The Inhibitory Effect of Geraniol on CCL4-induced Hepatorenal Toxicity in Pregnant Mice through the PI3K/AKT Signaling Pathway

Author:

Alzahrani Sabah Ali1,Bekhet Gamal M.12,Ammar Rebai Ben13,Abdallah Basem M.1,Ali Enas Mohamed14,Al-Ramadan Saeed Y.5,Althumairy Duaa1,Rajendran Peramaiyan16

Affiliation:

1. Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa, Saudi Arabia

2. Department of Zoology, Faculty of Science, Alexandria University Egypt, Alexandria, Egypt

3. Laboratory of Aromatic and Medicinal Plants, Center of Biotechnology of Borj Cedria, Hammam-Lif, Tunisia

4. Department of Botany and Microbiology, Faculty of Science, Cairo University, Cairo, Egypt

5. Department of Anatomy, College of Veterinary Medicine, King Faisal University, Al-Ahsa, Saudi Arabia

6. Department of Biochemistry, Centre of Molecular Medicine and Diagnostics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India

Abstract

Abstract Background: Hepatotoxicity caused by CCL4 is well known. Geraniol (GNL) has high antioxidant effect that can induces liver regeneration. However, the protective effect of GNL effect on CCL4-induced hepatorenal toxicity in pregnant mice has not yet been studied. Objective: To investigate whether GNL could protect against oxidative stress induced by CCL4 via the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, which is regulated by phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT), and has been found to have protective effects on renal and hepatic tissues. Materials and Methods: Forty-eight female albino mice weighing 25–30 g were randomly allocated to 4 groups: Group I served as a control; Group II received a toxicity-inducing single dose of 15 μL of CCL4 on the 4th day after mating; Group III received 40 mg/kg GNL + CCL4 (with GNL from the 1st day of assimilation to delivery); and Group IV received GNL alone from the 1st day of assimilation to the end of the delivery period. GNL was evaluated for its protective effects on hepatotoxicity in CCL4-treated pregnant mice. Litter size, weight, survival rate, and resorption were recorded. In addition, H & E staining was done for liver and kidney pathology as well as biochemical markers and oxidative markers malondialdehyde, superoxide dismutase, and catalase were analyzed. Results: CCL4 significantly reduced survival rate and increased resorption after exposure. Alanine transaminase and aspartate aminotransferase concentrations in the serum, tissue MDA, blood urea nitrogen, and creatinine were increased after CCL4 exposure. GNL improved enzyme and antioxidant levels and prevented CCL4-induced hepatic injury in mice. Caspase-3 cleavage was decreased by GNL, which increased PI3K, phosphorylated AKT, Nrf2, and B-cell lymphoma 2. Conclusion: GNL demonstrates a protective effect against CCl4-induced hepatorenal toxicity, mediated through the activation of the PI3K/AKT signaling pathway and the upregulation of Nrf2. These findings highlight the potential therapeutic implications of GNL in mitigating oxidative stress and inflammation in liver and kidney tissues.

Publisher

Medknow

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