Evaluation of the effect of metformin on gingivitis caused by experimental Alzheimer's disease in male rats

Authors

  • Mohammad Sofiabadi
  • Ensiyeh Bahadoran
  • Jalaloddin Hamisi
  • Fatemeh Samieerad
  • Mohammad Hossein Esmaeili
  • Narges Kazemi Alamouti
  • Omid Amirbandeh

DOI:

https://doi.org/10.31989/bchd.v8i10.1687

Abstract

Background: Periodontitis is associated with several comorbidities, including Alzheimer's disease (AD). Metformin (MET) has been shown to affect AD positively.

Objectives: In the present study, the effectiveness of MET in gingivitis caused by experimental AD was investigated in male rats. 

Methods: Forty male Wistar rats were randomly divided into five experimental groups (n=8 per group) as follows: control, intracerebroventricular (ICV) injection of 10 μL of citrate buffer (solvent); streptozotocin (STZ), ICV injection of (3 mg/kg) STZ; and three groups of STZ + MET, ICV injection of STZ and different dosages of MET (50, 100, 200 mg/kg i. p.). 24 hours after the last injection, the Morris water maze test was administered to each animal. The mice were then sacrificed under deep anesthesia, and sampling of the papilla around the two central incisor teeth was performed. The number of inflammatory cells, angiogenesis, fibroblasts, and collagen deposition were evaluated. The results were analyzed using ANOVA and Tukey's test.

Results: The results showed that the STZ injection significantly impaired learning and spatial memory. Moreover, STZ significantly increased periodontal inflammatory cells, angiogenesis, fibroblasts, and collagen deposition in the gingiva of rats compared with the control group. Additionally, MET improved learning and spatial memory and reduced histopathologic parameters in the gingiva of experimental Alzheimer's model rats.

Novelty of Study: This study fills a significant gap in evaluating the effect of MET on gingival inflammation linked to Alzheimer’s disease (GAD) using a STZ-induced rat model. While previous research has explored metformin’s neuroprotective and anti-inflammatory roles separately, this study uniquely combines behavioral assessments and histological analysis to show that metformin improves cognitive performance and reduces gingival inflammation. This study is the first to demonstrate that MET reduces gingival inflammation associated with experimental AD while simultaneously improving cognitive function, suggesting a dual therapeutic role.

Conclusions: Based on these findings, AD may cause or aggravate gingivitis. Moreover, MET has the potential to alleviate AD symptoms and experimental gingivitis caused by AD in rats.

Keywords: Alzheimer's disease, metformin, inflammatory cells, periodontal diseases, rats, gingival inflammation, dual-action effect, novel therapy

Published

2025-10-24

Issue

Section

Research Articles