Hepatorenal protective and antitumor effects of astaxanthin-loaded chitosan nanoparticles against ehrlich ascites carcinoma in mice through antioxidant, anti-inflammatory, and apoptotic pathway modulation

Ehrlich ascites carcinoma (EAC) is an aggressive experimental tumor model associated with severe oxidative stress, inflammation, and hepatorenal injury. Astaxanthin (ASX), a potent natural antioxidant carotenoid, has demonstrated anticancer and cytoprotective properties; however, its therapeutic application is limited by poor bioavailability and stability. Therefore, this study investigated the anticancer and hepatorenal protective effects of astaxanthin-loaded chitosan nanoparticles (ASX-CNPs) compared with free ASX in EAC-bearing mice. Ninety female Swiss albino mice were randomly allocated into six groups: control, ASX, ASX-CNPs, EAC, EAC + ASX, and EAC + ASX-CNPs. Tumor progression, survival rate, oxidative stress biomarkers, inflammatory mediators, apoptotic markers, and histopathological alterations in hepatic and renal tissues were evaluated. Antioxidant parameters included SOD, CAT, GPx, GSH, TAC, and TBARS. Inflammatory and apoptotic signaling pathways were assessed through measurement of COX-2, TNF-α, IFN-γ, IL-1β, Bcl-2, Bax, and caspase-3 expression levels. ASX-CNPs markedly suppressed tumor progression and improved survival compared with free ASX. Treatment with ASX-CNPs significantly downregulated Bcl-2 expression while upregulating Bax and caspase-3, indicating enhanced apoptotic activity. Antioxidant defenses were significantly restored, as evidenced by increased SOD, CAT, GPx, GSH, and TAC levels, alongside reduced TBARS. Inflammatory responses were attenuated through decreased COX-2 activity and reduced TNF-α, IFN-γ, and IL-1β levels. Histopathological examination confirmed substantial protection against EAC-induced hepatic and renal damage. Overall, ASX-CNPs demonstrated greater therapeutic efficacy than free ASX across biochemical, molecular, and histopathological assessments. ASX-loaded chitosan nanoparticles exerted potent anticancer, antioxidant, anti-inflammatory, and hepatorenal protective effects in EAC-bearing mice. The enhanced efficacy of ASX-CNPs relative to free ASX is likely attributable to improved bioavailability and targeted modulation of oxidative stress, inflammatory, and apoptotic pathways, supporting their potential as a promising nanotherapeutic strategy for cancer-associated organ injury. Astaxanthin-loaded chitosan nanoparticles (ASX-CNPs) were developed to enhance the efficacy of astaxanthin against Ehrlich ascites carcinoma (EAC). Treatment with ASX-CNPs significantly reduced tumor growth and enhanced liver and kidney function compared to free ASX. The nanoformulation elevated pro-apoptotic marker levels (Bax, Caspase-3) and reduced oxidative stress (normalizing GSH and TAC levels) and inflammation (decreasing COX-2, TNF-α, IFN-γ, and IL-1β levels). ASX-CNPs demonstrate significant anticancer and hepatorenal protective effects through the regulation of apoptotic, oxidative, and inflammatory signaling pathways.