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Published on: October 13, 2018
Nanoparticles from grape seed extract inhibit inflammatory cytokines and ameliorate CCl4-induced hepatotoxicity
Neveen Adel Madbouly1, Doaa Mohammad Ali2, Alyaa Ahmed Farid3
1Zoology Department, Faculty of Science, Cairo University, Giza, 12613, Egypt. n.madbouly@cu.edu.eg.
Background:
Xenobiotic-induced liver injury is a clinically reverent condition which may influence the development of steatohepatitis via affecting numerous pathways such as oxidative stress, inflammation, mitochondorial functioning and fatty acid biosynthesis. The current study was conducted to survey the antioxidant effect of grape seeds extract nanoparticles (GS extract NPs) against CCl4-induced oxidative stress, hepatic dysfunction and inflammatory changes.
Methods:
Hydroethanolic Grape seed (GS) extract was prepared and characterized using high performance liquid chromatography (HPLC), inductively coupled plasma-mass spectrometry (ICP-MS) and gas chromatography-mass spectrometry (GC-MS). Then, GS extract NPs were synthesized and in vitro antioxidant, anticoagulant, cytotoxicity and anti-inflammatory testes confirmed biological activity. Finally, Twenty-five male Sprague-Dawley rats were divided into five groups (n = 5/group). Either GS extract (200 mg/kg/day) or GS extract NPs (100 mg/kg/day) were orally administrated independently to CCL4-intoxicated (0.5 ml/kg twice a week for 3 weeks) rats. Four weeks after the treatment, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) were monitored. In addition, hepatic Malondialdehyde (MDA), Superoxide dismutases (SOD), Glutathione (GSH) and catalase (CAT) and hepatic inflammatory cytokines were assessed.
Results:
GS extract NPs were spherical-shaped and regular particles (size: 16.5 to 22.5 nm and zeta potential: -39.42 mv). CCL4 -intoxicated rats showed increase of serum ALT, AST, ALP, elevation in MDA level accompanied by a decline in SOD, GSH and CAT levels in liver, compared with CCL4-untreated rats. Immunologically, serum C-Reactive Protein (CRP) and hepatic interleukin 1β (IL-1β), IL-4, IL-6 and Tumor Necrosis Factor-alpha (TNF-α) showed significant elevation, compared with CCL4 -untreated rats. Conversely, GS extract NPs supplementation potentially ameliorate hepatic functions by normalization of serum ALT, AST and ALP, reduced MDA level, improved antioxidant CAT, regulated liver inflammatory cytokines via maximal reduction of hepatic IL-1β, IL-4, IL-6 and TNF-α.
Conclusion:
GS extract NPs augmented the antioxidant and anti-inflammatory properties of GS extract thereby protecting the liver against oxidative stress induced by CCl4 as hepatic xenobiotic.
Clinical Trial Number:
Not applicable.
Insights
Grape seed extract nanoparticles (GS extract NPs) effectively protected the liver from oxidative stress and inflammation caused by carbon tetrachloride (CCl4). GS extract NPs demonstrated significant antioxidant and anti-inflammatory properties, improving liver function in rats.
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Xenobiotic-induced liver injury is a significant health concern.
- It can lead to steatohepatitis by affecting oxidative stress, inflammation, mitochondrial function, and fatty acid biosynthesis.
- Grape seed extract nanoparticles (GS extract NPs) were investigated for their protective effects.
Purpose of the Study:
- To evaluate the antioxidant effects of GS extract NPs against CCl4-induced oxidative stress.
- To assess the impact of GS extract NPs on hepatic dysfunction and inflammatory changes.
- To compare the efficacy of GS extract NPs with the original grape seed extract.
Main Methods:
- Grape seed (GS) extract was prepared and characterized using HPLC, ICP-MS, and GC-MS.
- GS extract NPs were synthesized and tested for in vitro antioxidant, anticoagulant, cytotoxicity, and anti-inflammatory activities.
- Male Sprague-Dawley rats were intoxicated with CCl4 and treated with GS extract or GS extract NPs, followed by biochemical and histological analyses.
Main Results:
- CCl4 intoxication increased serum ALT, AST, ALP, and MDA levels, while decreasing SOD, GSH, and CAT levels.
- Inflammatory markers (CRP, IL-1β, IL-4, IL-6, TNF-α) were significantly elevated in CCl4-intoxicated rats.
- GS extract NPs treatment normalized liver enzymes, reduced MDA, improved antioxidant levels, and significantly decreased inflammatory cytokines.
Conclusions:
- GS extract NPs possess enhanced antioxidant and anti-inflammatory properties compared to the original extract.
- These nanoparticles effectively protect the liver against CCl4-induced xenobiotic injury.
- GS extract NPs represent a promising therapeutic agent for managing drug-induced liver injury.
