Novel protective role of curcumin and taurine combination against experimental hepatocarcinogenesis

Abstract

Hepatocarcinogenesis is a prerequisite to hepatocellular carcinoma (HCC), which is one of the most common cancers among humans. Therefore, it is important to search for agents that protect against hepatocarcinogenesis. The present study aimed to investigate the protective effects of a combination of taurine and curcumin against experimental hepatocarcinogenesis induced by diethyl nitrosamine (DENA) in a rat model. A total of 100 rats were divided into eight groups. Eight weeks following DENA injection and treatment with curcumin and taurine, the rats were sacrificed to obtain blood and hepatic tissue samples for the evaluation of various markers and histopathological observations. Serum levels of interleukin-2 (IL-2), interferon-γ (IFN-γ), α-fetoprotein (AFP) and α-L-fucosidase (AFU) were determined. Rats injected with DENA for eight weeks showed a high percentage of malignant changes in hepatic tissues, as well as a significant increases in the serum levels of AFP and AFU and significant reductions in the serum levels of IL-2 and IFN-γ. Treatment with curcumin and taurine markedly reduced the extent of malignant changes in the rat liver tissues, with their liver tissues showing patterns similar to that of the normal control rats. In addition, this combination resulted in normal serum levels of IL-2, IFN-γ, AFP and AFU. The results of the present study suggested that a combination of curcumin and taurine may be a novel prophylactic agent against hepatocarcinogenesis in high-risk groups exposed to chemical hepatocarcinogens.

Keywords: curcumin; interferon-γ; interleukin-2; rat hepatocarcinogenesis; taurine; α-L-fucosidase; α-fetoprotein.

Figure 1.

Levels of interleukin-2 in the serum of the control, DENA-injected and taurine- and/or curcumin-treated rats. DENA, diethylnitroseamine. *P>0.05; **P<0.05; ***P<0.001.

Figure 2.

Levels of interferon-γ in the serum of the control, DENA-injected and taurine- and/or curcumin-treated rats. DENA, diethylnitroseamine. *P>0.05; **P<0.05; ***P<0.001.

Figure 3.

Photomicrograph of a liver section from untreated control rats showing normal organized hepatic tissue with normal hepatocytes (hematoxylin and eosin staining; magnification, ×400).

Figure 4.

Photomicrograph of a liver section from rats injected with diethylnitroseamine (DENA) for 8 weeks. DENA-injected rats showed malignant hepatocytes arranged in acini, with abundant cytoplasmic vacuolization, as indicative of grade 1 hepatocellular carcinoma (hematoxylin and eosin staining; magnification, ×120).

Figure 5.

Photomicrograph of a liver section from rats pretreated with curcumin and taurine, followed by DENA injection twice a week for 8 weeks. Curcumin- and taurine-treated rats showed reactive hepatocytes, with condensed chromatin and small nuclei. Moderate amount of bile duct proliferation was observed. No malignant lesions were observed (hematoxylin and eosin staining; magnification, ×120).

Figure 6.

Electron micrograph of hepatocytes from control untreated rats showing the nucleus (N) and cytoplasmic organelles, in particular irregular mitochondria (M). The desmosomal junction along the contact line between cell membranes (arrow). (L) Lipid droplets. Uranyl acetate and lead citrate staining; magnification, ×4,000.

Figure 7.

Electron micrograph of hepatocytes from diethylnitroseamine-injected rats showing degenerative cytoplasmic vacuolization, disrupted organelles and nuclear malignant changes. (N) Nucleus and (L) lipid droplet. Uranyl acetate and lead citrate staining; magnification, ×4,000.

Figure 8.

Electron micrograph of hepatocytes from curcumin- plus taurine-treated and diethylnitroseamine-injected rats showing the perinuclear zone of the liver containing reactive hepatocytes with condensed chromatin and small nucleoli (N). Preservation of the hepatocytes and reorganization of venous congestion in the central veins was observed. There was an increased number of lipid droplets (L), and pools of glycogen (arrow) were noticed in the absence of malignant changes (uranyl acetate and lead citrate staining, magnification, ×4,000).