Isoliquiritigenin Attenuates Ochratoxin A-Induced Hepatic Oxidative Stress and Toxicity Through the PI3K/AKT/Nrf2 Pathway in Swiss Albino Mice.

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.