Protective effect of a phytocompound on oxidative stress and DNA fragmentation against paracetamol-induced liver damage.
The hepatoprotective potential DTS (1.5 g/kg bw, Denshici-to-Chiusei, Kyotsu Jigyo, Tokyo, Japan) was evaluated against either toxic (1.5 g/kg bw) and sub-toxic (150 mg/kg bw) dosage of paracetamol-induced liver injury in Sprague-Dawley rat. Paracetamol intoxication caused a reduction of serum total protein and increase levels of serum alkaline phosphatase (ALP), aspartate aminotranferase (AST) and serum alanine aminotranferase (ALT) at higher extent in the toxic group. This phenomenon was paralleled by an impaired liver redox status (reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) and increased MDA in both paracetamol-administered groups. Moreover, a marked reduction of ATPase and thiols together with DNA fragmentation occurred in liver tissue. Animals pretreated with DTS showed a marked mitigation of the severity of liver enzyme and of the impaired redox status of the liver. Moreover, DTS partly prevented the DNA fragmentation and the decline of liver tissue ATPase and protein thiol assay as compared with both groups treated with paracetamol alone. Although more detailed studies are awaited to ascertain the detailed mode of action of DTS, it wouls seem to be related to the prevention of formation of the reactive oxygen groups thereby preventing the damage on the hepatocytes and possibly modulating the genes responsible for synthesis of liver antioxidant enzymes thus providing marked DNA protection.<br />
Marotta
Francesco
F
University of Milan,Via Pisanello, 4 20146 Milano, Italy. fmarchimede@libero.it
Yadav
Hariom
H
Gumaste
Upendra
U
Helmy
Amr
A
Jain
Shalini
S
Minelli
Emilio
E
D000082:Acetaminophen; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D019610:Cytoprotection; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000975:Antioxidants; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D013438:Sulfhydryl Compounds; D000082:Acetaminophen; D000251:Adenosine Triphosphatases