Chlorogenic acid prevents acetaminophen-induced liver injury: The involvement of CYP450 metabolic enzymes and some antioxidant signals

Abstract

Chlorogenic acid (CGA), a polyphenolic compound, is abundant in fruits, dietary vegetables, and some medicinal herbs. This study investigated the prevention of CGA against acetaminophen (AP)-induced hepatotoxicity and its engaged mechanisms. CGA reversed the decreased cell viability induced by AP in L-02 cells in vitro. In addition, CGA reduced the AP-induced increased serum levels of alanine/aspartate aminotransferase (ALT/AST) in vivo. The effect of CGA on cytochrome P450 (CYP) enzymatic (CYP2E1, CYP1A2, and CYP3A4) activities showed that CGA caused very little inhibition on CYP2E1 and CYP1A2 enzymatic activities, but not CYP3A4. The measurement of liver malondialdehyde (MDA), reactive oxygen species (ROS), and glutathione (GSH) levels showed that CGA prevented AP-induced liver oxidative stress injury. Further, CGA increased the AP-induced decreased mRNA expression of peroxiredoxin (Prx) 1, 2, 3, 5, 6, epoxide hydrolase (Ephx) 2, and polymerase (RNA) II (DNA directed) polypeptide K (Polr2k), and nuclear factor erythroid-2-related factor 2 (Nrf2). In summary, CGA ameliorates the AP-induced liver injury probably by slightly inhibiting CYP2E1 and CYP1A2 enzymatic properties. In addition, cellular important antioxidant signals such as Prx1, 2, 3, 5, 6, Ephx2, Polr2k, and Nrf2 also contributed to the protection of CGA against AP-induced oxidative stress injury.

The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state

“…However, increasing the levels of antioxidant enzymes by activating Nrf2 may not be sufficient to decrease oxidative/nitrosative stress and chronic inflammation optimally, because antioxidants, which are decreased in a high oxidative environment, must also be elevated. Recently, it was reported that Nrf2 provides a new therapeutic target for treatment of diabetic retinopathy and acetaminophen-induced liver injury [ 45 , 46 ].…”

Therapeutic Potential of Plants and Plant Derived Phytochemicals against Acetaminophen-Induced Liver Injury

“…Zheng et al (2015) showed its hepatoprotective effect by the inhibition of pro-inflammatory cytokines, MPO expression and activity, restoration of liver enzymes and salvage of liver tissues along with diminution of raised expression of TLR-3, TLR-4 and MyD88 and the increased phosphorylation of inhibitor of kappa B (IκB) and p65 subunit of NF-κB in liver [53]. Further, it also improved cell viability in L-02 cells and showed the inhibition of activities of CYP2E1 and CYP1A2 in addition to improved antioxidant signals against APAP-induced cytotoxicity [54].…”

Antioxidant and antidiabetic properties of tartary buckwheat rice flavonoids after in vitro digestion

“…Oxidative stress is a notorious factor in the development of degenerative and age-related diseases such as diabetes (Lee et al, 2007;Hosaka et al, 2011;Yu et al, 2015), cancer (Lee et al, 2013;Zhu, 2016), immunity (Yu et al, 2016), liver injury (Zhang et al, 2014;Pang et al, 2015), cardiovascular (Andriantsitohaina et al, 2012) and neurodegenerative diseases (Choi et al, 2015). Oxidative stress-induced perturbations in the antioxidant defence systems of the body lead to DNA damage and cellular dysfunction, which is further linked to diabetes.…”