TY  - EJOU
AU  - Çekiç, Ç. Edip Güvenç
AU  - Filiz Başaran, F. Nesrin
AU  - İlhan Çelik, İ. Özgür
AU  - Şirin, Ş. Fevziye Burcu
AU  - Yilmaz, Y. Nigar
AU  - Soydan, S. Güray
TI  - The Effects of Nitric Oxide Synthase Inhibitors in Acetaminophen-Induced Hepatic Injury in Mice
T2  - Timisoara Medical Journal

PY  - 2022
VL  - 2022
IS  - 1
SN  - 1583-526X

AB  - (1) Aim of the Study: In this study, we aimed to evaluate the vascular damage and the effects of nitric oxide synthase (NOS) enzyme inhibitors in hepatic damage caused by high doses of acetaminophen (APAP). (2) Material and methods: Fifty-three Swiss albino male mice were used for this study. Hepatic and thoracic aorta toxicity caused by 2 or 6 h exposures to APAP (300 mg/kg intraperitoneally (i.p.)) were evaluated. The general NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME: 25 mg/kg and 50 mg/kg, i.p.) and the neuronal NOS inhibitor 7-nitroindazole (7-NI: 15 mg/kg, i.p.) were administered one hour before APAP exposure. (3) Results: Significant morphological deteriorations were observed after 6 h of APAP exposure in histopathological examinations of hepatic sections. Pre-treatment with L-NAME (at 50 mg/kg) or 7-NI before a 6 h APAP exposure significantly decreased hepatic toxicity (p < 0.05). Significant increases in ALT levels in 6 h of APAP exposure were decreased by both L-NAME (with the 25 mg/kg but not at 50 mg/kg) and 7-NI pre-treatments. No significant change was observed in the measured nitrate/nitrite levels and total antioxidant status in either serum or liver homogenates. No significant deteriorations were observed during either hematoxylin-eosin or immunohistochemical staining in thoracic aorta sections. In the thoracic artery sections, no statistical difference was found in acetylcholine-mediated relaxation, which may indicate endothelial dysfunction. (4) Conclusions: This study demonstrated that APAP-induced hepatic toxicity, especially neuronal NOS inhibitors, may decrease hepatic toxicity. It was also shown that APAP-induced hepatic toxicity was not accompanied by vascular dysfunction.
KW  - acetaminophen
KW  - hepatic toxicity
KW  - nitric oxide synthase inhibitor
KW  - 7-nitroindazole
DO  - 10.35995/tmj20220103