Biochemical and Toxicological Evaluation of Atorvastatin and Riboflavin in Diethylnitrosamine Induced Hepatocellular Carcinoma

Background: Atorvastatin, a commonly prescribed drug for the management of hyperlipidemia, acts as competitive inhibitors of HMG-CoA reductase—a rate-limiting enzyme in cholesterol synthesis. On the other hand, riboflavin is also a well-studied micronutrient known for its anti-proliferative, anti-metastatic and antioxidant properties. However, the synergistic or antagonistic effect of both drugs when administered together is not studied yet.

Method: This study was an attempt to evaluate the toxicity/efficacy of atorvastatin (30 mg/kg) in combination with riboflavin in hepatocarcinogenic rats when challenged by a single diethylnitrosamine DENA (160 mg/kg; I.P). Serum ALT, AST, creatine kinase, urea, uric acid, creatinine, bilirubin, albumin, LDL, FT3, FT4, calcium, phosphorus, and triglyceride levels were estimated. Histopathology was also performed to study the alterations in the cellular architecture of cardiac and hepatic cells.

Results: Result revealed that DENA significantly plummeted (P < 0.001) most of the parameters when compared with normal control. Atorvastatin+Riboflavin group significantly managed to restore the altered parameters like LDH, cholesterol, triglycerides and LDL-C. Nonetheless, this drug combination also caused mild hepatic damage by increasing the ALT, AST, total bilirubin and creatine kinase. The histopathology revealed that liver sample of DENA+ATS+B2 group exhibited severe necrosis with substantial fat depositions and binucleated cells, whereas the heart sample revealed partial detachment of cells with increased intracellular gaps.

Conclusion: It is suggested from current results that this combination therapy was not only unsupportive to hepatocellular carcinoma treatment but damaging to the hepatic and cardiac cells.