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Mitigation of cyclophosphamide-induced nephrotoxicity by raspberry ketones through modulating oxidative stress,
Mahrous A Ibrahim1, Athar M Khalifa2, Heba N Gad El-Hak3
1Department of Internal Medicine (Forensic Medicine and Clinical Toxicology division), College of Medicine, Jouf University, Aljouf, Saudi Arabia.
Background:
Cyclophosphamide (CP) is an antineoplastic agent. Nevertheless, alongside its anticancer properties, CP may also induce renal toxicity. Raspberry ketone (RBK) is a naturally occurring phenolic compound having antioxidant and anti-inflammatory activities. However, its biological activity is not fully elucidated.
Aim Of The Study:
This study aimed to examine the potential mitigating benefits of raspberry ketones (RBKs), against CP-induced renal toxicity in rats.
Methods:
Thirty-six adult male, albino rats were randomly assigned into six groups (n = 6 each). Group I (the vehicle control group), Group II (RBK100), GroupIII (RBK200), Group IV (CP), Group V (CP+ RBK100), and Group VI (CP+ RBK200). At the end of the experimental process, serum creatinine and urea levels, antioxidant activity and lipid peroxidation products were assessed in renal tissues. Histopathological analysis and immunohistochemical labeling were conducted. Furthermore, PCR investigation and molecular docking were conducted.
Results:
CP induced renal damage, evidenced by elevated serum creatinine and urea, lipid peroxidation, pro-inflammatory cytokines, and up-regulated NF-κB, Keap-1, and caspase-3, along with histological alterations. RBKs ameliorated kidney function, prevented tissue damage, as well as significantly prevented oxidative stress, inflammation, and apoptosis by enhancing the antioxidant defenses and the upregulations of Nrf2, HO-1 and PPARγ, while downregulating the pro-apoptotic and pro-inflammatory markers NF-κB, Keap-1 and caspase-3. RBKs exhibited a reversal of the histological alterations. Molecular docking revealed that the combination of Cyclophosphamide and RBK might enhance therapeutic efficacy while potentially mitigating some of Cyclophosphamide's side effects through modulation of multiple cellular pathways.
Conclusion:
Raspberry ketones' antioxidants, anti-apoptotic, and anti-inflammatory properties may shield kidneys against CP toxicity. To ascertain the potential therapeutic uses of these discoveries in the future, additional experimental and clinical research is necessary.
