Histological effects and pharmacokinetics of lipopolysaccharide derived from Porphyromonas gingivalis on rat maxilla and liver concerning with progression into non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is one of the chronic liver diseases that can develop into hepatocirrhosis. The purpose of the present study was to investigate the impact of lipopolysaccharide (LPS) from Porphyromonas gingivalis (P. gingivalis) on NASH onset, and to determine the biodistribution of double-radiolabeled LPS (R-LPS) biosynthesized in P. gingivalis.Rats fed a basal diet (BD) or a high-fat diet (HD) were injected with P. gingivalis-LPS or R-LPS into the palatine gingiva around the right maxillary first molar, and were classified into the following 4 groups: BD/LPS (-), BD/LPS (+), HD/LPS (-), and HD/LPS (+) or 2 groups: BD/R-LPS and HD/R-LPS.Inflammation in the gingiva of the LPS (+) groups progressed significantly more than the LPS (-) groups. Furthermore, in the HD/LPS (+) liver, histologic analysis confirmed the presence of NASH, characterized by large fat droplets, ballooning degeneration, and infiltration of inflammatory cells. When 3 H, 14 C-R-LPS was injected into the palatine gingiva, radioactivity in the right palatal mucosa of HD/R-LPS rats was the highest in comparison with other regions and was significantly elevated after 24 hours compared to BD/R-LPS rats. Autoradiographic analysis of the maxilla showed distributions from the palatal mucosa to the hard palate and the interdental region. Radioactivity in organs of both BD/R-LPS and HD/R-LPS rats were mostly localized to the liver even after 24 hours.The present study suggests that the transfer of P. gingivalis-LPS from the oral cavity to the liver plays an important role in disease exacerbation of NASH.