Allopurinol abates hepatocellular carcinoma in rats via modulation of NLRP3 inflammasome and NF-κB pathway

The present research was performed to examine the possible capability of allopurinol to prevent developing hepatocellular carcinoma (HCC) and to explore the fundamental mechanisms that control the hepatoprotective effect considering the enormous impact of HCC on patients' quality of life. Male Sprague Dawely rats were given i.p. injection of thioacetamide (TAA) (200 mg/kg) twice a week for 16 weeks in order to induce HCC. The histological analysis and assessment of the serum levels of liver function indicators verified the development of HCC. Two regimens of allopurinol (100 mg/kg, p.o.) were used; the first involved giving it concurrently with TAA from week 13 to week 16, and the second regimen started from week 9 to week 16. Chronic TAA damage was associated with considerable overexpression of the profibrogenic cytokine TGF-beta, degradation and nuclear translocation of NF-kappa B, which released a number of inflammatory mediators, and upregulation of the NLRP3/caspase1 pathway. Administration of allopurinol demonstrated considerable enhancements in liver function and oxidative balance. Moreover, pathological characteristics like cirrhosis, dysplastic changes, and HCC nodules were greatly diminished. Allopurinol via suppressing TGF-beta expression, inhibiting NF-kappa B nuclear translocation, and restricting inflammatory NLRP3/caspase1/IL-1 beta pathway was able to protect against TAA-induced liver damage, and it could be a promising therapy for HCC.