Naringenin Regulates Doxorubicin-Induced Liver Dysfunction: Impact on Oxidative Stress and Inflammation

Abstract

Doxorubicin (Dox) is an operational and largely used anticancer drug, used to treat an array of malignancies. Nonetheless, its beneficial use is constrained due to its renal and hepatotoxicity dose dependently. Numerous research findings favor the use of antioxidants may impact Dox-induced liver injury/damage. In the current study, Wistar rats were given naringenin (50 and 100 mg/kg b.wt.) orally for 20 days as prophylactic dose, against the hepatotoxicity induced by single intraperitoneal injection of Dox (20 mg/kg b.wt.). Potency of naringenin against the liver damage caused by Dox was assessed by measuring malonyl aldehyde (MDA) as a by-product of lipid peroxidation, biochemical estimation of antioxidant enzyme system, reactive oxygen species (ROS) level, and inflammatory mediators. Naringenin-attenuated ROS production, ROS-induced lipid peroxidation, and replenished reduced antioxidant armory, namely, catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH). Naringenin similarly diminished expression of Cox-2 and levels of NF-κB and other inflammatory molecules induced by the Dox treatment. Histology added further evidence to the defensive effects of naringenin on Dox-induced liver damage. The outcomes of the current study reveal that oxidative stress and inflammation are meticulously linked with Dox-triggered damage, and naringenin illustrates the potential effect on Dox-induced hepatotoxicity probably through diminishing the oxidative stress and inflammation.

Pterocarpus mildbraedii(Harms) extract resolves propanil‐induced hepatic injury via repression of inflammatory stress responses in Wistar rats

“…For instance, the administration of flavonoid-rich extract of orange juice diminished iNOS in the colon of dinitrobenzene sulfonic acid-treated mice (Fusco et al, 2017). Wali, Rashid, et al (2020) reported that naringenin, at the doses of 50 and 100 mg/kg, decreased the expressions of COX-2 in experimental hepatic inflammation triggered by doxorubicin.…”

“…Suppression of NF-κB and COX-2 expressions could block the activation of downstream cytokines, and thus, afford protection against propanil-induced hepatotoxicity (Wali, Rashid, et al, 2020).…”

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

“…In alleviation of DOX toxicity, phytochemicals reduce levels of proinflammatory cytokines via downregulating NF-κB signaling pathway [ 97 ]. Furthermore, apoptotic proteins such as Bax and caspase-3 undergo downregulation, while antiapoptotic factor Bcl-2 demonstrates an increase in expression to ameliorate DOX side effects [ 98 ].…”

Plant-Derived Chemicals: A Source of Inspiration for New Drugs

“…Naringenin was found to decrease lipid peroxidation by diminishing membrane fluidity and lowering the production of ROS, increase anti-oxidant enzymes, and decrease the levels of inflammatory mediators. A further histological investigation on liver tissues confirmed the preventative effect of naringenin against doxorubicin-induced hepatotoxicity [ 4 ].…”