Kawakami Kayoko, Moritani Chie, Uraji Misugi, Fujita Akiko, Kawakami Koji, Hatanaka Tadashi, Suzaki Etsuko, Tsuboi Seiji
School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Naka-Ku, Okayama 703-8516, Japan.
Okayama Prefectural Technology Canter for Agriculture, Forestry and Fisheries, Research Institute for Biological Sciences (RIBS), Okayama, 7549-1 Kibichuo-cho, Kaga-gun, Okayama 716-1241, Japan.
J Clin Biochem Nutr. 2017 Mar;60(2):115-120. doi: 10.3164/jcbn.16-44. Epub 2016 Dec 6.
Glutathione, the most abundant intracellular antioxidant, protects cells against reactive oxygen species induced oxidative stress and regulates intracellular redox status. We found that rice peptides increased intracellular glutathione levels in human hepatoblastoma HepG2 cells. Acetaminophen is a commonly used analgesic. However, an overdose of acetaminophen causes severe hepatotoxicity via depletion of hepatic glutathione. Here, we investigated the protective effects of rice peptides on acetaminophen-induced hepatotoxicity in mice. ICR mice were orally administered rice peptides (0, 100 or 500 mg/kg) for seven days, followed by the induction of hepatotoxicity via intraperitoneal injection of acetaminophen (700 mg/kg). Pretreatment with rice peptides significantly prevented increases in serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels and protected against hepatic glutathione depletion. The expression of γ-glutamylcysteine synthetase, a key regulatory enzyme in the synthesis of glutathione, was decreased by treatment with acetaminophen, albeit rice peptides treatment recovered its expression compared to that achieved treatment with acetaminophen. In addition, histopathological evaluation of the livers also revealed that rice peptides prevented acetaminophen-induced centrilobular necrosis. These results suggest that rice peptides increased intracellular glutathione levels and could protect against acetaminophen-induced hepatotoxicity in mice.
谷胱甘肽是细胞内最丰富的抗氧化剂，可保护细胞免受活性氧诱导的氧化应激，并调节细胞内氧化还原状态。我们发现大米肽可提高人肝癌HepG2细胞内的谷胱甘肽水平。对乙酰氨基酚是一种常用的镇痛药。然而，过量服用对乙酰氨基酚会通过消耗肝脏中的谷胱甘肽而导致严重的肝毒性。在此，我们研究了大米肽对小鼠对乙酰氨基酚诱导的肝毒性的保护作用。将ICR小鼠口服给予大米肽（0、100或500mg/kg），持续7天，然后通过腹腔注射对乙酰氨基酚（700mg/kg）诱导肝毒性。用大米肽预处理可显著预防血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶和乳酸脱氢酶水平的升高，并防止肝脏谷胱甘肽耗竭。对乙酰氨基酚处理会降低谷胱甘肽合成中的关键调节酶γ-谷氨酰半胱氨酸合成酶的表达，尽管与对乙酰氨基酚处理相比，大米肽处理可使其表达恢复。此外，肝脏的组织病理学评估还显示，大米肽可预防对乙酰氨基酚诱导的小叶中心坏死。这些结果表明，大米肽可提高细胞内谷胱甘肽水平，并可保护小鼠免受对乙酰氨基酚诱导的肝毒性。
