Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, Egypt.
Department of Pathology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt.
PLoS One. 2022 Mar 18;17(3):e0265261. doi: 10.1371/journal.pone.0265261. eCollection 2022.
Hydroxyurea (HDU) is a widely used medication for various malignancies, thalassemia, and sickle cell anemia with reported side effects. The current study investigated HDU- induced hepatic injury and the protective potential of the royal jelly (RJ) against this hepatotoxic effect in the light of hepatic oxidative/ antioxidative status, pro-inflammatory cytokine, apoptosis signaling pathway, and histopathology. Sixty albino rats were used (n = 10/group) for 60 days: control, RJ (100 mg/kg body weight, orally), HDU (225 mg/kg body weight, orally), 2HDU (450 mg/kg body weight, orally), and HDU + RJ groups. HDU-treated rats showed significant elevation of liver function tests as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, as well as malondialdehyde and nitric oxide (oxidative biomarkers) and significant decreased hepatic antioxidant molecules (reduced glutathione, superoxide dismutase, and glutathione peroxidase), compared to a control group, that more pronounced in the high dose of HDU. In addition, HDU induced significant upregulation of TNF-α and the Caspase-3 apoptotic pathway. Moreover, the liver of HDU treated groups showed various hepatic lesions from mild to severe necrotic changes related to the HDU dose. However, administration of RJ with HDU improved liver function tests, liver histology, and hepatic oxidative/antioxidative status concerning HDU groups. Furthermore, oral RJ administration with HDU significantly lessens the immune-expression area % of TNF-α and Caspase-3. Thus, the royal jelly has antioxidant, anti-inflammatory, and anti-apoptotic properties against HDU- induced hepatic injury and could be, therefore, used as adjuvant therapy in patients with long-term HDU medication.
羟脲（HDU）是一种广泛用于多种恶性肿瘤、地中海贫血和镰状细胞贫血的药物，有报道称其有副作用。本研究根据肝氧化/抗氧化状态、促炎细胞因子、细胞凋亡信号通路和组织病理学，研究了 HDU 诱导的肝损伤以及蜂王浆（RJ）对这种肝毒性的保护作用。60 只白化大鼠（n = 10/组）用于 60 天：对照组、RJ（100mg/kg 体重，口服）、HDU（225mg/kg 体重，口服）、2HDU（450mg/kg 体重，口服）和 HDU+RJ 组。与对照组相比，HDU 处理的大鼠的肝功能试验（天门冬氨酸氨基转移酶、丙氨酸氨基转移酶和碱性磷酸酶）以及丙二醛和一氧化氮（氧化生物标志物）显著升高，肝抗氧化分子（还原型谷胱甘肽、超氧化物歧化酶和谷胱甘肽过氧化物酶）显著降低，在高剂量的 HDU 中更为明显。此外，HDU 诱导了 TNF-α 和 Caspase-3 凋亡途径的显著上调。此外，HDU 处理组的肝脏表现出从轻到重的各种肝损伤，与 HDU 剂量有关。然而，用 RJ 与 HDU 联合给药可改善与 HDU 组相关的肝功能试验、肝组织学和肝氧化/抗氧化状态。此外，与 HDU 联合口服 RJ 可显著减少 TNF-α 和 Caspase-3 的免疫表达面积%。因此，蜂王浆具有抗氧化、抗炎和抗细胞凋亡特性，可预防 HDU 诱导的肝损伤，因此可作为长期使用 HDU 药物的患者的辅助治疗。
