Polydatin alleviates alcohol-induced acute liver injury in mice: Relevance of matrix metalloproteinases (MMPs) and hepatic antioxidants.
BACKGROUND
Alcohol, a most commonly consumed beverage, is the foremost cause of liver injury throughout the world. Polydatin, a stilbenoid glucoside, was known to possess antioxidant and anti-inflammatory properties and is being investigated for use in various disorders.


OBJECTIVE
The present study was intended at investigating the hepatoprotective efficacy of polydatin against acute-alcohol induced liver injury model in mice.


METHODS
C57BL/6 mice were fed with five doses of 50% ethyl alcohol (10ml/kg body weight) to induce acute liver injury. Effect of polydatin against alcohol induced hepatic injury was investigated by giving 50 or 100mg/kg polydatin, orally, for 8 days.


METHODS
Serum markers of liver injury, morphology, histology and fibrosis of liver tissue, levels of enzymatic and non-enzymatic antioxidants and the mitochondrial respiratory enzyme activities in liver tissue were investigated. The activities and the protein expression of matrix metalloproteinases (MMP-2 and -9), the expression of NF-κB in the liver tissue were also studied.


RESULTS
Polydatin pre-treatment significantly alleviated the alcohol induced hepatic injury by reducing the serum liver injury markers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), attenuating oxidative stress and restoring antioxidant balance in the hepatic tissue. Simultaneously, polydatin pre-treatment also prevented alcohol induced mitochondrial damage and refurbished the matrix metalloproteinases levels of the hepatic tissue.


CONCLUSIONS
The findings of the present study suggest that polydatin may have a potential benefit in preventing alcohol-induced acute hepatic injury.
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad-500 007, India.
Meghana
M
Koneru
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad-500 007, India.
Bidya Dhar
BD
Sahu
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad-500 007, India.
Sagarika
S
Gudem
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad-500 007, India.
Madhusudana
M
Kuncha
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad-500 007, India.
Halley Gora
HG
Ravuri
Animal House Facility, CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500 007, India.
Jerald Mahesh
JM
Kumar
Department of Pharmacology, A.U. College of Pharmaceutical Sciences, Andhra University, Visakhapatnam-530003, India.
Eswar Kumar
EK
Kilari
Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad-500 007, India. Electronic address: sistla@iict.res.in.
Ramakrishna
R
Sistla
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D045468:Fallopia japonica / Q000737:chemistry; D005960:Glucosides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy*; D008297:Male; D020782:Matrix Metalloproteinases / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D010936:Plant Extracts; D020782:Matrix Metalloproteinases
Acute alcohol-induced hepatic injury; CYP2E1; Matrix metalloproteinases; Nuclear factor-kappa B (NF-κB); Oxidative stress; Polydatin