Antioxidant Potential and Oxidative Stress Modulation of Geranium macrorrhizum L. Oil Extract in Gentamicin-Induced Nephrotoxicity

<b>Objectives:</b> The current study focused on the kidney protection and antioxidant properties along with the potential anti-ferroptotic activity of <i>Geranium macrorrhizum</i> L. (<i>G. macrorrhizum</i>) oil to ameliorate the acute renal oxidative tissue damage and toxicity of the aminoglycoside antibiotic gentamicin (GM) in an experimental murine model. <b>Methods:</b> The research was carried out with mature Balb/c mice distributed into four groups (n = 6). Application of GM (200 mg kg^-1 intraperitoneal injection for 10 days) was performed to induce kidney injury. Only saline was administered to the controls. The remaining groups were administered <i>G. macrorrhizum</i> oil (50 mg kg^-1 per dose) either used alone or in combination with GM. To assess the renal antioxidant status, the activities of specific antioxidant enzymes, indicators of lipid and DNA peroxidation and renal functional damage were examined using standard commercial kits, ELISA and EPR spectroscopy. <b>Results:</b><i>G. macrorrhizum</i> oil analysis revealed 20 organic components belonging to mono- and sesquiterpenoids and long-chain hydrocarbons. The antioxidant and anti-inflammatory effects of <i>G. macrorrhizum</i> oil were demonstrated by reduced malondialdehyde, ROS, 8-hydroxy-2'-deoxyguanosine and cytokine levels (especially interleukin-1β) compared with GM. Furthermore, increased activation of superoxide dismutase, catalase and glutathione (GSH) were observed in the kidney homogenates of the animals which received GM in combination with <i>G. macrorrhizum</i> oil compared with the GM group. Additional changes in the GSH/glutathione peroxidase-4 axis were detected, suggesting the possible anti-ferroptotic potential of the oil. Nephroprotection was also demonstrated by elevated PGC-1α expression (peroxisome proliferator-activated receptor γ coactivator 1-alpha) and reduced KIM-1 levels (kidney injury molecule-1) following application of the oil. <b>Conclusions:</b> The preserved kidney antioxidant and functional properties in the groups treated with oil suggest that <i>Geranium macrorrhizum</i> L. could be utilized clinically to mitigate the toxic effects of GM application.