Modulation of antioxidant enzymes, SIRT1 and NF‐κB by resveratrol and nicotinamide in alcohol‐aflatoxin B1‐induced hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed cancer worldwide and is associated with poor prognosis. The current study aimed to assess the therapeutic efficacy of resveratrol when administered alone and in combination with nicotinamide against alcohol‐aflatoxin B1‐induced HCC. Results reveal that during the development and progression of cancer, there was a decline in the level of antioxidant enzymes catalase, glutathione peroxidase, glutathione reductase (GR), antioxidant glutathione, and glutathione S‐transferase, which is an enzyme of detoxification pathways. Treatment of resveratrol restored the level of catalase and glutathione peroxidase toward normal in alcohol‐aflatoxin B1‐induced HCC; however, nicotinamide worked in concert with resveratrol only in upregulating the activity of glutathione reductase, glutathione level, and glutathione S‐transferase. SIRT1 agonist resveratrol was observed to modulate the activity of antioxidant enzymes by negatively regulating the expression of nuclear factor‐κB (NF‐κB) in alcohol‐aflatoxin B1‐induced HCC, thereby suggesting a cross‐talk between antioxidant enzymes SIRT1 and NF‐κB during the development and progression of HCC and its therapeutics by resveratrol and nicotinamide.

Discovering the Protective Effects of Resveratrol on Aflatoxin B1-Induced Toxicity: A Whole Transcriptomic Study in a Bovine Hepatocyte Cell Line

“…For this reason, to prevent or mitigate aflatoxicosis in farmed animals, the use of feed additives, consisting of botanical extracts with known antioxidant capacities, is a viable option. For instance, the efficacy of curcumin has been widely tested [ 21 , 22 , 23 , 24 , 25 ]; besides curcumin, several natural polyphenols have also been investigated, providing encouraging results [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Among them, the use of resveratrol (R) represents a promising strategy.…”

“…Recently, the potential anti-AFB1 activity of R has been explored in rodents. In alcohol-AFB1-induced rat hepatocellular carcinoma, a two-week treatment with R (100 mg/kg bw) restored the level of key antioxidant enzymes (i.e., SIRT1, CAT, and GPX) toward normal levels [ 30 , 58 ]. In mice, R decreased AFB1-induced ROS accumulation, ameliorated adverse hepatic functions by increasing hepatic antioxidant capacity and inhibiting the expression of cleaved-caspase-3 protein [ 59 ].…”

Phytochemicals as an Alternative or Integrative Option, in Conjunction with Conventional Treatments for Hepatocellular Carcinoma

“…Additionally, resveratrol has been shown to inhibit HCC proliferation, migration, and invasion through downregulation of membrane-associated ring-CH-type finger 1 (MARCH1), an E3 ubiquitin ligase typically found to be heavily upregulated in HCC [93]. Resveratrol treatment, when administered orally to rats with HCC at a dose of 100 mg/kg for 2 weeks, restored the antioxidant enzymes catalase and glutathione peroxidase to normal levels, as these are typically downregulated in HCC [94]. A resveratrol diet fed to Sprague Dawley rats (at a dose of 300 mg/kg) was shown to reduce nitric oxide production in the liver through inducible nitric oxide synthase downregulation [95].…”

Biochemical Mechanisms Associating Alcohol Use Disorders with Cancers.

“…Control of microbiome [13,[341][342][343][344][345] The hub of one-carbon metabolism Colorectal and other tissues.…”