the bioavailability of orally administered drugs.

Authors+Show Affiliations

Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27708, USA. donia@duke.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18800291

Citation

Abou-Donia, Mohamed B., et al. "Splenda Alters Gut Microflora and Increases Intestinal P-glycoprotein and Cytochrome P-450 in Male Rats." Journal of Toxicology and Environmental Health. Part A, vol. 71, no. 21, 2008, pp. 1415-29.
Abou-Donia MB, El-Masry EM, Abdel-Rahman AA, et al. Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. J Toxicol Environ Health A. 2008;71(21):1415-29.
Abou-Donia, M. B., El-Masry, E. M., Abdel-Rahman, A. A., McLendon, R. E., & Schiffman, S. S. (2008). Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. Journal of Toxicology and Environmental Health. Part A, 71(21), 1415-29. https://doi.org/10.1080/15287390802328630
Abou-Donia MB, et al. Splenda Alters Gut Microflora and Increases Intestinal P-glycoprotein and Cytochrome P-450 in Male Rats. J Toxicol Environ Health A. 2008;71(21):1415-29. PubMed PMID: 18800291.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats. AU - Abou-Donia,Mohamed B, AU - El-Masry,Eman M, AU - Abdel-Rahman,Ali A, AU - McLendon,Roger E, AU - Schiffman,Susan S, PY - 2008/9/19/pubmed PY - 2008/10/3/medline PY - 2008/9/19/entrez SP - 1415 EP - 29 JF - Journal of toxicology and environmental health. Part A JO - J Toxicol Environ Health A VL - 71 IS - 21 N2 - Splenda is comprised of the high-potency artificial sweetener sucralose (1.1%) and the fillers maltodextrin and glucose. Splenda was administered by oral gavage at 100, 300, 500, or 1000 mg/kg to male Sprague-Dawley rats for 12-wk, during which fecal samples were collected weekly for bacterial analysis and measurement of fecal pH. After 12-wk, half of the animals from each treatment group were sacrificed to determine the intestinal expression of the membrane efflux transporter P-glycoprotein (P-gp) and the cytochrome P-450 (CYP) metabolism system by Western blot. The remaining animals were allowed to recover for an additional 12-wk, and further assessments of fecal microflora, fecal pH, and expression of P-gp and CYP were determined. At the end of the 12-wk treatment period, the numbers of total anaerobes, bifidobacteria, lactobacilli, Bacteroides, clostridia, and total aerobic bacteria were significantly decreased; however, there was no significant treatment effect on enterobacteria. Splenda also increased fecal pH and enhanced the expression of P-gp by 2.43-fold, CYP3A4 by 2.51-fold, and CYP2D1 by 3.49-fold. Following the 12-wk recovery period, only the total anaerobes and bifidobacteria remained significantly depressed, whereas pH values, P-gp, and CYP3A4 and CYP2D1 remained elevated. These changes occurred at Splenda dosages that contained sucralose at 1.1-11 mg/kg (the US FDA Acceptable Daily Intake for sucralose is 5 mg/kg). Evidence indicates that a 12-wk administration of Splenda exerted numerous adverse effects, including (1) reduction in beneficial fecal microflora, (2) increased fecal pH, and (3) enhanced expression levels of P-gp, CYP3A4, and CYP2D1, which are known to limit the bioavailability of orally administered drugs. SN - 1528-7394 UR - https://www.unboundmedicine.com/medline/citation/18800291/abstract/Splenda_alters_gut_microflora_and_increases_intestinal_p_glycoprotein_and_cytochrome_p_450_in_male_rats_ L2 - https://www.tandfonline.com/doi/full/10.1080/15287390802328630 DB - PRIME DP - Unbound Medicine ER -