Effect of caffeic acid derivatives on polychlorinated biphenyls induced hepatotoxicity in male mice

Abstract

Chronic exposure to coplanar polychlorinated biphenyls (PCBs), a potent inducer of toxic reactive oxygen species (ROS), in the environment and food can cause liver diseases. It remains unknown whether caffeic acid derivatives (CADs) exerted protective effect on PCB-induced hepatotoxicity. We sought to evaluate the activities of 3 CADs on PCB169-induced oxidative stress and DNA damage in the liver. Male ICR mice were administered with 1 μmol/mL PCB169 at 5 mL/kg body weight for 2 weeks. The mice were given CADs by gastric gavage for 3 weeks. We found that PCB169 decreased the growth rate and reduced the levels of superoxide dismutase (SOD), glutathione (GSH) and GSH peroxidase (GPx). It increased the liver weight, malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels and CYP1A1 activity in the liver tissues and plasma of mice (P<0.05). Pretreatment of mice with CADs restored the above parameters to normal levels. There was a synergistic protective effect between CADs in preventing MDA and 8-OHdG formation and inducing CYP1A1 and phase II metabolism enzyme (SOD, GPx) activities (P<0.05). In conclusion, PCB169 induced hepatotoxicity and pretreatment with CADs had synergistic protective effects on liver damage.

Molecular mechanisms linking environmental toxicants to cancer development: Significance for protective interventions with polyphenols

“…Notably, PCB exposure in mice with compromised liver worsen overall inflammation as suggested by increased levels of circulating inflammatory biomarkers [195]. To ameliorate PCB and dioxin inflammatory mechanisms, hydroxycinnamic acids [268], quercetin [78,134], EGCG [80,83,135] and resveratrol [59,269] have shown positive effects.…”

Energy metabolic dysfunction as a carcinogenic factor in cancer cells

“…Moreover, growing evidence has shown that the mutation of ALDH2 involved in the oxidative pathway of alcohol metabolism can promote hepatocarcinogenesis in murine [ 30 ]. Polychlorinated biphenyls, which are potent inducers of toxic ROS, have been reported to be capable of inducing DNA damage and activating oxidative stress responses [ 31 ]. Besides the mutational events in chemical carcinogenesis, epigenetic alterations also affect the metabolism of cells and may be crucial for the development of cancer cells [ 32 , 33 ].…”

A Critical Review of Polychlorinated Biphenyls Metabolism, Metabolites, and Their Correlation with Oxidative Stress

“…148 This group also discovered that 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone and PCB169 could aggravate lipid peroxidation. 128,149 8-OHdG, the marker of oxidative DNA, was also detected in mouse hepatocytes upon PCB169 administration. 82 These DNA oxidative biomarkers were also observed in vitro upon Aroclor 1254, hydroxylated PCB, and PCB quinone challenges.…”

“…Similarly, strengthened TBARS was observed in higher concentration PCB101 exposed human lung fibroblast cells . This group also discovered that 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone and PCB169 could aggravate lipid peroxidation. , 8-OHdG, the marker of oxidative DNA, was also detected in mouse hepatocytes upon PCB169 administration . These DNA oxidative biomarkers were also observed in vitro upon Aroclor 1254, hydroxylated PCB, and PCB quinone challenges. ,− Unfortunately, the evidence of direct comparison of parent and daughter metabolites on the inducing of oxidative stress is limited …”