Krebswissenschaft und -therapie

Silibinin Inhibits the Hepatocellular Carcinoma in NDEA-Induced Rodent Carcinogenesis Model: An Evaluation through Biochemical and Bio-Structural Parameters

Abstract

Abhishek Kumar, Priyashree Sunita and Shakti P Pattanayak

The present study was aimed to investigate the chemopreventive potential of Silibinin (SIB) against N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma (HCC) in wistar rats. Thirty experimental animals were subjected to partial hepatectomy (PH) and after 24 hours of stabilization period a single dose of NDEA (100 mg/kg b.w., i.p) was administered to each animal followed by CCl4 (1 ml/kg b.w., s.c.). The effect of SIB (25 and 50 mg/kg/day, i.p.) on NDEA-induced HCC was determined after 2 weeks of treatment (6th to 8th week after PH, in the promotional stage of tumor development). NDEA treatment to rats resulted in significant decrease in body weight and increase in liver weight along with levels of transaminases, γ-glutamyl transferase, lipoprotein, glycoproteins. Hepatic and serum malondialdehyde content, enzymatic and non-enzymatic antioxidant levels were also altered in HCC bearing animals without treatment. Bio-structural components (such as amide bands of proteins, symmetric phosphate stretching of nucleic acids, methylene chains in membrane lipids, methyl to methylene ratio of carbohydrates and proteins etc.) were marked in NDEA-treated groups of animals by analysing changes in the position and intensities of the peaks in Fourier transform infrared spectroscopy (FTIR). Immunohistochemical staining of Ki67 and histopathological analysis were also carried out in order to support the study. SIB treatment could attenuate NDEA-induced hepatocarcinogenesis by improving the biochemical and bio-structural changes of the hepatic tissue near normal levels in a dose dependent manner. Taken together, this study reveals that SIB may have potential as a multi-functional drug candidate for cancer therapy.