الفهرس 
Hepatocellular carcinomaOnly 14 pages are availabe for public view
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Abstract
RNA editing is an integral process in generating the diversity of cellular RNA signatures. The best characterized type of RNA editing is A to I (adenosine to inosine) that catalyzed by the ADAR family proteins. HCC is a heterogeneous tumor displaying variable genetic and epigenetic changes. In HCC, aberrant RNA editing may lead to tumor specific transcriptome diversity. Recently, the nutri-epigenomic studies are focusing on the beneficial changes of dietary agent such as pterostilbene on gene expression through epigenetic modifications. However, the effect of pterostilbene on ADAR enzymes expression or RNA editing in HCC has not been investigated.
The aim of our work was to investigate the effect of pterostilbene on hepatic gene expression of Adars in DEN-induced rat model of HCC. We assessed the potential effects of pterostilbene at two levels; “co-exposure chemo-prevention” in which pterostilbene was co administered with DEN from the first week of the study and “post-exposure chemo-prevention” in which pterostilbene treatment started after the onset of the key DEN-induced histopathological changes.
The current study was conducted at Medical Biochemistry Department, Faculty of Medicine, Ain Shams University from October 2018 to March 2019.
Our results revealed that DEN-induced hepatocarcinogenesis indicated by the appearance of prominent hepatic nodules with loss of hepatic architecture and appearance of malignant hepatocytes exhibiting marked pleomorphism, high nucleo-cytoplasmic ratio, prominent nucleoli and frequent mitotic figures. Regarding pterostilbene administration, it attenuates DEN-induced hepatocarcinogenesis; pterostilbene-treated groups exhibited an improvement of the hepatic architecture and minimal atypia of hepatocytes compared to their respective untreated HCC group.
Noteworthy, untreated HCC group exhibited a significant increase in Adar1 alongside a decrease in Adar2 relative expression levels. While pterostilbene treated groups had lower expression of Adar1 and higher expression of Adar2 in comparison to untreated HCC groups. Therefore, we thought that pterostilbene could alleviate the disrupted A-to-I editing enzymes and the prominent effect was in HCC rats received pterostilbene in 6th week of the study “post-exposure effect” in comparison to the group receiving Pterostilbene with DEN from the start of the study.
As expected, liver enzymes and AFP levels were higher in untreated HCC rats, while serum albumin level was lower compared to the control group (p<0.05). In the present study, pterostilbene treatment attenuates DEN-induced hepatocarcinogenesis; pterostilbene-treated groups exhibited a significant reduction in liver enzymes and AFP with improvement of serum albumin reflecting improvement of the synthetic function of the liver.
This study demonstrated that pterostilbene administration had no effect in non-HCC rats either at histological or biochemical levels, or relative expression of ADARs comparing to the control group.
The salient results revealed a positive significant correlation between the relative expression of Adar1 and liver weight, liver enzymes, and AFP while a negative significant correlation with serum albumin was detected (p<0.05). The hepatic expression of Adar2 had a negative significant correlation with transaminases and AFP (p<0.05). On the other hand, no significant correlation was detected between the expression of Adar2 and liver weight and serum albumin.