Alkuwayti Mayyadah Abdullah
Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa, Saudi Arabia.
J Biochem Mol Toxicol. 2025 Aug;39(8):e70408. doi: 10.1002/jbt.70408.
Ochratoxin A (OTA) is a hepatotoxin that has considerable public health consequences. This study examined the protective benefits of isoliquiritigenin (ISL) against OTA-induced hepatic toxicity in Swiss albino mice, with a focus on the Nrf2 signalling pathway. The mice were categorized into four groups: Group I (control): single daily dose of 0.05% DMSO was administered for 6 weeks. Group II (OTA): treatment with OTA at a dosage of 25 mg/kg body weight three times per week. Group III (OTA + ILS): treatment with OTA (25 mg/kg, three times per week) in combination with ILS at a single dose of 75 mg/kg daily (oral gavage). Group IV (ILS): treatment with ILS alone at a single dose of 75 mg/kg daily. The injection of OTA increased the levels of liver enzyme markers, indicating hepatic damage. Moreover, OTA elicited oxidative stress, as demonstrated by elevated lipid peroxidation and diminished antioxidant enzyme activity. OTA blocked the PI3K/AKT/Nrf2 signalling pathway, which led to lower levels of Nrf2 target genes such as haem oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1). Furthermore, OTA disturbed the equilibrium between apoptosis and survival, as shown by increased PARP cleavage and cleaved caspase-3, as well as decreased Bcl-2 expression. In contrast, ISL treatment in OTA-treated mice significantly reduced the liver enzymes, decreased oxidative stress, and restored PI3K/AKT/Nrf2 signalling. ISL also increased Nrf2, HO-1, NQO1, and Bcl-2 while reducing PARP cleavage and cleaved caspase-3. These findings indicate that ISL mitigates OTA-induced liver damage by activating the Nrf2 signaling pathway, thereby reducing oxidative stress and cellular apoptosis.
赭曲霉毒素A（OTA）是一种具有重大公共卫生影响的肝毒素。本研究考察了异甘草素（ISL）对瑞士白化小鼠OTA诱导的肝毒性的保护作用，重点关注Nrf2信号通路。小鼠被分为四组：第一组（对照组）：每天单次给予0.05%二甲亚砜，持续6周。第二组（OTA组）：以25mg/kg体重的剂量每周三次给予OTA治疗。第三组（OTA + ILS组）：以25mg/kg（每周三次）的剂量给予OTA，并联合每天单次75mg/kg的ILS（经口灌胃）治疗。第四组（ILS组）：每天单次给予75mg/kg的ILS单独治疗。注射OTA增加了肝酶标志物水平，表明肝脏受损。此外，OTA引发了氧化应激，脂质过氧化升高和抗氧化酶活性降低证明了这一点。OTA阻断了PI3K/AKT/Nrf2信号通路，导致Nrf2靶基因如血红素加氧酶-1（HO-1）和NAD（P）H醌脱氢酶1（NQO1）的水平降低。此外，OTA扰乱了细胞凋亡与存活之间的平衡，PARP裂解增加、半胱天冬酶-3裂解增加以及Bcl-2表达降低表明了这一点。相比之下，在OTA处理的小鼠中进行ISL治疗显著降低了肝酶，减轻了氧化应激，并恢复了PI3K/AKT/Nrf2信号传导。ISL还增加了Nrf2、HO-1、NQO1和Bcl-2，同时减少了PARP裂解和半胱天冬酶-3裂解。这些发现表明，ISL通过激活Nrf2信号通路减轻OTA诱导的肝损伤从而减少氧化应激和细胞凋亡。
