Amelioration of diethylnitrosamine (DEN)-induced hepatocellular carcinogenesis in animal modelsviaknockdown oxidative stress and proinflammatory markers byMadhuca longifoliaembedded silver nanoparticles

Abstract

In hepatocellular carcinoma (HCC), primary liver cancer is primarily responsible for inflammation-related cancer as more than 90% of HCCs emerge with regard to hepatic damage and inflammation. Tenacious inflammation is known to advance and intensify liver tumours. Nanomaterials, for example, silver nanoparticles synthesized from plant-derived materials have shown great outcomes in reducing the precancerous nodules and have anticancer properties. The aim of the present investigation was to biosynthesize, characterize and evaluate the anticancer activity of nanoparticles-embedded Madhuca longifolia extract (MLAgNPs) on an experimental model of hepatic cancer in rats. M. longifolia contains a high amount of flavonoids and other phenolic derivative. The silver nanoparticles synthesized by M. longifolia were characterized by various instruments, including UV-Vis spectrophotometry, X-ray beam diffraction, field-emission scanning electron microscopy with energy dispersive X-ray analysis, transmission electron microscopy and Fourier transform infrared spectroscopy. Liver cancer was induced to 36 Wistar rats by a single dose of diethylnitrosamine (DEN) (200 mg kg À1 BW). Hepatic cancer byMLAgNPs dose-dependently limited macroscopical variation compared with the DEN-induced hepatic cancer groups. The serum and liver were taken to measure the antioxidant parameters, proinflammatory cytokines and for a histopathological study. Serum hepatic and serum non-hepatic along with inflammatory cytokines were also assessed. Reduction in the levels of proinflammatory cytokines, namely tumour necrosis factor-a, interleukin-6, interleukin-1b, nuclear factor kappa beta (NF-kB), and improved membrane-bound enzyme activity were also detected. It was found that minor morphological anomalies were identified in the histopathology analysis in the MLAgNPs-treated groups. It could be concluded that silver nanoparticles introduce an extraordinary potential for use as adjuvants in hepatic cancer treatment because of their antioxidant abilities and ability to diminish inflammation in liver tissue by attenuating the NF-kB pathway.

The Apoptotic Effect of Trichinella spiralis Infection Against Experimentally Induced Hepatocellular Carcinoma

“…The mean body weight of HCC group (group III) was less than the other three groups with no stastistically significant reduction that might be related to the toxic effect of CCL4 and DEN and the decrease of the appetite. Similar studies related to HCC reported body weight reduction and tissue destruction (Singh et al, 2018;Badr El-Din et al, 2020) as compared to the control group.…”

“…The mean wet liver weight of rats with HCC (group III) and HCC-T. spiralis (group IV) was increased with the time of the experiment with higher increase in group III on the 40 th day from the onset of tumor formation. This increase might be explained by the effect of DEN on the liver as mentioned by JO et al, (2016) and Singh et al, (2018) who stated that treatment with DEN to induce HCC caused increasing in the liver weight. Meanwhile, the reduced liver weight in group IV as compared to group III suggested that the enlargement of the liver caused by DEN might be diminished by effect of T. spiralis infection.…”

“…These results coincide with many other studies that investigated the histopathological changes in DEN-induced HCC. Tolba et al, (2015) and Singh et al, (2018) demonstrated that the DEN-induced liver cancer group revealed an irregular cellular structure with divided nuclei, which had lost their spherical shapes. Cui et al, (2018) established a steatohepatitis-HCC mouse model using DEN.…”

Ameliorative Effects of Aspergillus awamori against the Initiation of Hepatocarcinogenesis Induced by Diethylnitrosamine in a Rat Model: Regulation of Cyp19 and p53 Gene Expression

“…Group 1 Normal control untreated rats fed with standard diet and administered orally with 0.5 mL normal saline by gastric intubation. Group 2 Rats were injected with DEN to induce hepatocarcinogenesis by providing a single dose of intraperitoneal injection (i.p) of DEN (200 mg/kg BW) on the first day of the experiment [27].…”

Promotive action of 2-acetylaminofluorene on hepatic precancerous lesions initiated by diethylnitrosamine in rats: Molecular study

“…DEN is used to induce precancerous and cancerous lesions. It is metabolically activated by the liver cytochrome cytochrome P450 (CYP450) system, followed by induced DNA damage and oxidative stress in hepatocytes during cancer initiation[ 18 ]. The drawback of this model is the duration required for appropriate tumor development[ 19 ].…”