Null anticarcinogenic effect of silymarin on diethylnitrosamine-induced hepatocarcinogenesis in rats

Abstract

The aim of this study was to investigate the anticarcinogenic effects of silymarin in diethylnitrosamine (DEN)-induced hepatocarcinogenic rat models. Severe and mild models of hepatocellular carcinoma (HCC) were generated by the intraperitoneal administration of 40 mg/kg DEN once a week for 18 weeks and 100 mg/kg DEN every 2 weeks for 6 weeks in male Wistar rats, respectively. In the severe and mild models of HCC, the rats were treated with 0.1 and 0.5% silymarin for 18 weeks and with 0.1% silymarin for 5 weeks, respectively. Serum transaminase levels were not significantly decreased by the silymarin treatment in either model. Macroscopic and microscopic features indicated that the silymarin-containing formulations did not significantly inhibit the hepatic tumor formation induced by DEN. Furthermore, immunohistochemical and western blot analyses demonstrated that the expression levels of proliferating cell nuclear antigen and glutathione S-transferase P, which are hepatocarcinogenic markers, were not significantly modified by the silymarin treatment. These results indicate that silymarin may not be considered as a candidate agent against hepatocarcinogenesis.

Melatonin Activates Endoplasmic Reticulum Stress and Apoptosis in Rats with Diethylnitrosamine-Induced Hepatocarcinogenesis

“…Administration of melatonin to DEN-treated animals indicated that the indole was able to reduce hepatocarcinogenic features in HCC-bearing rats, because it ameliorated histology, and reduced changes in serum enzymes and in the expression of GST-P, a protein considered a marker of hepatocarcinogenesis[ 36 ]. These findings are in accordance with results by different authors that also used DEN as a HCC promoter and tested effects of melatonin or other antioxidants, such as resveratrol, maotai or daffron, in rats [ 24 , 37 – 40 ] and mice [ 41 ]. Melatonin also prevented DNA damage in DEN-treated animasl, probably due to its capacity to regulate several key genes involved in DNA repairing pathways, such as CEP152 and N4BP2L2 [ 42 ].…”

Protective Effect of Fish Oil and Virgin Olive Oil on Diethylnitrosamine Toxicity in Rats

“…These results may attribute to the presence of omega-3 fatty acids of fish oil and virgin olive oil which had important beneficial effects on the liver regeneration. [48] who reported that rats feeding silymarin with injected DEN were significantly decreased liver function. Meanwhile, Feeding on ration mixed with fish oil, virgin olive oil and mixed with fish oil and virgin olive oil at concentration 5g/100g diet for 60 successive days did not induce changes of serum total protein, albumin and total bilirubin when compared with control normal group.…”

Milk Thistle (Silybum Marianum) as a Supportive Phytotherapeutic Agent in Oncology

“…Minimálně jedna studie na potkanech, u kterých byl vznik HCC modelován pomocí DENA, ale protektivní vliv silymarinu nepotvrdila [11]. Další studie na stejném modelu prokázala jenom okrajový hepatoprotektivní účinek silymarinu v raném stadiu vývoje tumoru, ale současná podání ethanolu a silymarinu u myší s rozvinutým HCC způsobila progresi ná-doru.…”