Rana K El-Asfar1, Marwa O El-Derany1, Al-Aliaa M Sallam2, Sara A Wahdan3, Ebtehal El-Demerdash3, Sayed A Sayed4, Hala O El-Mesallamy5. 1. Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. 2. Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; Department of Biochemistry, School of Pharmacy and Pharmaceutical Industries, Badr University in Cairo (BUC), Entertainment Area, Badr City, Cairo, 11829, Egypt. 3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. 4. Department of Pathology, Al-Azhar Faculty of Medicine, Cairo, Egypt. 5. Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; Department of Biochemistry, School of Pharmacy, Sinai University, Sinai, Egypt. Electronic address: hala_elmosalamy@hotmail.com.
Abstract
BACKGROUND AND AIM: Tamoxifen (TAM) therapy has been associated with fatty liver diseases. Recently, multiple reports have also shown that TAM is related to cognitive impairment in patients with breast cancer. Luteolin, a natural flavonoid, has been traditionally used to treat various inflammatory disorders, such as chronic liver diseases, cognitive impairments, and cancers. This study aimed to evaluate the potential protective effects of luteolin against the cognitive defects and liver steatosis induced by TAM in rats. EXPERIMENTAL APPROACH: The diseased group was subcutaneously (s.c) injected with TAM at a dose of 1 mg/kg daily for 7 days. The cotreated groups were given luteolin via oral gavage at a dose of 20 or 40 mg/kg concomitantly with s.c injection of TAM at a dose of 1 mg/kg for 7 days. All the groups were subjected to behavioral tests 24 h after the last TAM injection. Then, the rats were sacrificed 3 days after the last TAM injection. RESULTS: Luteolin cotreatment significantly alleviated the behavioral defects in rats with TAM-induced cognitive impairment. This finding was supported by the reversal of neurodegeneration in the cortex and in the hippocampal regions of the brain. Furthermore, luteolin attenuated hepatic steatosis and decreased the levels of serum aminotransferases and hypertriglyceridemia. As an anti-inflammatory agent, luteolin cotreatment similarly decreased the levels of hepatic inflammatory markers and increased the levels of hepatic β-catenin in TAM-induced fatty liver. CONCLUSIONS: Luteolin improved the TAM-induced cognitive impairment and hepatic steatosis in rats by alleviating inflammation and modulating hepatic β-catenin levels.
BACKGROUND AND AIM: Tamoxifen (TAM) therapy has been associated with fatty liver diseases. Recently, multiple reports have also shown that TAM is related to cognitive impairment in patients with breast cancer. Luteolin, a natural flavonoid, has been traditionally used to treat various inflammatory disorders, such as chronic liver diseases, cognitive impairments, and cancers. This study aimed to evaluate the potential protective effects of luteolin against the cognitive defects and liver steatosis induced by TAM in rats. EXPERIMENTAL APPROACH: The diseased group was subcutaneously (s.c) injected with TAM at a dose of 1 mg/kg daily for 7 days. The cotreated groups were given luteolin via oral gavage at a dose of 20 or 40 mg/kg concomitantly with s.c injection of TAM at a dose of 1 mg/kg for 7 days. All the groups were subjected to behavioral tests 24 h after the last TAM injection. Then, the rats were sacrificed 3 days after the last TAM injection. RESULTS: Luteolin cotreatment significantly alleviated the behavioral defects in rats with TAM-induced cognitive impairment. This finding was supported by the reversal of neurodegeneration in the cortex and in the hippocampal regions of the brain. Furthermore, luteolin attenuated hepatic steatosis and decreased the levels of serum aminotransferases and hypertriglyceridemia. As an anti-inflammatory agent, luteolin cotreatment similarly decreased the levels of hepatic inflammatory markers and increased the levels of hepatic β-catenin in TAM-induced fatty liver. CONCLUSIONS: Luteolin improved the TAM-induced cognitive impairment and hepatic steatosis in rats by alleviating inflammation and modulating hepatic β-catenin levels.