Achillea millefolium ameliorates doxorubicin-induced renal injury via inhibition of oxidative stress and inflammation in rats

Résumé

Background/aim: Doxorubicin (Dox) is a potent anticancer medication. Nevertheless, due to nephrotoxicity, its clinical application is restricted. Achillea millefolium (AM) is a traditional medicine used against several disturbances, including kidney disorders. Therefore, this work aims to investigate the preventative properties of AM extract (AME) and their mechanisms against nephrotoxicity caused by Dox in rats. Materials and methods: The rats were assigned randomly to six groups, including a control group, Dox group (5 mg/kg/week via i.p. for 4 weeks), two groups, AME (100 or 200 mg/kg, orally for 28 days), and the last two groups, Dox+ AME (100 or 200 mg/kg, orally for 4 weeks). After the treatment period concluded, samples of blood and renal tissue were collected for analysis. Serum creatinine, urea, and uric acid levels were used to determine nephrotoxicity biochemically. In renal tissue samples, superoxide dismutase (SOD), catalase, glutathione (GSH), glutathione peroxidase (GPx), total antioxidant capacity (TAC), nitric oxide (NOx), tumor necrosis factor-alpha (TNF-α), interleukin1beta (IL-1β) and nuclear factor- kappa B (NF-κB) were measured. Histopathological analysis of the kidneys was also performed.Results: Dox caused a considerable increase in kidney function parameters and the occurrence of histological changes, which were significantly reversed by AME treatment. Mechanistically, Dox caused renal oxidative stress by raising malondialdehyde and nitric oxide levels while lowering superoxide dismutase, glutathione, glutathione peroxidase, and total antioxidant capacity. It also caused inflammation via the stimulation of pro-inflammatory cytokines in renal tissues. Conversely, the treatment of AME mitigated Dox-evoked abnormalities in the above-mentioned tests. Conclusion: AME could protect against nephrotoxicity caused by Dox by reducing oxidative stress, stimulating antioxidant mechanisms, and suppressing pro-inflammatory cytokines, suggesting that AME may be useful as an adjuvant therapy for Dox-induced nephrotoxicity.