scholarly journals Pioglitazone, a Peroxisome Proliferator-Activated Receptor γ Agonist, Ameliorates Chronic Kidney Disease by Enhancing Antioxidative Capacity and Attenuating Angiogenesis in the Kidney of a 5/6 Nephrectomized Rat Model

2016 ◽  
Vol 38 (5) ◽  
pp. 1831-1840 ◽  
Author(s):  
Li Sun ◽  
Quan Yuan ◽  
Tianhua Xu ◽  
Li Yao ◽  
Jiangmin Feng ◽  
...  
Keyword(s):  
Rat Model ◽  
Ischemia Reperfusion Injury ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Periodic Acid ◽  
Peroxisome Proliferator ◽  
Antioxidative Capacity ◽  
Periodic Acid Schiff ◽  
Peroxisome Proliferator Activated Receptor ◽  
Injured Kidney

Background/Aims: Pioglitazone is a type of peroxisome proliferator-activated receptor γ agonist and is capable of alleviating renal ischemia-reperfusion injury. Methods: A5/6 nephrectomized rat model was established to induce renal impairments mimicking chronic kidney diseases (CKDs). The effect of pioglitazone on renal structure, function, antioxidative capacity, and angiogenesis in the nephrectomized rats was assessed. Moreover, the expression of HIF-1α, eNOS, VEGF, Flt-1 and Flk-1 was determined to reveal the possible pathways through which pioglitazone exerted its beneficial effect on CKDs. Results: Subtotal nephrectomy caused severe damages to rat renal tissues, and administration of pioglitazone dramatically restored the structure and function of the kidney, which was evidenced by Periodic acid- Schiff staining and the reduced levels of urinary proteins, blood urea nitrogen, and creatinine. Furthermore, pioglitazone decreased the level of malondialdehyde and increased the level of superoxide dismutase in the injured renal tissues, suggesting that the antioxidative capacity in the injured kidney was augmented by pioglitazone. Additionally, pioglitazone inhibited HIF-1α-dependent angiogenesis by down-regulating the expression of a panel of angiogenic factors. Conclusion: The current study demonstrates that pioglitazone benefits renal failure through activation of the antioxidative system and inhibition of angiogenesis in the injured kidney. Our study provides preliminary evidences for the potential application of this agent in the treatment of CKDs.

EFFECTS OF MELATONIN AND CURCUMIN TREATMENTS ON THE OVARIUM IN KIDNEY ISCHEMIA-REPERFUSION INJURY: A HISTOPATHOLOGICAL INVESTIGATION

2021 ◽  
Vol 6 (15) ◽  
pp. 45-51
Author(s):  
Ayşe Köse Vuruşkan ◽  
Nur ELAGÜL ◽  
Tansel SAPMAZ ◽  
Sude TOPKARAOĞLU
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Periodic Acid ◽  
Control Group ◽  
Histological Structure ◽  
Periodic Acid Schiff ◽  
Group I ◽  
Vascular Congestion ◽  
Reperfusion Period ◽  
Female Wistar Rats

Aim: We aimed to investigate how bilateral renal ischemia-reperfusion (I/R) damage affects the ovaries as a distant organ and the effects of melatonin (MEL), curcumin (CUR) and melatonin+curcumin (MEL+CUR) treatments on I/R damage. Material and Method: 42 female Wistar rats were used in the study. Rats were divided into 6 groups and study was designed as follows: Control group (G1) – opening and closing the abdomen only (sham surgery group) –, I/R group (G2) – 45 min ischemia followed by 2 h reperfusion –, I/R+MEL group (G3) – 45 min ischemia, intraperitoneal (i.p) 20 mg/kg MEL injection 5 min before reperfusion, followed by 2 h reperfusion –, I/R+CUR group (G4) – 45 min ischemia, 5 min before reperfusion i.p 200 mg/kg CUR injection and then 2 hours reperfusion –, I/R+MEL+CUR group (G5) – 45 min ischemia, 5 min before reperfusion i.p 20 mg/kg MEL and 200 mg/kg CUR injection, followed by 2 hours reperfusion –. At the end of the reperfusion period, the rats were sacrificed. Right ovaries were removed from the peritoneum and fixed. After fixation and follow-up, tissue sections were stained with hematoxylin&eosin (H&E), Periodic acid-Schiff (PAS)+Hematoxylin (PAS+H) and Masson’s trichrome stains. Pathological changes were scored and statistically evaluated. Results: Compared to the control group, there was a decrease in hemorrhage, vascular congestion, follicular degeneration, inflammation, interstitial edema, vasodilation and growing follicle numbers in all groups; these changes were severe in the G2 group; Mild to moderate severity was observed in the G3, G4 and G5 groups. Conclusion: Renal I/R damage significantly affects the ovaries histopathologically. MEL, CUR, and MEL+CUR partially preserve the histological structure, but MEL treatment seems to be more effective than CUR treatment.

scholarly journals Deletion of soluble epoxide hydrolase enhances coronary reactive hyperemia in isolated mouse heart: role of oxylipins and PPARγ

2016 ◽  
Vol 311 (4) ◽  
pp. R676-R688 ◽  
Author(s):  
Ahmad Hanif ◽  
Matthew L. Edin ◽  
Darryl C. Zeldin ◽  
Christophe Morisseau ◽  
Mohammed A. Nayeem
Keyword(s):  
Epoxide Hydrolase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Hyperemia ◽  
Soluble Epoxide Hydrolase ◽  
Mouse Heart ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist

The relationship between soluble epoxide hydrolase (sEH) and coronary reactive hyperemia (CRH) response to a brief ischemic insult is not known. Epoxyeicosatrienoic acids (EETs) exert cardioprotective effects in ischemia/reperfusion injury. sEH converts EETs into dihydroxyeicosatrienoic-acids (DHETs). Therefore, we hypothesized that knocking out sEH enhances CRH through modulation of oxylipin profiles, including an increase in EET/DHET ratio. Compared with sEH+/+, sEH−/− mice showed enhanced CRH, including greater repayment volume (RV; 28% higher, P < 0.001) and repayment/debt ratio (32% higher, P < 0.001). Oxylipins from the heart perfusates were analyzed by LC-MS/MS. The 14,15-EET/14,15-DHET ratio was 3.7-fold higher at baseline ( P < 0.001) and 5.6-fold higher post-ischemia ( P < 0.001) in sEH−/− compared with sEH+/+ mice. Likewise, the baseline 9,10- and 12,13-EpOME/DiHOME ratios were 3.2-fold ( P < 0.01) and 3.7-fold ( P < 0.001) higher, respectively in sEH−/− compared with sEH+/+ mice. 13-HODE was also significantly increased at baseline by 71% ( P < 0.01) in sEH−/− vs. sEH+/+ mice. Levels of 5-, 11-, 12-, and 15-hydroxyeicosatetraenoic acids were not significantly different between the two strains ( P > 0.05), but were decreased postischemia in both groups ( P = 0.02, P = 0.04, P = 0.05, P = 0.03, respectively). Modulation of CRH by peroxisome proliferator-activated receptor gamma (PPARγ) was demonstrated using a PPARγ-antagonist (T0070907), which reduced repayment volume by 25% in sEH+/+ ( P < 0.001) and 33% in sEH−/− mice ( P < 0.01), and a PPARγ-agonist (rosiglitazone), which increased repayment volume by 37% in both sEH+/+ ( P = 0.04) and sEH−/− mice ( P = 0.04). l-NAME attenuated CRH in both sEH−/− and sEH+/+. These data demonstrate that genetic deletion of sEH resulted in an altered oxylipin profile, which may have led to an enhanced CRH response.

scholarly journals Gastrin Attenuates Renal Ischemia/Reperfusion Injury by a PI3K/Akt/Bad-Mediated Anti-apoptosis Signaling

2020 ◽  
Vol 11 ◽  
Author(s):  
Chao Liu ◽  
Ken Chen ◽  
Huaixiang Wang ◽  
Ye Zhang ◽  
Xudong Duan ◽  
...  
Keyword(s):  
Protective Effect ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Periodic Acid ◽  
Drug Candidate ◽  
Gastrointestinal Hormone ◽  
Akt Inhibitor ◽  
Periodic Acid Schiff

Ischemic/reperfusion (I/R) injury is the primary cause of acute kidney injury (AKI). Gastrin, a gastrointestinal hormone, is involved in the regulation of kidney function of sodium excretion. However, whether gastrin has an effect on kidney I/R injury is unknown. Here we show that cholecystokinin B receptor (CCKBR), the gastrin receptor, was significantly up-regulated in I/R-injured mouse kidneys. While pre-administration of gastrin ameliorated I/R-induced renal pathological damage, as reflected by the levels of serum creatinine and blood urea nitrogen, hematoxylin and eosin staining and periodic acid-Schiff staining. The protective effect could be ascribed to the reduced apoptosis for gastrin reduced tubular cell apoptosis both in vivo and in vitro. In vitro studies also showed gastrin preserved the viability of hypoxia/reoxygenation (H/R)-treated human kidney 2 (HK-2) cells and reduced the lactate dehydrogenase release, which were blocked by CI-988, a specific CCKBR antagonist. Mechanistically, the PI3K/Akt/Bad pathway participates in the pathological process, because gastrin treatment increased phosphorylation of PI3K, Akt and Bad. While in the presence of wortmannin (1 μM), a PI3K inhibitor, the gastrin-induced phosphorylation of Akt after H/R treatment was blocked. Additionally, wortmannin and Akt inhibitor VIII blocked the protective effect of gastrin on viability of HK-2 cells subjected to H/R treatment. These studies reveals that gastrin attenuates kidney I/R injury via a PI3K/Akt/Bad-mediated anti-apoptosis signaling. Thus, gastrin can be considered as a promising drug candidate to prevent AKI.

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