Multiple Periapical Lesions Influence the Expression of TLR4/NF-κB Pathway Components and the Development of Hepatic...

To evaluate the impact of multiple apical periodontitis (AP) on the expression of TLR4/NF-κB pathway components, proinflammatory cytokine levels, and development of hepatic injuries in rats with and without chronic alcohol consumption.

Thirty-two rats were assigned to four groups (n = 8): Control, AP, Alcohol, and Alcohol+AP. The Alcohol and Alcohol+AP groups received 25% ethanol solution. Multiple AP were induced through pulp exposure of four molars for 28 days. Following euthanasia, the jaws and livers were collected. Micro-computed tomography was used to confirm periapical lesions. Liver samples underwent histopathological analysis and ELISA assay to measure TLR4, NF-κB, IL-6, and TNF-α levels. Histopathological evaluation was performed using hepatic stereology to assess hepatocytes, sinusoids, Kupffer cells, steatosis, leukocyte infiltrate, and necrosis. Statistical analysis was carried out using one-way ANOVA followed by the Student-Newman-Keuls (p < 0.05).

Hepatic levels of TLR4 and NF-κB were significantly higher in AP and Alcohol+AP groups compared to Control and Alcohol groups (p < 0.05). IL-6 and TNF-α were significantly elevated in all experimental groups compared to the Control group (p < 0.05), with higher levels observed in the Alcohol+AP group compared to the other groups (p < 0.05). Experimental groups showed a significant reduction in hepatocyte density compared to the Control group (p < 0.05), while sinusoidal volume was significantly reduced in the AP group compared to the Control group (p < 0.05). Hepatic steatosis was absent in the Control and AP groups and there was no significant difference in the percentage of steatosis between Alcohol and Alcohol+AP groups (p > 0.05). No significant differences were observed in the number of Kupffer cells among groups (p > 0.05) and leukocyte infiltrate was absent in all groups. Necrosis was significantly higher in the AP and Alcohol+AP groups compared to the Control and Alcohol groups (p < 0.05), with the Alcohol+AP group showing a higher percentage of necrosis compared to the AP group (p < 0.05). Hydropic degeneration, focal inflammatory infiltrates, and hepatocyte necrosis were observed in the AP and Alcohol+AP groups.

Multiple AP led to elevated TLR4, NF-κB, IL-6, and TNF-α levels and significant hepatic alterations including hepatocyte degeneration and necrosis. When combined with alcohol consumption, multiple AP exacerbated ethanol-induced liver damage.