Potential Anti-carcinogenic Effect of Acetazolamide, a Carbonic Anhydrase Enzyme Inhibitor, in Diethylnitrosamine - Induced Hepatocarcinogenesis in Rats

Abstract

number of cancer-related deaths worldwide. Tumoral microenvironment acidity plays a pivotal role in tumoral cell survival, tumoral progression and metastasis. CA-IX and XII are two of several mechanisms by which tumor maintain optimal intracellular pH at the expense of the extracellular environment that turns into acidic pH. ACT is a CA inhibitor that is used in many medical indications. It is effective, safe and inexpensive. It has some side effects and it may be even contraindicated in some cases. Aim of the Work: To evaluate the possible anticarcinogenic role of ACT in DEN-induced HCC animal model. Materials and Methods: This study showed that using DEN for 10 weeks caused significant increase in the levels of AST, ALT, total bilirubin, direct bilirubin and AFP and significant decrease in albumin level in DEN-induced HCC rat groups when compared to normal control rats. Administration of ACT for 3 weeks in ACT-treated DEN-induced HCC group caused marked improvement in the mentioned biochemical measurements (AST, ALT, total bilirubin, direct bilirubin and AFP) when compared to DEN-induced HCC rat group without ACT treatment, yet still higher than the lab values of normal control group. Results: The present study demonstrated that using DEN in rat groups had induced polyhedral to round hepatocytes with dense, centrally located vesicular nuclei. The neoplastic areas showed poorly differentiated large cells with hyperchromatic nuclei and prominent nucleoli. The neoplastic cells showed anisokaryosis, anisocytosis, and deeply basophilic scanty cytoplasm and frequent mitotic figures mostly Grade III. The hepatic lobule displayed disorganization of hepatic cords with hyperplasia of Kupffer cells, multinucleated tumor giant cells with prominent basophilic nuclei and basophilic spindle cells. Conclusion: Acetazolamide showed significant antitumor effect in DEN-induced HCC in rats, making it a promising agent to use against HCC either individually or in combination with any other therapeutic modalities. Further researches should be conducted in this anti HCC aspect.