Green Synthesized Zinc Oxide Nanoparticles as a Promising Adjuvant to Albendazole in the Management of Hydatid Cyst Disease: Molecular and Biochemical Insights.

BACKGROUND: This research focused on the green production and characterization of zinc oxide nanoparticles (ZNOP), as well as assessing their potential to manage hydatidosis infection in mice through affecting hydatid cysts, inflammatory factors, oxidative stress markers, apoptosis-related genes, as well as its hepatoprotective effects. METHODS: ZNOP was green synthesized using Ferula macrecolea extract. To induce experimental hydatidosis, mice were intraperitoneally inoculated with 1,500 viable Echinococcus granulosus protoscoleces. The experimental framework comprised eight distinct treatment groups, wherein infected mice received daily oral administrations of ZNOP at dosages of 5 or 10 mg/kg, albendazole (ALZ) at 100 and 200 mg/kg, or a combination of both agents. Treatment efficacy was determined by measuring cyst (number, size, and weight), the tissue levels of inflammatory markers [(interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B p65 (NF-κB p65)], apoptosis-related genes, oxidative stress, and liver functional enzymes. RESULTS: ZNOP had a spherical morphology and a compact surface structure with the average particle size was found to be 45 nm. The findings indicate that ZNOP treatment, particularly when combined with ALZ, significantly reduces cyst-related parameters such as count, size, and weight (p < 0.001). The group receiving ZNOP 5 mg/kg + ALZ 100 mg/kg exhibited IL-1β, TNF-α, and NF-κB p65 levels of 2.36, 3.64, and 1.43 pg/mL (p < 0.01), respectively. The combination of ZNOP 10 mg/kg with ALZ 100 mg/kg further improved the results, with values of 1.93, 3.29, and 0.912 pg/mL (p < 0.01), which were nearly comparable to the non-infected control. The most impressive outcomes (P < 0.001) were observed in the combination therapy groups (ALZ 100 mg/kg + ZNOP 5 and 10 mg/kg), where MDA and NO levels were significantly reduced and nearly matched those of the non-infected group. The combination of 5 mg/kg ZNOP and 100 mg/kg ALZ led to a 3.71-fold increase in Caspase-3 (p < 0.001), 3.43-fold in BAX (p < 0.001), and a 2.59-fold decrease in BCL-2 (p < 0.001). In the group receiving 10 mg/kg ZNOP + 100 mg/kg ALZ, the fold changes were even more pronounced: 4.35-fold for Caspase-3 (p < 0.001), 3.79-fold for BAX (p < 0.001), and a 2.77-fold reduction in BCL-2 (p < 0.001). The administration of ZNOP mainly the combination of ZNOP (5 and 10 mg/kg) with ALZ (100 mg/kg) yielded the most favorable results and moderated the level of liver enzymes, provided liver protection (p < 0.001). CONCLUSION: The study showed that ZNOP, especially with ALZ, effectively reduced hydatid cysts in terms of number, size, and mass. It also lowered inflammation and oxidative stress, showing strong anti-inflammatory and antioxidant effects. At the molecular level, ZNOP boosted apoptosis-related genes, suggesting it can help stop cyst growth. Importantly, ZNOP is non-toxic and protects liver tissue, making it a good adjuvant to reduce side effects of traditional drugs.