Protective effects of Persea americana fruit and seed extracts against chemically induced liver cancer in rats by enhancing their antioxidant, anti-inflammatory, and apoptotic activities

Abstract

This study aims to explore the chemopreventive mechanisms of hydroethanolic extracts from avocado (Persea Americana) in diethylnitrosamine (DEN)/2-acetylaminofluorene (2AAF)-induced hepatocarcinogenesis. Chemical induction of hepatocarcinogenesis was induced by intraperitoneal injection of DEN at 150 mg/kg body weight (b.w.) twice a week for a fortnight, followed by oral administration of 2AAF at 20 mg/kg b.w. four times a week for 3 weeks. Rats administered DEN/2AAF were orally treated with hydroethanolic extracts of avocado fruits and seeds at a dose of 50 mg/kg b.w. every other day for 20 weeks. Moreover, rats administered DEN/2AAF and treated with avocado extracts revealed a marked decrease in liver enzyme activities, total bilirubin levels, and elevated liver tumor markers, but revealed an increase in total protein and albumin levels. The hepatocytes with hyperchromatic and bile duct cystadenoma observed in the liver of rats administered DEN/2AAF were reduced due to treatment with avocado extracts. Furthermore, the treatments prevented the elevation of lipid peroxidation levels and ameliorated the lowered glutathione peroxidase, glutathione-S-transferase, superoxide dismutase activities, and glutathione content in the liver tissues. Also, antigen Ki-67, cyclooxygenase-2, and nuclear factor kappa-B expression levels were decreased, but of the suppressor proteins p53 and BAX levels were increased in the liver of rats administered DEN/2AAF and treated with avocado extracts. In conclusion, the current results demonstrated that avocado extracts could abate hepatocarcinogenesis in rats administered DEN/2AAF through activation of antioxidant, anti-inflammatory, and apoptotic properties.

Rutin and Quercetin Counter Doxorubicin-Induced Liver Toxicity in Wistar Rats via Their Modulatory Effects on Inflammation, Oxidative Stress, Apoptosis, and Nrf2

“…Oxidative stress, inflammation, and apoptosis suppression by treatments with rutin and quercetin attribute to the amelioration of liver function and structural integrity (Scheme 2). The present investigation found that DXR-injected animals exhibited elevated levels of serum total bilirubin, which is similar with the results of Liss et al [70], Ahmed [71], Hozayen et al [60], Hassan et al [67], Ahmed et al [68], and Ahmed et al [72]. These researchers argued that it is a clear indicator of liver disease and may be caused by bile ductile occlusion induced by portal triad inflammation and fibrosis and/or conjugated bilirubin reflux from necrotic hepatocytes to sinusoids.…”

Preventive Effects of Mandarin Fruit Peel Hydroethanolic Extract, Hesperidin, and Quercetin on Acetaminophen-Induced Hepatonephrotoxicity in Wistar Rats

“…In the present study, both proteins increased significantly in NAPAP-administered rats and the treatment with MPHE, hesperidin, and quercetin significantly reduced these NAPAP-induced elevations reflecting the antiapoptotic effects of MPHE, hesperidin, and quercetin (Figure 8). It is worth mentioning that p53 is an important mediator of intrinsic apoptosis [123,124], and the activation of caspase 3 can be mediated by stimulation of both intrinsic and extrinsic pathways of apoptosis [36]. Moreover, TNF-α may activate the extrinsic pathway by binding to tumor necrosis factor receptors (TNFR) on the cell membrane [36] (Figure 8).…”

The anticarcinogenic effect of eugenol on lung cancer induced by diethylnitrosamine/2-acetylaminofluorene in Wistar rats: insight on the mechanisms of action

“…The lungs are the most vulnerable organ for endogenous oxidants and ROS damage because they interact with the outside environment [ 35 ]. In experimental animals, DENA is a common and widely used chemical substance to induce esophageal, hepatic, and pulmonary malignancies [ 7 , 36 ]. In this study, we evaluated the chemopreventive effect of eugenol on DENA/AAF-induced lung cancer and determined its possible action mechanisms.…”