Caffeic acid phenethyl ester attenuates changes in pancreatic tissue damage biomarkers induced by cisplatin

Abstract

Application of cisplatin (CP) for the treatment of different cancers is known to cause pancreatitis through an increase in reactive oxygen species production and promotion of inflammation. Caffeic acid phenethyl ester (CAPE), the main activity carrier of propolis extracts, was previously found to possess numerous beneficial properties. This study aims to determine for the first time the potential of CAPE in preventing CP-induced pancreatic tissue damage by studying the changes occurring on both biochemical and microscopic levels. The levels of serum α-amylase and a panel of pancreatic tissue biomarkers related to tissue injury (reduced glutathione, xanthine oxidase, malondialdehyde, and protein carbonylated concentration) and inflammation (myeloperoxidase, nitric oxide, and umor necrosis factor alpha) were studied in male Wistar rats treated with either CP alone or with CP and CAPE. Additionally, microscopic analysis of pancreatic tissue would be conducted as well. Application of CAPE together with CP statistically significantly prevented the disturbance in all here-studied pancreatic tissue damage and inflammation-related biomarkers. The changes in pancreas biochemical status was followed by morphological disturbance. The results of the present study suggest that CAPE could act as a protective agent in pancreatic damage that arises after CP application.

A Nano-Liposomal Formulation of Caffeic Acid Phenethyl Ester Modulates Nrf2 and NF-κβ Signaling and Alleviates Experimentally Induced Acute Pancreatitis in a Rat Model

“…Oxidative stress has been demonstrated to play a cardinal role in the pathogenesis of AP [ 12 ]. In accordance with previous reports [ 6 , 53 ], rats with AP showed significantly diminished activity of glutathione reductase (GR), significantly decreased levels of glutathione (GSH), the endogenous antioxidant, and significantly elevated levels of malondialdehyde (MDA), the end product of lipid peroxidation. Induction of pancreatitis elicited a marked 69% and 37.5% decline in pancreatic GR activity and GSH content, respectively, and a notable 110% increase in the pancreatic level of MDA compared to the corresponding control values.…”

“…The histologically observed neutrophil infiltration in pancreatic tissue of rats in the ORN group is in accordance with previously reported infiltration of neutrophil granulocytes and monocytes 18 to 36 h after 3 g/kg L-ornithine injection [ 11 ]. Elevated pancreatic MPO activity was previously reported in several rat models of AP [ 11 , 20 , 53 ]. The enhanced neutrophil infiltration could be attributed to the intense inflammatory upsurge associated with pancreatitis as revealed by the observed NF-κB activation which, in turn, plays an important role in the activation of inflammatory mediators (ICAM-1, TNF-α) [ 8 ].…”

“…The beneficial effect of CAPE in AP and pancreatic injury has been previously demonstrated in vancomycin, cerulein and cisplatin-induced models [ 15 , 33 , 53 ] showing significant lowering of serum amylase and lipase activities, while no direct effect was reported for CAPE on serum amylase or lipase activities in normal rats [ 20 , 53 ]. However, no studies so far have addressed the possible benefit of incorporating CAPE into a nano-based formulation to enhance its oral bioavailability and hence its efficacy in any model of AP.…”

Caffeic acid phenethyl ester: A review on its pharmacological importance, and its association with free radicals, COVID‐19, and radiotherapy

“…The researchers stated that this activity of CAPE is most likely achieved by reducing the production of ROS and, as a result, inhibiting the production of inflammatory mediators that cause damage to cell‐building molecules. The results obtained from biomarkers at the biochemical/molecular level, as well as pathohistological analysis, also emphasize that they support these claims (Stošić et al, 2020).…”

Ginger juice prevents cisplatin‐induced oxidative stress, endocrine imbalance and NO/iNOS/NF‐κB signalling via modulating testicular redox‐inflammatory mechanism in rats

“…It unleashes its anticancer action through formation of cisplatin‐DNA adduct by intrastrand cross‐links due to interaction with cancer cell DNA purine bases eventually leading to p53 activation, cell cycle arrest and induction of apoptosis (Calcabrini, Maffei, Turrini, & Fimognari, 2020; Dasari & Bernard Tchounwou, 2014). Despite its potent antineoplastic efficacy, the constraint to its clinical utility is the development of organ toxicity, including nephrotoxicity, neurotoxicity, hepatotoxicity, myelosuppression, cardiotoxicity, pancreatic and testicular damage (Bami et al., 2017; Bilgic et al., 2018; El‐Hawwary & Omar, 2019; Stošić et al., 2020). In the emerging papers, CIS‐induced damage to testes and hormonal imbalance has been suggested a chief side effect because it has been clinically associated with infertility (Altuner, Gulaboglu, Yapca, & Cetin, 2013; Mercantepe, Unal, Tümkaya, & Yazici, 2018; Sabanegh & Ragheb, 2009).…”