Related Experiment Video
Updated: Aug 8, 2026
Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
Rosiglitazone ameliorates cisplatin-induced renal injury in mice
Sik Lee1, Won Kim, Sang-Ok Moon
1Department of Internal Medicine, Chonbuk National University Medical School, 634-18 Keum-Am Dong, Jeonju 561-712, Republic of Korea.
Background:
Inflammatory mechanisms may play an important role in the pathogenesis of cisplatin nephrotoxicity. Agonists of the peroxisome proliferator-activated receptor-gamma (PPARgamma), such as rosiglitazone, have been recently demonstrated to regulate inflammation by modulating the production of inflammatory mediators and adhesion molecules. The purpose of this study was to examine the protective effects of rosiglitazone on cisplatin nephrotoxicity and to explore the mechanism of its renoprotection.
Methods:
Mice were treated with cisplatin with or without pre-treatment with rosiglitazone. Renal functions, histological findings, aquaporin 2 (AQP2) and adhesion molecule expression, macrophage infiltration and tumour necrosis factor-alpha (TNF-alpha) levels were investigated. The effect of rosiglitazone on nuclear factor (NF)-kappaB activity and on viability was examined using cultured human kidney (HK-2) cells.
Results:
Rosiglitazone significantly decreased both the damage to renal function and histological pathology after cisplatin injection. Pre-treatment with rosiglitazone reduced the systemic levels of TNF-alpha and down-regulated adhesion molecule expression in addition to the infiltration of inflammatory cells after cisplatin administration. Rosiglitazone restored the decreased AQP2 expression after cisplatin treatment. Pre-treatment with rosiglitazone blocked the phosphorylation of the p65 subunit of NF-kappaB in cultured HK-2 cells. Rosiglitazone had a protective effect via a PPARgamma-dependent pathway in cisplatin-treated HK-2 cells.
Conclusion:
These results showed that pre-treatment with rosiglitazone attenuates cisplatin-induced renal damage through the suppression of TNF-alpha overproduction and NF-kappaB activation.
Insights
Rosiglitazone protects against cisplatin nephrotoxicity by reducing inflammation and activating protective pathways. This study shows rosiglitazone mitigates kidney damage by suppressing tumor necrosis factor-alpha and nuclear factor-kappaB activation.
Area of Science:
- Nephrology
- Pharmacology
- Immunology
Background:
- Inflammatory mechanisms are implicated in cisplatin-induced kidney damage.
- Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists, like rosiglitazone, modulate inflammatory responses.
- Understanding rosiglitazone's renoprotective mechanisms against cisplatin is crucial.
Purpose of the Study:
- To evaluate the protective effects of rosiglitazone against cisplatin nephrotoxicity.
- To investigate the underlying mechanisms of rosiglitazone's renoprotection.
Main Methods:
- Mice received cisplatin with or without rosiglitazone pre-treatment.
- Evaluated renal function, histology, aquaporin 2 (AQP2), adhesion molecules, and tumor necrosis factor-alpha (TNF-alpha).
- Assessed nuclear factor-kappaB (NF-kappaB) activity and cell viability in cultured human kidney (HK-2) cells.
Main Results:
- Rosiglitazone significantly reduced cisplatin-induced renal damage and improved renal function.
- It decreased TNF-alpha levels, adhesion molecule expression, and inflammatory cell infiltration.
- Rosiglitazone restored AQP2 expression and inhibited NF-kappaB activation in HK-2 cells, indicating a PPARgamma-dependent protective pathway.
Conclusions:
- Pre-treatment with rosiglitazone attenuates cisplatin-induced kidney damage.
- This protection is achieved by suppressing TNF-alpha overproduction and NF-kappaB activation.
- Rosiglitazone demonstrates significant renoprotective potential against cisplatin toxicity.
