Effects of rosuvastatin on inducible nitric oxide synthase in rats with hyperlipidaemia and periodontitis

J Periodontal Res. 2018 Apr;53(2):258-266. doi: 10.1111/jre.12513. Epub 2017 Oct 31.

Abstract

Background and objective: Nitric oxide is a free radical that is synthesized from l-arginine by nitric oxide synthase (NOS). The level of inducible NOS (iNOS) in gingiva with periodontitis is higher than that in healthy gingiva. The aim of this study was to evaluate the effects of rosuvastatin administration on alveolar bone loss (ABL) and iNOS(+) cell counts in gingival tissues in rats with ligature-induced experimental periodontitis with/without hyperlipidaemia.

Material and methods: The rats were randomly divided into seven groups: Hy (cholesterol-added diet/water administration); HyP (cholesterol-added diet/periodontitis/water administration); HyPR (cholesterol-added diet/periodontitis/rosuvastatin administration); P (standard diet/periodontitis/water administration); PR (standard diet/periodontitis/rosuvastatin administration); C (standard diet/water administration); and R (standard diet/rosuvastatin administration). Experimental periodontitis was induced with silk ligatures, and rosuvastatin/water was administered to rats by oral gavage for the last 2 weeks of the 8-week study. After the rats were killed in week 8, histomorphometric and histological analyses were performed. Immunostained iNOS(+) cells were counted in the gingival samples and the Mann-Whitney U-test was used for statistical analysis.

Results: The experimental groups exhibited increases in total cholesterol and low-density lipoprotein, except for Groups C and R. The cholesterol-added diet induced ABL in Group Hy. Of the periodontitis groups, the lowest ABL was found in Group PR. While there was a significant difference in ABL between Groups P (0.82 ± 0.15 mm) and PR (0.70 ± 0.21 mm) receiving a standard diet (P < .05), no difference was observed between Groups HyP (0.77 ± 0.07 mm) and HyPR (0.76 ± 0.11 mm) receiving a cholesterol-added diet (P ˃ .05). Rosuvastatin significantly reduced expression of iNOS in Groups PR (18.40 ± 2.31%) and HyPR (24.00 ± 4.83%) compared with Group P (30.90 ± 2.42%; P < .001). However, a larger number of iNOS(+) cells was found in Group HyPR than in Group PR (P < .001).

Conclusion: Administration of rosuvastatin reduced gingival iNOS expression in ligature-induced periodontitis with/without hyperlipidaemia. It also led to significant differences in ABL in rats with periodontitis, except when periodontitis was associated with hyperlipidaemia. These findings could provide an important contribution in further studies to evaluate the role of rosuvastatin as a host modulatory agent in the pathogenesis of periodontal diseases.

Keywords: cholesterol; gingiva; inducible nitric oxide synthase; periodontitis; rosuvastatin.

MeSH terms

  • Alveolar Bone Loss / drug therapy
  • Animals
  • Body Weight
  • Cell Count
  • Cholesterol / blood
  • Cholesterol, Dietary
  • Disease Models, Animal
  • Gingiva / diagnostic imaging
  • Gingiva / drug effects
  • Gingiva / pathology
  • Hyperlipidemias / complications*
  • Lipoproteins, LDL / blood
  • Male
  • Molar / diagnostic imaging
  • Molar / pathology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / drug effects*
  • Nitric Oxide Synthase Type II / metabolism*
  • Periodontitis / complications*
  • Periodontitis / pathology
  • Rats
  • Rats, Wistar
  • Rosuvastatin Calcium / administration & dosage
  • Rosuvastatin Calcium / pharmacology*

Substances

  • Cholesterol, Dietary
  • Lipoproteins, LDL
  • Nitric Oxide
  • Rosuvastatin Calcium
  • Cholesterol
  • Nitric Oxide Synthase Type II