Protective potential of royal jelly against hydroxyurea -induced hepatic injury in rats via antioxidant, anti-inflammatory, and anti-apoptosis properties

• Published in: PloS one Vol. 17; no. 3; p. e0265261
• Main Authors: Tohamy, Hossam G, El-Neweshy, Mahmoud S, Soliman, Mohamed Mohamed, Sayed, Samy, Shukry, Mustafa, Ghamry, Heba I, Abd-Ellatieff, Hoda
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.03.2022; Public Library of Science (PLoS)
• Subjects: Alanine; Alanine transaminase; Alkaline phosphatase; Anemia; Animals; Anti-Inflammatory Agents - metabolism; Anti-Inflammatory Agents - pharmacology; Antioxidants; Antioxidants - metabolism; Antioxidants - pharmacology; Apoptosis; Aspartate aminotransferase; Biology and Life Sciences; Biomarkers; Body Weight; Cancer therapies; Care and treatment; Caspase 3 - metabolism; Caspase-3; Complications and side effects; Cytokines; Cytotoxicity; Drug dosages; Enzymes; Fatty Acids; Glutathione; Glutathione peroxidase; Histology; Histopathology; Humans; Hydroxyurea; Hydroxyurea - pharmacology; Inflammation; Injuries; Laboratory animals; Liver; Liver - metabolism; Liver diseases; Malondialdehyde; Medicine and Health Sciences; Melanoma; Nitric oxide; Oxidative Stress; Pathology; Patient outcomes; Peroxidase; Phosphatase; Properties; Rats; Research and Analysis Methods; Royal jelly; Sickle cell anemia; Sickle cell disease; Side effects; Signal transduction; Skin cancer; Superoxide dismutase; Thalassemia; Transaminases; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Veterinary medicine; Egypt; Saudi Arabia; Netherlands; Alexandria Egypt
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0265261

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.