Protective Role of 2,3-Dichloro-6-(Trifluoromethoxy)Quinoxaline against DOX-induced Liver Inflammation
Mohannad A Alkasih, Noha Juma, Hatoon Niyazi, Noora Daafa, Bandar Hasan Saleh, Muna Alqarni, Ala Azhari, Wafaa Alhazmi, Khalil Alkuwaity, Ohood Alharbi, Rawan Altalhi, Mohammed K. Alghamdi, Mohammed Alsieni, Samah Labban, Riyadh Almalki, Sultan Ahmed Foad Samman, Turki M. Alharthi, Ahmad M. Alzahrani, Ahmad Jamal, Karem Ibrahem, Abdelbagi AlfadilBackground
Doxorubicin (DOX) is a powerful anthracycline anti-neoplastic agent, and its therapeutic application is frequently restricted because of its liver-damaging effects. In this study, we found that DOX induces acute liver toxicity in rats, and the mechanisms underlying these effects were investigated.
Purpose
This study aimed to assess the hepatoprotective effects of 2,3-dichloro-6-(trifluoromethoxy) quinoxaline (DTQ) against DOX-induced acute liver toxicity in rats and to investigate the underlying mechanisms involved.
Materials and Methods
Male Wistar rats were administered an intraperitoneal dose of DOX on days 12–14 of the experiment to induce acute liver toxicity. The rats received DTQ (30 and 60 mg/kg, orally) continuously from day 1 for 14 days, along with DOX on days 12–14. Different biochemical parameters (liver function enzymes, lipid peroxidation, and oxidative stress) were measured.
Results
DOX treatment increased the levels of liver function enzymes, lipid peroxidation, and oxidative stress by suppressing the production of antioxidant enzymes. Additionally, DOX treatment triggered the expression of pro-inflammatory cytokines and inflammatory mediators in the liver. Histological analysis further confirmed the structural liver damage resulting from DOX treatment.
Conclusion
DTQ administration offered protection against the harmful effects of DOX on the liver, as indicated by the normalization of altered biochemical parameters and reduction in oxidative stress and inflammation. The results of this study indicate that DTQ exerts liver-protective effects against DOX-induced acute liver toxicity, likely due to its strong antioxidant and anti-inflammatory properties, which modulate the cellular signaling pathways.