SIRT1‐mediated amelioration of oxidative stress in kidney of alcohol‐aflatoxin‐B1‐induced hepatocellular carcinoma by resveratrol is catalase dependent and GPx independent

Abstract

Hepatocellular carcinoma (HCC) is a type of primary liver cancer and dietary exposure to aflatoxins is a major risk factor of HCC. The current study aimed to assess the role of resveratrol and nicotinamide in renal toxicity during alcohol‐aflatoxin‐B1‐induced HCC. The results revealed that resveratrol treatment normalized the level of urea, lipid peroxidation, lactate and lactate dehydrogenase, which were increased in HCC. It also downregulated the increased expression of sirtuin 1 in HCC kidney. Furthermore, amelioration of oxidative stress in kidney of HCC rats by resveratrol was observed to be catalase dependent and glutathione peroxidase independent.

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

“…Resveratrol is an established ROS scavenger and studies have shown that it enhances the expression of CAT, peroxidase, superoxide dismutase, and GSH by maintaining the redox status of the cell. [ 14,22 ] Few reports have suggested regulation of CAT by NF‐κB; CAT being downregulated when canonical NF‐κB activation occurs. [ 35 ] In the present study, we could see there is an upregulation of NF‐κB, thereby resulting in the downregulation of CAT in HCC (Figure 7) and (Figure 3).…”

“…Reports suggest that resveratrol is a natural activator of SIRT1. [ 22,45 ] Sometimes resveratrol does not act as a direct activator of SIRT1, and different mediators may be involved in the mechanism. [ 46 ] In an animal model of diethylnitrosamine‐induced HCC, resveratrol has been reported to upregulate SIRT1 activity via AMP‐activated protein kinase.…”

“…GPx activity was measured as described earlier with slight modification. [ 21,22 ] Briefly, the assay mixture consisted of 0.17 mM GSH, 100 mM Tris‐Cl pH 7.2, 0.5 mM NADPH, 0.25 mM H 2 O 2 , 1 U GR, and appropriately diluted tissue extract was incubated at 37°C for 10 minutes. One millimolar sodium azide was mixed with the solution to stop the CAT activity.…”

“…The activity of GR was determined as described previously with slight modification. [ 22,23 ] Briefly, the reaction mixture consisted of 0.2 M phosphate buffer (pH 7.0), 0.2 mM EDTA, 1 mM GSSG, 0.2 mM NADPH, and suitably diluted tissue extract. NADPH oxidation was measured as a decrease in OD at 340 nm for 5 minutes.…”

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

“…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 ].…”