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

202127 citationsOpen accessKafr el-Sheikh University

In plain language

This study examines the protective effects and underlying mechanisms of the fungus Aspergillus awamori against chemically induced liver cancer initiation in male Wistar rats. Liver cancer was induced using diethylnitrosamine across seventy-two rats grouped to test various doses of the fungus. Administration of Aspergillus awamori significantly alleviated the toxic effects of diethylnitrosamine. It restored white blood cell profiles to normal and lowered elevated liver damage markers, including aspartate aminotransferase, alanine transaminase, alkaline phosphatase, and gamma-glutamyl transferase. The fungal treatment enhanced antioxidant defences by boosting reduced glutathione levels and catalase activity, while reducing malondialdehyde, a marker of oxidative stress. Furthermore, it suppressed pre-cancerous liver lesions, inhibited Cyp19 gene expression, and upregulated the tumour suppressor gene p53. These findings indicate that Aspergillus awamori exerts hepato-protective and chemo-preventive actions against the early stages of liver carcinogenesis.

Key takeaways

  • Aspergillus awamori reduced markers of liver injury and normalised blood counts in rats exposed to a cancer-inducing chemical.
  • The treatment boosted antioxidant defences by increasing glutathione levels and catalase activity while reducing malondialdehyde.
  • Administration of the fungus suppressed the formation of pre-cancerous GST-P-positive liver foci.
  • The protective response was linked to the downregulation of the Cyp19 gene and the activation of the p53 tumour suppressor gene.

Why it matters

Liver cancer is among the most prevalent and difficult malignancies to treat globally. Understanding natural substances that can protect liver tissue and intervene during the earliest phases of tumour development offers new directions for disease prevention. Demonstrating that a fungal supplement can reduce oxidative stress and alter key cancer-related genes provides a foundation for exploring alternative preventive approaches against liver cancer.

Commercialisation angle

The research points towards potential applications in preventive healthcare, nutraceuticals, or adjunct therapeutic formulations targeting liver health and cancer prevention. Pharmaceutical and dietary supplement developers could explore Aspergillus awamori extracts as chemo-preventive agents. However, this is early-stage animal research conducted in rats, meaning substantial further investigation, including active compound identification, safety assessments, and human clinical trials, is required before any real-world products can emerge.

AI-generated from the published abstract. Always read the original work before citing.

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 <i>Aspergillus awamori</i> (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 <i>A. awamori</i> 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 (<i>Cyp19</i>) and activating <i>p53</i> gene expression. In conclusion, supplementation of <i>A. awamori</i> 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 <i>A. awamori</i> in induced hepatocarcinogenesis.

Research topics

  • Genomics, phytochemicals, and oxidative stress
  • Cancer Research and Treatments
  • Cancer, Hypoxia, and Metabolism

Sustainable Development Goals

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DOI: 10.3390/antiox10060922

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