Decrease of Pericytes is Associated With Liver Disease Caused by Ligature-Induced Periodontitis in Rats

• Autores: Daniel Fernando Pereira Vasconcelos, Felipe Rodolfo Pereira da Silva, Moara Silva Conceição Pinto, Lucas de Araújo Bastos Santana, Ingrid Grazielle Souza, Luan Kelves Miranda de Souza, Natássia Cristina Martins Oliveira, Claudio Angelo Ventura, Pedro Duarte Novaes, André Luiz dos Reis Barbosa, Jand Venes Rolim Medeiros, Ivana Mikolasevic, Arya Mani, Jefferson Soares de Oliveira
• Localización: Journal of periodontology, ISSN 0022-3492, Vol. 88, Nº. 2, 2017, págs. 49-57
• Idioma: inglés
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• Resumen

  • Background: Damage caused by periodontitis not only affects periodontal tissues, but also increases the severity of various illnesses such as rheumatoid arthritis, diabetes, and liver diseases. The aim of this study is to investigate the association between induced periodontitis and damage caused through its systemic effects on the liver.

    Methods: Twenty rats were divided into two groups: control and periodontitis. The following parameters were evaluated: gingival bleeding index (GBI), probing depth (PD), myeloperoxidase (MPO) activity, alveolar bone loss (ABL) for periodontal tissues; histopathologic examination of gingival and liver tissues; immunohistochemistry to cells positive for neural/glial antigen 2 (NG2) expressed in hepatic pericytes, glutathione (GSH), and malondialdehyde (MDA) concentrations in liver; and serum levels of alanine aminotransferase and aspartate aminotransferase.

    Results: GBI, PD, MPO, ABL, and histopathologic examinations demonstrated the development of periodontitis. There was a significant increase in microvesicular steatosis accompanied by a marked reduction in NG2+ pericytes in the periodontitis group compared with the control group. The periodontitis group had significantly lower GSH and higher MDA concentration in the liver compared with the control group.

    Conclusions: The present study results link the systemic effects of induced periodontitis with changes in hepatic tissues such as microvesicular steatosis, likely caused by an increase in oxidative stress and lipid peroxidation. The findings from the present study implicate an association between a decrease of pericytes and liver disease caused by ligature-induced periodontitis in rats.

    Periodontitis is an infectious disease of the oral cavity with a prevalence of 4.2% in Oceania to 20.4% in Latin America.1 The disease destroys periodontal supporting and protecting tissues of the teeth.2 This process is complex and involves several components such as a host response influenced by genetics, cells, extracellular matrix, overproduction of free radicals, deregulation of cytokine production, and presence of periodontal pathogens.3-5 Damage caused by periodontitis affects not only periodontal tissues, but also increases the severity of different illnesses such as rheumatoid arthritis,6 diabetes,7 and liver diseases.8,9 Liver disease may be non-alcoholic fatty liver disease (NAFLD), characterized by fatty liver accumulation with a spectrum of liver damage ranging from simple steatosis to non-alcoholic steatohepatitis or severe cases of cancer.10 In Hong Kong, prevalence of NAFLD was 42.9%.11 Exacerbating the situation, 55.7% of NAFLD patients had normal liver enzyme tests.11 Steatosis is associated with metabolic syndrome in the general population and can be considered a multisystem disease associated with inflammation and overproduction of reactive oxygen species, whose byproduct is lipid peroxidation, such as malondialdehyde (MDA) and reduction of antioxidant molecules like glutathione (GSH).12 To evaluate liver disease, histologic analysis is the golden standard, which allows the detection of minimal changes in hepatic structure. Hepatic biology has shown the importance of mast cells that are increased in chronic C virus-related hepatitis.13 In addition, pericytes associated with portal vessels may be niches of cells with a high potential for cell differentiation, as has been demonstrated recently.14 Moreover, regarding liver disease, in previous years, studies8,9 have demonstrated an association with periodontitis. An animal study15 investigating this relationship used Escherichia coli lipopolysaccharide and Streptomyces griseus proteases applied into the gingival sulcus to induce periodontitis and the occurrence of steatosis. Porphyromonas gingivalis, an important periodontal pathogen, presented in the liver of patients with hepatic fibrosis and influenced progression of the liver disease.16 Other studies were conducted associating periodontitis with the progression of viral liver disease,8 with alcohol ingestion or not.17 Corroborating this relationship, recent studies have demonstrated that periodontal therapy may decrease levels of oxidative stress5,18 in the periodontium, saliva, and crevicular fluid and also reduce liver fibrosis.8 Although there are studies showing effects of periodontitis on liver disease,8,9,15-18 there are few studies on oxidative hepatic stress,9,15 and none, to the best knowledge of the authors, investigated lipid peroxidation through MDA levels. Furthermore, and again according to the best knowledge of the authors, there are no studies investigating the influence of mast cells and pericytes on hepatic tissues associated with periodontitis. To elucidate the association, a rat periodontitis model was used in this study.