Antioxidant and Anti‑caspase‑3 Activity of Chitosan‑Pinus merkusii Extract Nanoparticle on Lead Acetate‑induced Hepatotoxicity

Objective: In the present study, we investigated the impact of Chitosan‑P. merkusii extract nanoparticle against lead acetate‑induced hepatotoxicity in rats. Materials and Methods: Chitosan‑P. merkusii extract nanoparticle was characterized by dynamic light scattering (DLS) and scanning electron microscope (SEM). The fifty male rats were divided into control group (rats were given daily with distilled water), lead acetate group (rats were injected with lead acetate [15 mg/Kg BW i. p] for the 7 consecutive days), and the treatment group (rats were given the Chitosan‑P. merkusii extract nanoparticle [100 mg, 200 mg, and 400 mg/Kg BW orally] once in a day for 11 days and on the 4th day, they were injected with lead acetate [15 mg/Kg BW i. p] for 7 days). On day 11, the rats’ blood samples were taken by a cardiac puncture to measure the levels of serum glutamic‑oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and alkaline phosphatase (ALP). Furthermore, rats were sacrificed, and liver tissues were collected to evaluate the malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx). The liver tissues also were subjected to histological evaluations and immunohistochemical evaluations of the expressions of caspase‑3. Results: The results showed that DLS showed the formation of Chitosan‑P. merkusii extract nanoparticle with the size of 530.2 ± 30.27 nm. SEM images of the Chitosan‑P. merkusii extract nanoparticles showed an irregular shape, and the morphology surface showed the rough surface. Injection of lead acetate (15 mg/Kg BW) for 7 days resulted in a significant (P < 0.05) increase in SGOT, SGPT, ALP, MDA level, and caspase‑3 expression. Lead acetate also significantly (P < 0.05) decreased in SOD and GPx. Treatment with the Chitosan‑P. merkusii extract nanoparticle (400 mg/Kg BW) significantly (P < 0.05) decreased the elevated SGPT, SGOT, ALP, MDA levels, and caspase‑3 expressions as compared to lead acetate group. Treatment with Chitosan‑P. merkusii extract nanoparticle (400 mg/Kg BW) also resulted in a significant (P < 0.05) increase in SOD and GPx, as compared to lead acetate group. Administration of lead acetate to rats can cause histopathological changes such as loss of the normal structure of hepatic cells, blood congestion, and necrosis whereas rats treated with Chitosan‑P. merkusii extract nanoparticle showed an improvement in these changes, and the tissue appears with normal structures. Conclusion: This study indicates that Chitosan‑P. merkusii nanoparticle could be a potent natural product that provides a promising hepatoprotective effect against lead acetate‑induced hepatotoxicity in rats, through increasing antioxidant and inhibiting caspase‑3 expression.