Sake lees hydrolysate protects against acetaminophen-induced hepatotoxicity via activation of the Nrf2 antioxidant pathway

Abstract

Acetaminophen is a commonly used analgesic. However, an overdose of acetaminophen causes severe hepatotoxicity via depletion of hepatic glutathione. Here, we investigated the protective effects of sake lees hydrolysate against acetaminophen-induced hepatotoxicity in mice. Sake lees hydrolysate was administered orally to ICR mice for seven days. Six hours after acetaminophen treatment, the mice were sacrificed, and blood and liver samples were collected for analysis. Treatment with acetaminophen markedly increased the levels of serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase. Pretreatment with sake lees hydrolysate significantly prevented the increases in the serum levels of these enzymes and inhibited acetaminophen-mediated glutathione depletion. In addition, histopathological evaluation of the livers also revealed that sake lees hydrolysate prevented acetaminophen-induced centrilobular necrosis. The expression of γ-glutamylcysteine synthetase (γ-GCS), hemeoxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the liver were decreased after acetaminophen treatment, whereas pretreatment with sake lees hydrolysate led to an increased expression of all three proteins. Furthermore, sake lees hydrolysate induced the expression of these proteins in HepG2. These results suggested that sake lees hydrolysate could induces HO-1 and γ-GCS expression via activation of the Nrf2 antioxidant pathway, and protects against acetaminophen-induced hepatotoxicity in mice.

Protective Effects of Rice Peptide Oryza Peptide-P60 against Oxidative Injury through Activation of Nrf2 Signaling Pathway In Vitro and In Vivo

“…028-002), and the study was conducted according to the Animal Experimentation Guidelines of Shujitsu University. The procedures were performed as described in our previous publications. , Mice were randomly divided into five groups. The rice peptide groups were orally administered OP60 (250 or 500 mg/kg body weight) via a stomach tube daily for 7 days, whereas the control and APAP groups were administrated saline.…”

“…17 Additionally, rice-derived peptides and sake lees hydrolysate are hepatoprotective in the case of acetaminophen (APAP)-induced liver injury. 18,19 These antioxidative effects were suggested to be mediated through the Nrf2 antioxidant pathway. However, only a few peptides have been shown to act as indirect antioxidants by regulating the oxidative defense systems.…”

Isolation of the hemeoxygenase-1 inducer from rice-derived peptide

“…HO-1 expression contributes to protection against APAP-induced liver damage.‍ ( 12 ) In previous reports, sulforaphane,‍ ( 36 ) sake lees hydrolysate,‍ ( 37 ) and salvianolic acid C ‍ ( 38 ) have protective effects against APAP-induced hepatotoxicity through antioxidant effects mediated via HO-1 induction. We previously reported that RP protects against APAP-induced hepatotoxicity in mice.‍ ( 22 ) Our results indicate that RSAVLLSH derived from RP may be an active peptide with a hepatoprotective effect via the induction of HO-1 expression.…”

Hepatoprotective Activity of Yellow Chinese Chive against Acetaminophen-Induced Acute Liver Injury via Nrf2 Signaling Pathway

“…The main function of HO-1 is to degrade heme and generate carbon monoxide (CO) and biliverdin which are both powerful antioxidants (36). According to previous reports, sulforaphane (37), sake lees hydrolysate (38), and salvianolic acid C (34) play protective roles against APAP-induced hepatotoxicity though antioxidant effects mediated by HO-1 induction. YCE induced HO-1 expression in mice livers (Fig.…”