Hepatoprotective of Moringa oleifera seeds extract loading chitosan nanoparticles (MOS-CNPs) via induction of gene expression of NRF2 against CCl4-induced hepatic damage in male rats

Document Type : Research Paper

Authors

1 Veterinary Medicine Collage, Al-Qasim Green University, 51013 Babylon, Iraq.

2 Veterinary Medicine Collage, Al-Qasim Green University, 51013 Babylon, Iraq

Abstract

Objective
Liver diseases are a major health problem worldwide, and oxidative stress is involved in the pathogenesis of chemical-induced liver injury. Moringa oleifera (MO) seeds have potent antioxidant and hepatoprotective activities, which are, however, restricted by poor bioavailability. Chitosan nanoparticles (CNPs) are marketed as versatile delivery systems for bioactive compounds, offering improved pharmacokinetic profiles. The hepatoprotective and antioxidant potential of Moringa oleifera seeds ethanolic extract (MOSEE) loaded chitosan nanoparticles (CNPs) (MOS-CNPs) against carbon tetrachloride (CCl4)-induced hepatic injury in male rats.
Materials and methods
Forty male rats were randomly divided into five groups (n=8): Control (normal saline/olive oil), CCl4 only (negative control), CCl4 and MOS extract, CCl4 + MOS-CNPs Low dose and CCl4 + MOS-CNPs High dose. The experiment lasted 8 weeks. Biochemical markers of serum alanine aminotransferase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP) total protein, and total bilirubin were measured. The antioxidant status was estimated by total antioxidant capacity (T-AOC) and malondialdehyde (MDA) levels. Liver tissue histopathology was analyzed and gene expression of NRF2 determined by qRT-PCR.
Results
CCl4 treatment elevated serum ALT (217.95±9.87 U/L), AST (200.89±12.45 U/L), ALP (320.91±15.67 U/L) and TB (2.76±0.24 mg/dL) whilst decreased TP levels (4.15±0.28 g/dL) when compared to control groups(p<0,001). MOS-CNPs treatment dose-dependently reversed the above changes, and it had the best effect in high-dose group, such as ALT (77.96±5.12 U/L), AST (79.69±6.23 U/L), ALP (155.98±10.45 U/L), TB (0.99 ± 0.08 mg/dL) and TP (6.99 ± 0.32 g/dL). The activities of antioxidant markers in supplementation with MOS-CNPs 500 mg/kg markedly increased T-AOC (4.46±0.21 mmol/L) and lowered MDA (3.06±0.25 μmol/L) compared to the model group CCl4 (p<0.001). The expression of the NFR2 gene was markedly increased by MOS-CNPs treated groups in contrast to CCl4-intoxicated rats. Histopathological analysis confirmed the biochemical data showing decreased hepatocellular necrosis, inflammatory infiltration and fatty degenerescence.
Conclusion
MOS-CNPs have a better hepatoprotective and antioxidant effect as compared to free MOS extract by virtue of improved bioavailability and the controlled release pattern. The high-dose (500 mg/kg) provided the greatest protection against CCl4-induced liver damage by regulating oxidative stress and activation of the NRF2 antioxidant signaling pathway.

Keywords


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