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Abstract

IN VIVO ANTITUMOR POTENTIAL OF CARVACROL AGAINST HEPATOCELLULAR CARCINOMA IN RAT MODEL

Hanaa H. Ahmed 1* , Wafaa Gh. Shousha 2 , Hatem A. El-Mezayen 2 ,Nora N. Ismaiel 3 , Nadia S. Mahmoud1

1Hormones Department, Medical Research Division, National Research Centre, Dokki, Giza, Egypt.
2Chemistry Department ,Faculty of Science, Helwan University, Cairo , Egypt.
3Molecular Genetics and Enzymology Department, Human Genetics and Genome researches, National Research Centre, Dokki, Giza, Egypt.

ABSTRACT

This study aimed to investigate the efficacy of carvacrol against hepatocellular carcinoma-induced in rats. Forty male rats were divided into 5 groups. Group (1) was negative control. Groups (2), (4) and (5) were orally administrated diethylnitrosamine for induction of hepatocellular carcinoma then group (2) was left untreated ; group (4) was treated orally with carvacrol, while, group (5) were intraperitoneal injected with doxorubicin. Group (3) was orally treated with carvacrol only. Serum alpha-fetoprotein (AFP), alpha L-fucosidase (AFU) and vascular endothelial growth factor (VEGF) levels were assayed using ELISA technique. Gamma glutammyl transferase (GGT) gene expression was detected by RT-PCR. Immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) and Ki-67 expression was performed. Apoptosis was detected using DNA fragmentation assay. Also, histological investigation of liver tissue was achieved. The untreated cancer group showed significant elevation in the studied biochemical markers and appreciable increase in GGT expression. Moreover, cancer group exhibited remarkable increase in PCNA and Ki-67 expression. Furthermore, this group revealed no DNA fragmentation. Histopathological investigation of liver tissue sections in cancer group revealed typical anaplasia. In contrast, the treated groups showed significant depletion in the studied tumor markers and downregulation in GGT gene expression. Also, these groups displayed marked decrease in PCNA and Ki-67 expression. Carvacrol treated group revealed obvious DNA fragmentation. While, doxorubicin treated group displayed smear DNA patterns. Interestingly, treatment with carvacrol showed marked improvement in the histological feature of liver tissue. While, treatment with doxorubicin revealed no remarkable difference from the cancer group. This study indicated the promising therapeutic potential of carvacrol against hepatocellular carcinoma through its antiangiogenic, antiproliferative and apoptotic effects.

Keywords: Hepatocellular carcinoma, carvacrol, proliferation, apoptosis, angiogenesis, in vivo.


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