Multiple Periapical Lesions Influence the Expression of TLR4/NF‐κB Pathway Components and the Development of Hepatic Injuries in Healthy and Chronic Alcohol‐Consuming Rats

Aim 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. Methodology 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). Results 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. Conclusions 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.