Reduction of Hepatotoxicity Induced by Doxorubicin

Abstract

Doxorubicin (DOX) has been used in the treatment of variety of cancers but its administration is limited by a dosedependent toxicity. Its cytotoxic effects on malignant cells have shown an increase in the risk of cardiotoxicity, hepatoxicity, renal insufisance.Antioxydants have been explored for both their cancer preventive properties and chemodulatory of DOX toxicity. Resveratrol (RSV) is a polyphenolic constituent of several dietary mainly of grapes and wine origin recently its anticancer potential has been extensively explored, revealing its anti-proliferative effect on different cancer cell lines, both in vitro and in vivo. RSV is also known to have modulatory effects on cell apoptosis, migration and growth via various signaling pathways. Though, RSV possesses great medicinal value, its applications as a therapeutic drug is limited. Problems like low oral bioavailability and poor aqueous solubility make RSV an unreliable candidate for therapeutic purposes. Additionally, the rapid gastrointestinal digestion of RSV is also a major barrier for its clinical translation. Hence, to overcome these disadvantages RSV-based nanodelivery systems have been considered in recent times. Nanodelivery systems of RSV have shown promising results in its uptake by the epithelial system as well as enhanced delivery to the target site. Herein we have tried to bring new new insights into the molecular mechanisms of DOX toxicity with respect to DNA damage, free radicals and whether RSV can be a playmaker as chemodulatory of DO x .

Obese mammary tumour-bearing mice are highly sensitive to doxorubicin-induced hepatotoxicity

“…Hepatotoxicity: Evaluation of apoptotic cell death and ALT DXR induces oxidative stress and is characterized by accumulation of reactive oxygen species (ROS), which decrease antioxidant defence systems, resulting in oxidative damage of DNA and apoptotic cell death (Song et al, 2019). It has been shown that oxidative stress is a major contributor of DXR-induced hepatotoxicity (Bengaied et al, 2017;Rashid et al, 2013). Obesity is associated with low grade chronic in ammation, excessive ROS production and oxidative stress.…”

“…It has been shown that DXR can induce hepatotoxicity, which limits its e cacy in anticancer therapy, resulting in poor patient prognosis and decreased overall survival of cancer patients (Bengaied et al, 2017;Song et al, 2019). DXR-induced oxidative stress is characterized by accumulation of reactive oxygen species (ROS), which decrease antioxidant defence systems, resulting in oxidative damage of deoxyribonucleic acid (DNA), therefore, mediating apoptotic cell death in hepatic tissue (Song et al, 2019).…”

Hepatoprotective Effects of L-Citrulline Against Doxorubicin-Induced Liver Damage in Rats: An Analysis of Serum Biomarkers

“…Further, ROS attacks inorganic phosphates, thus depleting hepatocytes of ATP and consequently triggering apoptosis. These events permit the escape of cytosolic enzymes, for example, ALT, AST, and GGT, from hepatocytes into the circulation, thereby increasing their serum levels [1,2,7,20].…”

“…Moreover, DOX use increased the risk of developing liver injury, for example, acute/subacute liver necrosis, toxic hepatitis, and hepatic coma, by 1.29× across all types of cancer [5,6]. Metabolism of DOX in hepatocytes generates an abundance of free radicals, and the resulting oxidative stress induces DNA damage, lipid peroxidation, disturbance of membrane integrity, and ATP depletion, all of which culminate in apoptosis [1,7]. Currently, toxicity prevention only comprises dosage optimization and antioxidant supplementation.…”

Obese mammary tumour-bearing mice are highly sensitive to doxorubicin-induced hepatotoxicity

“…DXR can also be detrimental to other organs, such as the liver, which plays an important physiological role in metabolism, glycogen and triglyceride storage, plasma protein synthesis and detoxification of toxic metabolites [ 8 ]. It has been shown that DXR can induce hepatotoxicity, which limits its efficacy in anticancer therapy, resulting in poor patient prognosis and decreased overall survival of cancer patients [ 9 , 10 ].…”