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

Abstract

Hepatocellular carcinoma (HCC) is the most common cancer in humans. Despite advances in its treatment, liver cancer remains one of the most difficult cancers to treat. This study aimed to investigate the ameliorative action and potential mechanism of Aspergillus awamori (ASP) administration against the initiation process of liver carcinogenesis induced by diethylnitrosamine (DEN) in male Wistar rats. Seventy-two male rats were divided equally into eight groups as follows, Group 1: untreated control; Group 2: DEN (200 mg/kg bw) intra-peritoneally for the initiation of HCC; Groups 3–5: DEN + ASP at a dose of 1, 0.5, and 0.25 mg/kg bw and groups 6–8: ASP at a dose of 1, 0.5, and 0.25 mg/kg bw. Supplementation of A. awamori significantly lightened the adverse impacts induced by DEN via restoring the leukogram to normal, lowering the elevated serum aspartate aminotransferase (AST), alanine transaminase (ALT), and γ-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Furthermore, it enhanced the hepatic antioxidant capacity through increasing the reduced glutathione (GSH) level and catalase (CAT) activity with a marked reduction in malondialdehyde (MDA) level. In addition, it decreased the positive GST-P foci. Likewise, a significant alteration of DEN-associated hepatocarcinogenesis occurred through inhibiting cytochrome P450 (Cyp19) and activating p53 gene expression. In conclusion, supplementation of A. awamori counteracts the negative effects of DEN, inhibits the early development of GST-P-positive foci and could be used as a new alternative strategy for its chemo-preventive effect in liver cancer. To the best of our knowledge, the present study is the first to report the hepato-protective effect of A. awamori in induced hepatocarcinogenesis.

Arthrospira platensisnanoparticles defeat against diabetes‐induced testicular injury in rat targeting, oxidative, apoptotic, and steroidogenesis pathways

“…Rats were randomly divided into eight groups. Group 1 is untreated rats (control), Group 2 including STZ‐induced diabetic rats with 65 mg/kg body weight STZ (STZ‐diabetic), Group 3–5: including diabetic rats treated with NSP1, NSP2, and NSP3 at 0.25, 0.5, and 1 mg/kg body weight respectively, once daily orally (Assar et al, 2021) by the aid of gastric gavage for 12 consecutive weeks and groups 6–8 include normal rats received NSP (0.25, 0.5, and 1 mg/kg body weight once daily orally. The identical volume of normal saline was injected into both control and diabetic rats.…”

Chemoprotective Effect of Decalactone on Hepatic Cancer via Diminishing the Inflammatory Response and Oxidative Stress

“…According to a previous study, oxidative stress has a significant role in the progression of hepatic cancer 5,31) . DEN causes the production of free radicals, which react with lipids, causing LPO to be produced and the progression of hepatic cancer to begin 5,6) .…”

“…The progression of HCC, after the liver cirrhosis and chronic hepatitis. The major cause for development of HCC is chronic hepatitis (B and C) alcohol abuse, non-alcoholic steatohepatitis and viral infection non-alcoholic fatty liver 5,6) . Moreover, other hepatic diseases include Wilson s disease, α-1 antitrypsin deficiency and hemochromatosis are shows a crucial role in the initiation and progression of HCC.…”

“…DEN showed the direct effect on DNA alkylating and start the generation of reactive oxygen species (ROS) , after its bioactivation via cytochrome P450 (CYP450) enzyme in the hepatic tissue 3,4) . Additionally, long treatment of DEN increases the hepatocytes necrotic death-inflammation-regeneration and eventually cirrhosis and fibrosis in human 5,16) .…”

Linoleic acid pathway disturbance contributing to potential cancerization of intrahepatic bile duct stones into intrahepatic cholangiocarcinoma

“…On the other hand, ALP as a marker of terminal differentiation can be involve into multiply cell activities, such as differentiation and cycle regulation [ 37 – 39 ]. Its abnormal increase previously be reported as an indicator for hepatocarcinogenesis and prognosis [ 40 , 41 ]. Consequently, long-term monitoring of metabolites from linoleic acid metabolism pathway and protein indicators of liver function in IBDS patients has important guiding significance for the monitoring of IBDS carcinogenesis.…”