Protective and therapeutic effects of sildenafil and tadalafil on aflatoxin B1-induced hepatocellular carcinoma
Abstract
Hepatocellular carcinoma (HCC) has been classified as one of the most common forms of liver cancer occurring worldwide, and risk factors include hepatitis B & C virus, alcoholism, and dietary carcinogens like aflatoxin B1 (AFB1), which is produced by fungus Aspergillus flavus and Aspergillus parasiticus. Metabolism of AFB1 resulted into the formation of AFB1-exo-8, 9-epoxide which is largely responsible for HCC development. So far conventional cytotoxic chemotherapy has not provided much benefit in HCC, necessitating the need for newer treatment modalities. Recent reports suggest that phosphodiesterase-5 inhibitors (PDE5i) may have anticancer activity, but till date, the anticancer property of PDE5i (tadalafil & sildenafil) has not been evaluated in HCC. The present study was aimed to define the anticancer property of tadalafil and sildenafil against AFB1-induced HCC rats. Rats were randomly divided into five groups with five rats in each group. Except normal control group, rats of all other groups were fed with 5% alcohol via drinking water for 3 weeks. After 3 weeks, two successive dose of AFB1 (1 mg/kg bw, ip) was administered on subsequent days followed by the administration of PDE5i (tadalafil & sildenafil, 10 mg/kg bw) along with drinking water after 6 weeks of treatment with AFB1 for 2 weeks. An in-depth investigation into its mechanistic aspect revealed that development of HCC induced by aflatoxin B1, decreased the mRNA expression and activity of antioxidant enzyme…
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