Hepatoprotective Mechanism of Apigenin via Suppression of Oxidative Inflammatory Signaling and Apoptosis against Hepatotoxicity Induced by CCl4 in Rats

Abstract

Background: Carbon tetrachloride (CCl4) is a critical hepatotoxicant causing liver injury and fibrosis via hepatic production of reactive oxygen species (ROS). Apigenin (APG) is a natural bioactive compound and flavonoid antioxidant. We, therefore, evaluated whether APG could mitigate CCl4-mediated hepatotoxicity. Methods: Rats were randomly divided and administered APG and/or CCl4 in Control group, CCl4 group, APG + CCl4 groups (APG: 10 and 20 mg/kg bw) and APG groups (APG: 10 and 20 mg/kg bw) 2 times per week for 7 consecutive weeks. Result: Rats exposed to CCl4 demonstrated marked increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and monoamine oxidase (MAO) activities and decreased hepatic malondialdehyde (MDA) level compared to control. The hepatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) decreased appreciably. The CCl4 intoxication caused significant increases in inflammatory cytokines (IL-6 and TNF-α) and apoptosis markers, while the anti-inflammatory cytokines (IL-4 and IL-10) decreased with evident histopathological lesions compared to control. APG-dose-dependently-prevented these hepatic alterations.

Geraniol prevents CCl4-induced hepatotoxicity via suppression of hepatic oxidative stress, pro-inflammation and apoptosis in rats

“…Furthermore, the markers of hepatic protein synthetic capacity, ALB and TP, were markedly reduced in comparison to the control ( Table 1 ). It therefore corroborates the earlier reports that CCl 4 is an hepatotoxicant [1] , [22] , [3] , [8] . The liver is involved in the catabolism of drugs and xenobiotics.…”

“…Following the existing reports, CCl 4 oxidative stress causes activation of inflammatory and apoptotic cascades. CCl 4 action stimulates nuclear factor-kappa B (NF-κB), a nuclear transcriptional factor implicated in the expression of inflammatory cytokines and caspase-dependent apoptosis in liver damage [1] , [26] , [31] , [34] . To this end, we evaluated the effect of CCl 4 on pro-inflammatory (IL-6 and TNF-α), anti-inflammatory (IL-4 and IL-10) cytokines and caspase markers of apoptosis.…”

“…This result shows that CCl 4 provoked pro-inflammation and reduces anti-inflammation [25] , [28] . NF-κB is translocated to the nucleus during cellular oxidative stress in the hepatic tissue [4] , and its nuclear effect in terms of cytokine gene expression has been reported during CCl 4 hepatotoxicity [1] , [25] . In addition, we found histological infiltration of inflammatory cells ( Fig.…”