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Published on: January 7, 2013
Agomelatine on cisplatin-induced nephrotoxicity via oxidative stress and apoptosis
Eyup Dil1, Atilla Topcu2, Tolga Mercantepe3
1Department of Urology Faculty of Medicine, Recep Tayyip Erdogan University, 2 Nolu Sehitler Street, Rize, 53010, Turkey. eyup.dil@erdogan.edu.tr.
Abstract:
Drug-induced nephrotoxicity is the greatest deterrent to the use of cisplatin, which is a frequently used chemotherapeutic with proven effectiveness in cancer therapy. Agomelatine, which is used in the treatment of sleep disorders and depression, has gained attention in recent years with its antioxidative and anti-inflammatory effects. In this study, the effects of the synthetic melatonin agonist agomelatine on nephrotoxicity were investigated in a rat model of cisplatin-induced nephrotoxicity using biochemical, histological, and immunohistochemical methods. Thirty-two male rats were divided into 4 groups: 1. control group, 2. agomelatine group, 3. cisplatin group, 4. cisplatin + agomelatine group. In the cisplatin group, there were widespread atypical glomerular structures and vacuolization in tubular epithelial cells, necrotic tubules, deterioration of brush border structure in proximal tubules, and fibrotic areas characterized by diffuse polymorphonuclear leukocyte (PNL) and extensive collagen deposition in the interstitial spaces. However, in the cisplatin + agomelatine group, we observed a reduction in glomeruli of atypical structure and necrotic tubules, in PNL infiltration in interstitial spaces, and fibrotic areas compared to the cisplatin group. The cisplatin + agomelatine group showed lower malondialdehyde (MDA) serum creatinine, serum urea levels, and higher glutathione (GSH) levels compared to the cisplatin group. Immunohistochemical analyses revealed that the elevated NF-kβ/p65, 8-OHdG, and cleaved caspase-3 positivity in the cisplatin group had significantly decreased in the cisplatin + agomelatine group. In conclusion, agomelatine showed a nephroprotective effect against cisplatin-induced nephrotoxicity.
Insights
Agomelatine, an antioxidant, demonstrated significant nephroprotective effects against cisplatin-induced kidney damage in rats. This study highlights agomelatine
Area of Science:
- Pharmacology
- Nephrology
- Oncology
Background:
- Cisplatin is a vital chemotherapy drug, but its use is limited by severe nephrotoxicity.
- Agomelatine, known for its antioxidant and anti-inflammatory properties, is used for sleep and depression disorders.
Purpose of the Study:
- To investigate the protective effects of agomelatine against cisplatin-induced nephrotoxicity in a rat model.
- To evaluate the impact of agomelatine on kidney function and histological damage.
Main Methods:
- A rat model was used, with groups receiving control, agomelatine, cisplatin, or cisplatin + agomelatine.
- Biochemical markers (serum creatinine, urea, MDA, GSH), histological analysis, and immunohistochemical staining (NF-κβ/p65, 8-OHdG, cleaved caspase-3) were employed.
Main Results:
- Cisplatin induced significant kidney damage, including glomerular and tubular alterations, inflammation, and fibrosis.
- Agomelatine treatment reduced these histological changes, decreased oxidative stress markers (MDA), and increased antioxidant levels (GSH).
- Agomelatine significantly lowered elevated levels of NF-κβ/p65, 8-OHdG, and cleaved caspase-3.
Conclusions:
- Agomelatine exhibits significant nephroprotective properties against cisplatin-induced kidney injury.
- The findings suggest agomelatine may mitigate chemotherapy-related kidney damage through its antioxidant and anti-inflammatory mechanisms.
