Fukaya Shiori, Yoshioka Hiroki, Okano Tadahiro, Nagatsu Akito, Miura Nobuhiko, Nonogaki Tsunemasa, Onosaka Satomi
Department of Pharmacy, College of Pharmacy, Kinjo Gakuin University.
Faculty of Nutrition, Kobe Gakuin University.
Biol Pharm Bull. 2017;40(9):1590-1594. doi: 10.1248/bpb.b17-00344.
A wide range of medications are routinely used to maintain and improve human health. Hence, it is essential that we understand and predict adverse effects caused by the combined use of multiple medications. In the present study, we investigated whether the combination of carbon tetrachloride (CCl) and acetaminophen (APAP) had a detrimental effect on the liver. Mice injected with APAP (100 mg/kg) showed no significant changes in hepatic injury markers (alanine aminotransferase and aspartate aminotransferase), histopathological findings, pro-inflammatory cytokine levels, or hepatic oxidative stress. In contrast, a single injection of CCl (15 mg/kg) led to a significant increase in hepatic injury, in addition to an increase in pro-inflammatory cytokine levels and oxidative stress. Co-administration of APAP and CCl resulted in exacerbation of these hepatic injuries. Our results suggest that a non-toxic dose of APAP has the potential to increase CCl-induced liver damage and oxidative stress.
广泛的药物被常规用于维持和改善人类健康。因此，我们理解和预测多种药物联合使用所引起的不良反应至关重要。在本研究中，我们调查了四氯化碳（CCl）和对乙酰氨基酚（APAP）的联合使用是否对肝脏有有害影响。注射APAP（100毫克/千克）的小鼠在肝损伤标志物（丙氨酸转氨酶和天冬氨酸转氨酶）、组织病理学结果、促炎细胞因子水平或肝脏氧化应激方面没有显著变化。相比之下，单次注射CCl（15毫克/千克）除了导致促炎细胞因子水平和氧化应激增加外，还导致肝损伤显著增加。APAP和CCl共同给药导致这些肝损伤加剧。我们的结果表明，无毒剂量的APAP有可能增加CCl诱导的肝损伤和氧化应激。
