Effects of topical application of lipopolysaccharide and proteases on hepatic injury induced by high-cholesterol diet in rats.
OBJECTIVE
Topical application of lipopolysaccharide and proteases to the gingival sulcus induced not only periodontal inflammation but also detectable liver changes in rats fed a normal diet. However, these changes in the liver were not sufficient to induce pathological consequences. The purpose of the present study was to investigate whether gingival inflammation-induced liver change would have more dramatic pathological consequences in rats fed a high-cholesterol diet compared with the effect of the high-cholesterol diet alone.


METHODS
Twenty-four male Wistar rats were divided into four groups. During an 8 week experimental period, two groups were fed a normal diet and the other two were fed a high-cholesterol diet containing 1% cholesterol (w/w) and 0.5% cholic acid (w/w). Four weeks prior to the end of the experimental period, one of each of the dietary groups received daily topical application of lipopolysaccharide and proteases to the gingival sulcus, while the other was treated with pyrogen-free water.


RESULTS
In the rats without application of lipopolysaccharide and proteases, the serum level of hexanoyl-lysine, scores of steatosis and inflammation, and concentration of 8-hydroxydeoxyguanosine in liver of rats fed a high-cholesterol diet were higher than in those fed a normal diet. In rats fed a high-cholesterol diet, the scores of steatosis and inflammation and the concentration of 8-hydroxydeoxyguanosine in the liver of rats with application of lipopolysaccharide and proteases were higher than in those without.


CONCLUSIONS
In a rat model, application of lipopolysaccharide and proteases to the gingival sulcus augmented the effect of a high-cholesterol diet on steatosis, inflammation and oxidative damage in the liver.
Yamamoto
T
T
Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho, Okayama, Japan. tatsuo@md.okayama-u.ac.jp
Tomofuji
T
T
Tamaki
N
N
Ekuni
D
D
Azuma
T
T
Sanbe
T
T
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000287:Administration, Topical; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000009:adverse effects*; D002097:C-Reactive Protein / Q000032:analysis; D002791:Cholesterol, Dietary / Q000009:adverse effects* / Q000097:blood; D019826:Cholic Acid / Q000009:adverse effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004926:Escherichia coli; D005234:Fatty Liver / Q000209:etiology; D005881:Gingiva / Q000187:drug effects; D006505:Hepatitis / Q000209:etiology; D008054:Lipid Peroxides / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology* / Q000473:pathology; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D008930:Mitochondria, Liver / Q000648:ultrastructure; D010447:Peptide Hydrolases / Q000008:administration & dosage / Q000009:adverse effects*; D010518:Periodontitis / Q000209:etiology* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000097:blood; D013305:Streptomyces griseus / Q000201:enzymology
D001426:Bacterial Proteins; D002791:Cholesterol, Dietary; D008054:Lipid Peroxides; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002097:C-Reactive Protein; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010447:Peptide Hydrolases; D019826:Cholic Acid; D003849:Deoxyguanosine; D008239:Lysine