title: Antioxidant effects of pineapple vinegar in reversing of paracetamol-induced liver damage in mice.
abstract: BACKGROUND
  Pineapple (Ananas comosus) was demonstrated to be hepatoprotective. This study aims to investigate the reversing effects of pineapple vinegar on paracetamol-induced liver damage in murine model.
  
  
  METHODS
  Pineapple juice was fermented via anaerobic and aerobic fermentation to produce pineapple vinegar. Male BALB/c mice (n = 70) were separated into 7 treatment groups (n = 10). Pineapple vinegar (0.08 and 2 mL/kg BW) and synthetic vinegar were used to treat paracetamol-induced liver damage in mice. The hepatoprotective effects were determined by serum biochemistry profiles (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and triglyceride (TG)), liver antioxidant levels (ferric-reducing ability plasma (FRAP), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione assays (GSH)) and histopathological examination with hematoxylin and eosin (H&E) staining. The effects were further evaluated by the expression levels of iNOS, NF-κB, and cytochrome P450 2E1 by quantitative real-time PCR and Western blot analyses. Vinegar samples were also tested for in vitro antioxidant (FRAP, 2,2-diphenyl-2-picrylhydrazyl (DPPH), and total phenolic content (TPC)). Soluble phenolic acid contents in the samples were identified by HPLC.
  
  
  RESULTS
  Pineapple vinegar contained 169.67 ± 0.05 μg GAE/mL of TPC, with 862.61 ± 4.38 μg/mL gallic acid as the main component. Oral administration of pineapple vinegar at 2 mL/kg BW reduced serum enzyme biomarker levels, including AST (P = 0.008), ALT (P = 0.006), ALP (P = 0.002), and TG (P = 0.006) after 7 days of paracetamol treatment. Liver antioxidant levels such as hepatic glutathione (P = 0.003), SOD (P < 0.001), lipid peroxidation (P = 0.002) and FRAP (P <0.001) were restored after the treatment. Pineapple vinegar reduced the expressions of iNOS (P = 0.003) and NF-kB (P = 0.003) and the level of NO (P = 0.003) significantly. Pineapple vinegar also downregulated liver cytochrome P450 protein expression.
  
  
  CONCLUSIONS
  Oral administration of pineapple vinegar at 0.08 and 2 mL/kg BW reduced serum enzyme biomarker levels, restored liver antioxidant levels, reduced inflammatory factor expressions, and down regulated liver cytochrome P450 protein expression in paracetamol-induced liver damage in mice.
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, Serdang, Selangor 43400 Malaysia.
authors.forename: Nurul Elyani
authors.initials: NE
authors.lastname: Mohamad
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor 43400 Malaysia.
authors.forename: Swee Keong
authors.initials: SK
authors.lastname: Yeap
authors.affiliation: Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Sungai Long Campus, Jalan Sungai Long, Bandar Sungai Long, Cheras, Kajang, 43000 Selangor Malaysia.
authors.forename: Kian Lam
authors.initials: KL
authors.lastname: Lim
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, Serdang, Selangor 43400 Malaysia.
authors.forename: Hamidah Mohd
authors.initials: HM
authors.lastname: Yusof
authors.affiliation: Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Sungai Long Campus, Jalan Sungai Long, Bandar Sungai Long, Cheras, Kajang, 43000 Selangor Malaysia.
authors.forename: Boon Kee
authors.initials: BK
authors.lastname: Beh
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor 43400 Malaysia.
authors.forename: Sheau Wei
authors.initials: SW
authors.lastname: Tan
authors.affiliation: School of Biomedical Sciences, The University of Nottingham Malaysia Campus, Jalan Broga, 43500, Semenyih, Selangor 43400 Malaysia.
authors.forename: Wan Yong
authors.initials: WY
authors.lastname: Ho
authors.affiliation: Biotechnology Research Centre, Malaysian Agricultural Research and Development Institute (MARDI), Serdang, Selangor 43400 Malaysia.
authors.forename: Shaiful Adzni
authors.initials: SA
authors.lastname: Sharifuddin
authors.affiliation: Biotechnology Research Centre, Malaysian Agricultural Research and Development Institute (MARDI), Serdang, Selangor 43400 Malaysia.
authors.forename: Anisah
authors.initials: A
authors.lastname: Jamaluddin
authors.affiliation: Biotechnology Research Centre, Malaysian Agricultural Research and Development Institute (MARDI), Serdang, Selangor 43400 Malaysia.
authors.forename: Kamariah
authors.initials: K
authors.lastname: Long
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, Serdang, Selangor 43400 Malaysia.
authors.forename: Nik Mohd Afizan
authors.initials: NM
authors.lastname: Nik Abd Rahman
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, Serdang, Selangor 43400 Malaysia.
authors.forename: Noorjahan Banu
authors.initials: NB
authors.lastname: Alitheen