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Updated: Jun 11, 2025
Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
CGS-21680 defers cisplatin-induced AKI-CKD transition in C57/BL6 mice
Menna A Elbrolosy1, Manar G Helal1, Mirhan N Makled1
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Abstract:
Acute kidney injury (AKI), with a high mortality and morbidity, is known as a risk factor for developing progressive chronic kidney disease (CKD). Targeting transition of AKI to CKD displays an excellent therapeutic potential. This study aims at investigating the role of CGS-21680, selective A2AR agonist, in deferring Cis-induced AKI-CKD transition. The AKI-CKD transition model was induced in C57/BL6 mice by repeated low doses of Cis (2.5 mg/kg i.p for 5 consecutive days in two cycles with a recovery phase of 16 days between two cycles). CGS-21680 was administered daily for 6 weeks (0.1 mg/kg, i.p). Urine, blood, and kidney were collected at three different time points to track the disease progression. CGS-21680 administration preserved kidney function and attenuated tubular damage as evidenced by hematoxylin-eosin (H&E) histopathology. CGS-21680 significantly restored oxidative status as reflected by reduced malondialdehyde (MDA) content and increased total antioxidant capacity (TAC). CGS-21680 showed anti-inflammatory effect as indicated by decreased TNF-α and iNOS. Additionally, CGS-21680 ameliorated endothelial dysfunction and enhanced renal vasodilation as evidenced by upregulation of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) expression and down regulation of endothelin-1 (ET-1) and its receptor endothelin-A (ET-A) receptor expression. CGS-21680 also attenuated renal fibrosis as reflected by the reduction of percentage of fibrosis in Masson's trichome-stained renal sections and down regulation of transforming growth factor beta1 (TGF-β1) protein expression in IHC-stained renal sections. In conclusion, CGS-21680 could defer Cis-induced AKI-CKD transition via its vasodilatory, antioxidant, anti-inflammatory, and anti-fibrotic effects.
Insights
CGS-21680, an A2AR agonist, delays the progression from acute kidney injury (AKI) to chronic kidney disease (CKD). This compound offers therapeutic potential by reducing kidney damage, inflammation, and fibrosis in a cisplatin-induced mouse model.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Acute kidney injury (AKI) is a significant risk factor for developing progressive chronic kidney disease (CKD).
- Targeting the transition from AKI to CKD presents a promising therapeutic strategy.
- Cisplatin (Cis) is a nephrotoxic agent commonly used in chemotherapy, which can induce AKI.
Purpose of the Study:
- To investigate the potential of CGS-21680, a selective adenosine A2A receptor (A2AR) agonist, in preventing the transition from cisplatin-induced AKI to CKD.
- To evaluate the protective effects of CGS-21680 on kidney function and structure in a mouse model.
Main Methods:
- An AKI-CKD transition model was established in C57/BL6 mice using repeated low doses of cisplatin.
- CGS-21680 was administered daily for six weeks to assess its therapeutic effects.
- Kidney function, oxidative stress, inflammation, endothelial dysfunction, and fibrosis were evaluated at multiple time points.
Main Results:
- CGS-21680 administration preserved kidney function and attenuated tubular damage.
- The treatment significantly restored oxidative status, reduced inflammation (decreased TNF-α, iNOS), and ameliorated endothelial dysfunction (upregulated eNOS, NO; downregulated ET-1, ET-A).
- CGS-21680 effectively attenuated renal fibrosis and downregulated TGF-β1 expression.
Conclusions:
- CGS-21680 demonstrates significant potential in deferring cisplatin-induced AKI-to-CKD transition.
- The protective effects are attributed to its vasodilatory, antioxidant, anti-inflammatory, and anti-fibrotic properties.
- CGS-21680 represents a promising therapeutic candidate for preventing CKD progression after AKI.
