AMELIORATIVE EFFECTS OF GERANIOL ON CYCLOPHOSPHAMIDE-INDUCED NEPHROTOXICITY: EVIDENCE FROM NUCLEAR FACTOR ERYTHROID 2-RELATED FACTOR 2 (NRF-2) ACTIVATION AND APOPTOSIS MODULATION

Halime Tuba CANBAZ, Mehmet Enes SOZEN, Furkan Adem CANBAZ, Gokhan CUCE, Serpil KALKAN

The European Research Journal - 2026;12(8):867-875

Department of Histology and Embryology, University of Health Sciences, Hamidiye Faculty of Medicine, İstanbul, Türkiye

 

Objective: The cyclophosphamide (CP)-related nephrotoxicity may impede cancer treatment. This study investigated the efficacy of geraniol (Ge) at two doses against CP nephrotoxicity. Methods: Fourty-two Wistar albino rats were allocated into six groups (n=7 each group): Group I, control; Group II, CP; Group III, CP+Ge 100 mg/kg; Group IV , CP+Ge 200 mg/kg; Group V , Ge 100 mg/kg; and Group VI, Ge 200 mg/kg. At the end of study, alterations in renal tissues were evaluated using hematoxylin-eosin and histopathological scores were determined. Masson's trichrome and Periodic acid-Schiff (PAS) staining were also performed for evaluation of fibrosis, parietal layer of Bowman capsule, and Bowman's space. Immunofluorescence analysis assessed oxidative stress and apoptosis. Consequently, the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf-2), caspase 3, and caspase 9 were evaluated. Results: CP caused the histopathological changes, including tubular damage, glomerular degeneration, interstitial inflammation. Ge restored the increased histopathological scores, parietal layer of Bowman capsule, and Bowman's space caused by CP without dose dependence (P<0.001 for both dose). CP decreased the expression of Nrf-2, while Ge improved this disturbance with greater efficacy at a higher dose (P<0.001 for all). CP exposure increased both caspase 3 and caspase 9 (P<0.001 for both). Ge decreased the expressions of caspase 3 and caspase 9 at two doses (P<0.001 for all). In addition, Ge was more effective in repairing caspase 3 at a higher dose (P=0.006). Conclusion: Ge seems to effectively reverse CP-induced nephrotoxicity. The histopathological improvements are mediated by mechanisms involving the attenuation of oxidative stress and apoptosis. The efficacy of Ge is also dose-dependent.