Holothuria arenicola Extract-Loaded Polycaprolactone Nanocapsules Attenuate Bile Duct Ligation-Induced Acute Liver Injury

Introduction: Cholestatic liver diseases are characterized by jaundice and cholestasis with various consequences that can lead to end-stage liver disease. The present study aims to as-sess the protective effect of the Holothuria Arenicola extract (HaE)-loaded polycaprolactone (PCL) nanocapsule in a model of bile duct ligation (BDL) in male albino rats. Methods: Thirty male albino rats were divided into two groups: bile duct ligated (BDL) (24 rats) and sham-operated control (6 rats/group). BDL was then divided into 4 subgroups: model un-treated, HaE-treated (200 mg/kg, orally), PCL (100 mg/kg, orally), and HaE-PCL (100 mg/kg, orally). Each treatment is conducted for 14 days after BDL surgery. Results: The HaE-PCL nanocapsule exhibited a diameter of 196 nm, a zeta potential of 19.7, and a polydispersity index of 0.7. Treatment with HaE-PCL markedly diminished levels of alanine aminotransferase (23.52 ± 0.83), aspartate aminotransferase (53.62 ± 1.24), alkaline phosphatase (2055.31 ± 17.19), gamma-glutamyl transferase (3.15 ± 0.64), globulins (7.24 ± 0.10), total pro-tein (3.33 ± 0.15), bilirubin (3.46 ± 0.46), creatinine (0.65 ± 0.02), urea (13.36 ± 0.28), uric acid (1.13 ± 0.07), malondialdehyde (liver 1.06 ± 0.09, kidney 1.18 ± 0.08), and nitric oxide (liver 180.5 ± 9.42, kidney 456.02 ± 19.6), while simultaneously increasing levels of glutathione re-duced (liver 2.07 ± 0.17, kidney 2.07 ± 0.17) and catalase (liver 354.82 ± 11.4, kidney 227.76 ± 3.15). Histopathological analysis of HaE-PCL-treated rats demonstrated substantial enhancements in liver and kidney morphology, along with a marked reduction in collagen deposition. Further-more, the immunohistochemistry study demonstrated a significant reduction in TNF-α expression in rats administered HaE-PCL. Discussion: These findings demonstrated that HaE-PCL effectively protects the liver and kidney from cholestasis-induced damage by improving biochemical characteristics and inhibiting oxida-tive stress and inflammation. Conclusion: HaE-PCL exhibits anticholestatic action due to its antioxidant, anti-inflammatory, and antifibrotic properties.