Ibuprofen attenuates nephropathy in streptozotocin‑induced diabetic rats

Liu,Yao‑Wu; Zhu,Xia; Cheng,Ya‑Qin; Lu,Qian; Zhang,Fan; Guo,Hao; Yin,Xiao‑Xing

doi:10.3892/mmr.2016.5150

Ibuprofen attenuates nephropathy in streptozotocin‑induced diabetic rats

Authors:
- Yao‑Wu Liu
- Xia Zhu
- Ya‑Qin Cheng
- Qian Lu
- Fan Zhang
- Hao Guo
- Xiao‑Xing Yin
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Affiliations: Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu 221004, P.R. China
Published online on: April 20, 2016 https://doi.org/10.3892/mmr.2016.5150
Pages: 5326-5334

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Abstract

Ibuprofen, a commonly administered nonsteroidal anti‑inflammatory therapeutic agent, is also a partial agonist of peroxisome proliferator‑activated receptor γ (PPARγ). The present study investigated the effects of ibuprofen on type 1 diabetic nephropathy (DN) in rats, and the potential mechanisms associated with the activation of PPARγ. Diabetic rats were induced through a single intraperitoneal injection of streptozotocin before oral treatment with ibuprofen or pioglitazone for 8 weeks. The 24‑h urine collection was performed for measurement of total protein content. The kidney was fixed in 10% formalin for periodic acid‑Schiff and Masson's trichrome staining. Blood and residual kidney tissue samples were collected to measure the associated biochemical parameters. Chronic ibuprofen treatment decreased urinary protein excretion, blood urea nitrogen, glomerular basement membrane thickening and renal fibrosis, which were accompanied by increases in PPARγ protein expression, glutathione (GSH) level, and superoxide dismutase (SOD) activity, decreases in cyclooxygenase 2 and inducible nitric oxide synthase protein expressions, as well as a decreased interleukin 1β (IL‑1β) level in the renal cortex of DN rats. Furthermore, the reduced IL‑1β level, increased GSH quantities and stronger SOD activity in the rat serum were evaluated in ibuprofen‑treated diabetic rats and were compared with untreated diabetic rats. Regarding GSH and IL‑1β levels, ibuprofen was identified to be superior to the positive control, pioglitazone, while levels of the other indices were identified to be similar. Thus, ibuprofen was observed to prevent the development of DN, caused by type 1 diabetes, by anti‑inflammatory and anti‑oxidative action, potentially via PPARγ activation.

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