Efficacy of structurally diverse aldose reductase inhibitors on experimental periodontitis in rats

Peter F Kador, James D. O'Meara, Karen Blessing, David B. Marx, Richard A Reinhardt

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: To study aldose reductase and the sorbitol pathway in periodontitis and diabetes, rats with experimental periodontitis with or without diabetes were treated with three structurally diverse aldose reductase inhibitors (ARIs). Methods: Periodontitis was induced with three consecutive palatal injections of Porphyromonas gingivalis lipopolysaccharide (LPS) at 48-hour intervals between the first and second molars on the right side in young, age-matched, streptozotocin-induced rats with and without diabetes 44 days after initiation of diets with and without the ARIs tolrestat, imirestat, and quercetin. As an internal control, phosphate-buffered saline (PBS) was similarly injected on the left side. Twenty-four days after the final injection, all rats were euthanized. Defleshed samples were stained with 5% toluidine blue and palatal digital images were traced to include the enamel crown and exposed root. The root/enamel ratios (to estimate alveolar bone loss) were analyzed with repeated measures analysis of variance. Results: LPS injections resulted in significantly more bone loss versus PBS injections in both the rats with and without diabetes on normal diets (P <0.0001). All three ARIs significantly reduced LPS-induced periodontitis in the animals with and without diabetes (P ≤0.003) to the level where they were not different from PBS-injected sites in normal diet controls. Conclusion: All ARIs demonstrated efficacy in preventing alveolar bone loss because of periodontitis in both animals with and without diabetes, suggesting a role for the sorbitol pathway and the potential for ARIs to reduce inflammatory responses downstream from aldose reductase.

Original languageEnglish (US)
Pages (from-to)926-933
Number of pages8
JournalJournal of periodontology
Volume82
Issue number6
DOIs
StatePublished - Jun 1 2011

Fingerprint

Aldehyde Reductase
Periodontitis
Alveolar Bone Loss
Lipopolysaccharides
Injections
Sorbitol
Phosphates
Dental Enamel
Diet
Tolonium Chloride
Porphyromonas gingivalis
Quercetin
Streptozocin
Crowns
Analysis of Variance
Bone and Bones

Keywords

  • Diabetes mellitus
  • Enzyme inhibitors
  • Models, animal
  • Periodontitis

ASJC Scopus subject areas

  • Periodontics

Cite this

Efficacy of structurally diverse aldose reductase inhibitors on experimental periodontitis in rats. / Kador, Peter F; O'Meara, James D.; Blessing, Karen; Marx, David B.; Reinhardt, Richard A.

In: Journal of periodontology, Vol. 82, No. 6, 01.06.2011, p. 926-933.

Research output: Contribution to journalArticle

@article{d09d6db85b79443ba75f688839f5016e,
title = "Efficacy of structurally diverse aldose reductase inhibitors on experimental periodontitis in rats",
abstract = "Background: To study aldose reductase and the sorbitol pathway in periodontitis and diabetes, rats with experimental periodontitis with or without diabetes were treated with three structurally diverse aldose reductase inhibitors (ARIs). Methods: Periodontitis was induced with three consecutive palatal injections of Porphyromonas gingivalis lipopolysaccharide (LPS) at 48-hour intervals between the first and second molars on the right side in young, age-matched, streptozotocin-induced rats with and without diabetes 44 days after initiation of diets with and without the ARIs tolrestat, imirestat, and quercetin. As an internal control, phosphate-buffered saline (PBS) was similarly injected on the left side. Twenty-four days after the final injection, all rats were euthanized. Defleshed samples were stained with 5{\%} toluidine blue and palatal digital images were traced to include the enamel crown and exposed root. The root/enamel ratios (to estimate alveolar bone loss) were analyzed with repeated measures analysis of variance. Results: LPS injections resulted in significantly more bone loss versus PBS injections in both the rats with and without diabetes on normal diets (P <0.0001). All three ARIs significantly reduced LPS-induced periodontitis in the animals with and without diabetes (P ≤0.003) to the level where they were not different from PBS-injected sites in normal diet controls. Conclusion: All ARIs demonstrated efficacy in preventing alveolar bone loss because of periodontitis in both animals with and without diabetes, suggesting a role for the sorbitol pathway and the potential for ARIs to reduce inflammatory responses downstream from aldose reductase.",
keywords = "Diabetes mellitus, Enzyme inhibitors, Models, animal, Periodontitis",
author = "Kador, {Peter F} and O'Meara, {James D.} and Karen Blessing and Marx, {David B.} and Reinhardt, {Richard A}",
year = "2011",
month = "6",
day = "1",
doi = "10.1902/jop.2010.100442",
language = "English (US)",
volume = "82",
pages = "926--933",
journal = "Journal of Periodontology",
issn = "0022-3492",
publisher = "American Academy of Periodontology",
number = "6",

}

TY - JOUR

T1 - Efficacy of structurally diverse aldose reductase inhibitors on experimental periodontitis in rats

AU - Kador, Peter F

AU - O'Meara, James D.

AU - Blessing, Karen

AU - Marx, David B.

AU - Reinhardt, Richard A

PY - 2011/6/1

Y1 - 2011/6/1

N2 - Background: To study aldose reductase and the sorbitol pathway in periodontitis and diabetes, rats with experimental periodontitis with or without diabetes were treated with three structurally diverse aldose reductase inhibitors (ARIs). Methods: Periodontitis was induced with three consecutive palatal injections of Porphyromonas gingivalis lipopolysaccharide (LPS) at 48-hour intervals between the first and second molars on the right side in young, age-matched, streptozotocin-induced rats with and without diabetes 44 days after initiation of diets with and without the ARIs tolrestat, imirestat, and quercetin. As an internal control, phosphate-buffered saline (PBS) was similarly injected on the left side. Twenty-four days after the final injection, all rats were euthanized. Defleshed samples were stained with 5% toluidine blue and palatal digital images were traced to include the enamel crown and exposed root. The root/enamel ratios (to estimate alveolar bone loss) were analyzed with repeated measures analysis of variance. Results: LPS injections resulted in significantly more bone loss versus PBS injections in both the rats with and without diabetes on normal diets (P <0.0001). All three ARIs significantly reduced LPS-induced periodontitis in the animals with and without diabetes (P ≤0.003) to the level where they were not different from PBS-injected sites in normal diet controls. Conclusion: All ARIs demonstrated efficacy in preventing alveolar bone loss because of periodontitis in both animals with and without diabetes, suggesting a role for the sorbitol pathway and the potential for ARIs to reduce inflammatory responses downstream from aldose reductase.

AB - Background: To study aldose reductase and the sorbitol pathway in periodontitis and diabetes, rats with experimental periodontitis with or without diabetes were treated with three structurally diverse aldose reductase inhibitors (ARIs). Methods: Periodontitis was induced with three consecutive palatal injections of Porphyromonas gingivalis lipopolysaccharide (LPS) at 48-hour intervals between the first and second molars on the right side in young, age-matched, streptozotocin-induced rats with and without diabetes 44 days after initiation of diets with and without the ARIs tolrestat, imirestat, and quercetin. As an internal control, phosphate-buffered saline (PBS) was similarly injected on the left side. Twenty-four days after the final injection, all rats were euthanized. Defleshed samples were stained with 5% toluidine blue and palatal digital images were traced to include the enamel crown and exposed root. The root/enamel ratios (to estimate alveolar bone loss) were analyzed with repeated measures analysis of variance. Results: LPS injections resulted in significantly more bone loss versus PBS injections in both the rats with and without diabetes on normal diets (P <0.0001). All three ARIs significantly reduced LPS-induced periodontitis in the animals with and without diabetes (P ≤0.003) to the level where they were not different from PBS-injected sites in normal diet controls. Conclusion: All ARIs demonstrated efficacy in preventing alveolar bone loss because of periodontitis in both animals with and without diabetes, suggesting a role for the sorbitol pathway and the potential for ARIs to reduce inflammatory responses downstream from aldose reductase.

KW - Diabetes mellitus

KW - Enzyme inhibitors

KW - Models, animal

KW - Periodontitis

UR - http://www.scopus.com/inward/record.url?scp=79958234707&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958234707&partnerID=8YFLogxK

U2 - 10.1902/jop.2010.100442

DO - 10.1902/jop.2010.100442

M3 - Article

VL - 82

SP - 926

EP - 933

JO - Journal of Periodontology

JF - Journal of Periodontology

SN - 0022-3492

IS - 6

ER -