title: Biochemical and Histological Effects of Thiamine Pyrophosphate against Acetaminophen-Induced Hepatotoxicity.
abstract: The aim of this study was to investigate whether thiamine pyrophosphate (TPP) has biochemical and histological preventive effects on oxidative liver damage induced by paracetamol (APAP). Rats were divided into the following groups: healthy control (HG), APAP (AG, 1500 mg/kg, orally), thiamine pyrophosphate (TPPG, 100 mg/kg, intraperitoneally), APAP+NAC (ANAC, 100 mg/kg, intraperitoneally), APAP+TPP (ATPG) and APAP+NAC+TPP (ANTG). Oxidant, antioxidant parameters, liver function tests and histological assessment were performed between groups. Malondialdehyde levels in the AG, HG, TPPG, ANAC, ATPG and ANTG groups were 0.470 ± 0.210, 0.213 ± 0.004, 0.194 ± 0.001, 0.197 ± 0.06, 0.199 ± 0.008 and 0.173 ± 0.010 μmol/g protein, respectively. Total glutathione levels were 7.787 ± 0.395, 14.925 ± 0.932, 13.200 ± 0.984, 13.162 ± 0.486, 13.287 ± 0.787 and 13.500 ± 0.891 μm/g protein, respectively. In the AG group, marked liver damage occurred with the elevation of liver function tests and oxidative stress markers, such as malondialdehyde, myeloperoxidase and nitric oxide (p < 0.05). Biochemical results were congruent with the histological changes of oxidative damage. Compared to the AG group (p < 0.05), TPP significantly reduced oxidant parameter levels in the ATPG group and simultaneously increased the antioxidant parameter levels of catalase and glutathione. The histological changes were improved to almost normal hepatic structure. Moreover, TPP had nearly the same hepatoprotective effect as NAC, and there was statistically no additional benefit with NAC co-treatment. There was no statistically significant difference (p > 0.05) among the ANAC, ANTG and ATPG groups in terms of oxidant/antioxidant levels. TPP proved to be as efficacious as standard therapy and may be beneficial in APAP-induced hepatotoxicity.
authors.affiliation: Department of Internal Medicine, Adnan Menderes University School of Medicine, Aydin, Turkey.
authors.forename: Hilal Bektas
authors.initials: HB
authors.lastname: Uysal
authors.affiliation: Department of Emergency, Adnan Menderes University School of Medicine, Aydin, Turkey.
authors.forename: Bekir
authors.initials: B
authors.lastname: Dağlı
authors.affiliation: Department of Biochemistry, Adnan Menderes University School of Medicine, Aydin, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Yılmaz
authors.affiliation: Department of Histology, Adnan Menderes University School of Medicine, Aydin, Turkey.
authors.forename: Fadime
authors.initials: F
authors.lastname: Kahyaoğlu
authors.affiliation: Department of Histology, Adnan Menderes University School of Medicine, Aydin, Turkey.
authors.forename: Alparslan
authors.initials: A
authors.lastname: Gökçimen
authors.affiliation: Department of Biostatistics, Adnan Menderes University School of Medicine, Aydin, Turkey.
authors.forename: İmran Kurt
authors.initials: İK
authors.lastname: Ömürlü
authors.affiliation: Department of Medical Pharmacology, Adnan Menderes University School of Medicine, Aydin, Turkey.
authors.forename: Buket
authors.initials: B
authors.lastname: Demirci
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D017208:Rats, Wistar; D013835:Thiamine Pyrophosphate / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D009569:Nitric Oxide; D000082:Acetaminophen; D008315:Malondialdehyde; D002374:Catalase; D009195:Peroxidase; D005978:Glutathione; D013835:Thiamine Pyrophosphate; D000111:Acetylcysteine