Possible beneficial effect of peroxisome proliferator-activated receptor (PPAR) — α and γ agonist against a rat model of oral dyskinesia

The pharmacological induction and activation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), a key regulator of ischemic brain tolerance, is a promising direction in neuroprotective therapy. Pharmacological agents with known abilities to modulate cerebral PGC-1α are scarce. This study focused on the potential PGC-1α-modulating activity of Mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) and Semax (ACTH(4–7) analog) in a rat model of photochemical-induced thrombosis (PT) in the prefrontal cortex. Mexidol (100 mg/kg) was administered intraperitoneally, and Semax (25 μg/kg) was administered intranasally, for 7 days each. The expression of PGC-1α and PGC-1α-dependent protein markers of mitochondriogenesis, angiogenesis, and synaptogenesis was measured in the penumbra via immunoblotting at Days 1, 3, 7, and 21 after PT. The nuclear content of PGC-1α was measured immunohistochemically. The suppression of PGC-1α expression was observed in the penumbra from 24 h to 21 days following PT and reflected decreases in both the number of neurons and PGC-1α expression in individual neurons. Administration of Mexidol or Semax was associated with preservation of the neuron number and neuronal expression of PGC-1α, stimulation of the nuclear translocation of PGC-1α, and increased contents of protein markers for PGC-1α activation. This study opens new prospects for the pharmacological modulation of PGC-1α in the ischemic brain.

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Glucose Transporter 4 and Peroxisome Proliferator-Activated Receptor-Alpha Overexpression Association With Cardioprotective Effects of Myoinositol and Metformin Combination in Type 2 Diabetic Rat Model

Journal of Endocrinology and Metabolism ◽

10.14740/jem765 ◽

2021 ◽

Vol 11 (5) ◽

pp. 140-151

Author(s):

Dalia Abdel-Wahab Mohamed ◽

Wael M. Elayat ◽

Asmaa A. Abozeid ◽

Mohamed F. Abdel-Salam ◽

Nahla Mohamed Teama ◽

...

Keyword(s):

Rat Model ◽

Glucose Transporter ◽

Diabetic Rat ◽

Peroxisome Proliferator ◽

Glucose Transporter 4 ◽

Peroxisome Proliferator Activated Receptor ◽

Cardioprotective Effects ◽

Diabetic Rat Model ◽

Type 2 Diabetic

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Fenofibrate Improved Interstitial Fibrosis of Renal Allograft through Inhibited Epithelial-Mesenchymal Transition Induced by Oxidative Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/8936856 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Yishu Wang ◽

Lei Pang ◽

Yanghe Zhang ◽

Jiahui Lin ◽

Honglan Zhou

Keyword(s):

Oxidative Stress ◽

Rat Model ◽

Renal Allograft ◽

Epithelial Mesenchymal Transition ◽

Interstitial Fibrosis ◽

Peroxisome Proliferator ◽

Tubular Atrophy ◽

Peroxisome Proliferator Activated Receptor ◽

Mesenchymal Transition ◽

Stage Renal Disease

The best treatment for end-stage renal disease is renal transplantation. However, it is often difficult to maintain a renal allograft healthy for a long time following transplantation. Interstitial fibrosis and tubular atrophy (IF/TA) are significant histopathologic characteristics of a compromised renal allograft. There is no effective therapy to improve renal allograft function once IF/TA sets in. Although there are many underlying factors that can induce IF/TA, the pathogenesis of IF/TA has not been fully elucidated. It has been found that epithelial-mesenchymal transition (EMT) significantly contributes to the development of IF/TA. Oxidative stress is one of the main causes that induce EMT in renal allografts. In this study, we have used H2O2 to induce oxidative stress in renal tubular epithelial cells (NRK-52e) of rats. We also pretreated NRK-52e cells with an antioxidant (N-acetyl L-cysteine (NAC)) 1 h prior to the treatment with H2O2. Furthermore, we used fenofibrate (a peroxisome proliferator-activated receptor α agonist) to treat NRK-52e cells and a renal transplant rat model. Our results reveal that oxidative stress induces EMT in NRK-52e cells, and pretreatment with NAC can suppress EMT in these cells. Moreover, fenofibrate suppresses fibrosis by ameliorating oxidative stress-induced EMT in a rat model. Thus, fenofibrate may effectively prevent the development of fibrosis in renal allograft and improve the outcome.

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