title: Biochemically and histopathologically comparative review of thiamine's and thiamine pyrophosphate's oxidative stress effects generated with methotrexate in rat liver.
abstract: BACKGROUND
  Oxidative liver injury occurring with methotrexate restricts its use in the desired dose. Therefore, whether or not thiamine and thiamine pyrophosphate, whose antioxidant activity is known, have protective effects on oxidative liver injury generated with methotrexate was comparatively researched in rats using biochemical and histopathological approaches.
  
  
  METHODS
  Thiamine pyrophosphate+methotrexate, thiamine+methotrexate, and methotrexate were injected intraperitoneally in rats for 7 days. After this period, all animals' livers were excised, killing them with high-dose anesthesia, and histopathologic and biochemical investigations were made.
  
  
  RESULTS
  Biochemical results demonstrated a significant elevation in level of oxidant parameters such as MDA and MPO, and a reduction in antioxidant parameters such as GSH and SOD in the liver tissue of the methotrexate group. Also, the quantity of 8-OHdG/dG, a DNA injury product, was higher in the methotrexate group with high oxidant levels and low antioxidant levels, and the quantity of 8-OHdG/dG was in the thiamine pyrophosphate group with low oxidant levels and high antioxidant levels. In the thiamine and control groups, the 8-OHdG/dG rate was 1.48 ± 0.35 pmol/L (P>0.05) and 0.55 ± 0.1 pmol/L (P<0.0001). Thiamine pyrophosphate significantly decreased blood AST, ALT and LDH, but methotrexate and thiamine did not decrease the blood levels of AST, ALT and LDH. Histopathologically, although centrilobular necrosis, apoptotic bodies and inflammation were monitored in the methotrexate group, the findings in the thiamine pyrophosphate group were almost the same as in the control group.
  
  
  CONCLUSIONS
  Thiamine pyrophosphate was found to be effective in methotrexate hepatotoxicity, but thiamine was ineffective.
authors.affiliation: Ibni Sina Hospital, Department of General Surgery, Kayseri, Turkey.
authors.forename: Ismail
authors.initials: I
authors.lastname: Demiryilmaz
authors.forename: Ebru
authors.initials: E
authors.lastname: Sener
authors.forename: Nihal
authors.initials: N
authors.lastname: Cetin
authors.forename: Durdu
authors.initials: D
authors.lastname: Altuner
authors.forename: Bahadir
authors.initials: B
authors.lastname: Suleyman
authors.forename: Fatih
authors.initials: F
authors.lastname: Albayrak
authors.forename: Fatih
authors.initials: F
authors.lastname: Akcay
authors.forename: Halis
authors.initials: H
authors.lastname: Suleyman
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008727:Methotrexate / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013831:Thiamine / Q000494:pharmacology*; D013835:Thiamine Pyrophosphate / Q000494:pharmacology*
chemical_list: D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003849:Deoxyguanosine; D005978:Glutathione; D013835:Thiamine Pyrophosphate; D013831:Thiamine; D008727:Methotrexate