Oil-In-Water Microemulsion Encapsulation of Antagonist Drugs Prevents Renal Ischemia-Reperfusion Injury in Rats

Developing new therapeutic drugs to prevent ischemia/reperfusion (I/R)-induced renal injuries is highly pursued. Liposomal encapsulation of spironolactone (SP) as a mineralocorticoid antagonist increases dissolution rate, bioavailability and prevents the drug from degradation. In this context, this work develops a new formulation of oil-in-water type microemulsions to enhance the bioavailability of SP. The size of the SP-loaded microemulsion was about 6.0 nm by dynamic light scattering analysis. Briefly, we investigated the effects of nano-encapsulated SP (NESP) on renal oxidative stress, biochemical markers and histopathological changes in a rat model of renal I/R injury. Forty eight male Wistar rats were divided into six groups. Two groups served as control and injury model (I/R). Two groups received “conventional” SP administration (20 mg/kg) and NESP (20 mg/kg), respectively, for two days. The remaining two groups received SP (20 mg/kg) and NESP (20 mg/kg) two days before induction of I/R. At the end of the experiments, serum and kidneys of rats underwent biochemical, molecular and histological examinations. Our results showed that I/R induces renal oxidative stress, abnormal histological features and altered levels of renal biomarkers. Administration of SP in healthy animals did not cause any significant changes in the measured biochemical and histological parameters compared to the control group. However, SP administration in the I/R group caused some corrections in renal injury, although it could not completely restore I/R-induced renal oxidative stress and kidney damage. On the contrary, NESP administration restored kidney oxidative injury via decreasing renal lipid peroxidation and enhancing glutathione, superoxide dismutase and catalase in kidneys of the I/R group. The deviated serum levels of urea, creatinine, total proteins and uric acid were also normalized by NESP administration. Furthermore, NESP protected against renal abnormal histology features induced by I/R. Therefore, NESP has beneficial effects in preventing kidney damage and renal oxidative stress in a rat model of I/R, which deserves further evaluations in the future.

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Glutathione ameliorates liver markers, oxidative stress and inflammatory indices in rats with renal ischemia reperfusion injury

Journal of Renal Injury Prevention ◽

10.15171/jrip.2019.18 ◽

2018 ◽

Vol 8 (2) ◽

pp. 91-97 ◽

Cited By ~ 3

Author(s):

Hassan Ahmadvand ◽

Esmaeel Babaeenezhad ◽

Maryam Nasri ◽

Leila Jafaripour ◽

Reza Mohammadrezaei Khorramabadi

Keyword(s):

Oxidative Stress ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Serum Levels ◽

Renal Ischemia ◽

Paraoxonase 1 ◽

Pon1 Activity ◽

Control Group ◽

Group I ◽

Liver Markers

Introduction: Glutathione (GSH) protects the tissue and cell from oxidative injury. Objectives: In the current study, we investigated the possible effects of GSH on liver markers, oxidative stress and inflammatory indices in rat with renal ischemia reperfusion (RIR) injury. Materials and Methods: Twenty-four adult male Wistar rats were divided into 3 groups (n=8). Group I (the control group), group II (the RIR group) received saline (0.25 mL/d, intraperitoneally; i.p.), group III as the RIR group that received GSH (100 mg/kg/d, i.p.). The treatment with saline or GSH began daily 14 days before RIR induction. RIR was induced by clamping renal pedicles for 45 minutes and 24 hours of reperfusion. Results: RIR significantly increased the serum level of nitric oxide (NO), the serum activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), the serum and renal levels of malondialdehyde (MDA), and the serum activity of myeloperoxidase (MPO). However, RIR significantly decreased the serum and renal levels of GSH, serum paraoxonase 1 (PON1) activity, and the serum and renal activities of catalase (CAT) and glutathione peroxidase (GPX). GSH administration could significantly improve the serum activities of AST, GGT, MPO, GPX and PON1 and serum levels of NO, renal MDA, GSH levels, and serum and also renal CAT activities. Conclusion: Our study indicated that GSH administration ameliorated RIR injury in rats by improving the activities of liver markers and antioxidant enzymes, the levels of MDA, NO, GSH and MPO activity.

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Selenium effects on antioxidant and inflammatory indices in renal ischemia-reperfusion injury in rats

Journal of Renal Injury Prevention ◽

10.15171/jrip.2019.14 ◽

2018 ◽

Vol 8 (2) ◽

pp. 71-77 ◽

Cited By ~ 2

Author(s):

Hassan Ahmadvand ◽

Esmaeel Babaeenezhad ◽

Hashem Nayeri ◽

Zahra Zarei Nezhad

Keyword(s):

Oxidative Stress ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Left Kidney ◽

Serum Levels ◽

Renal Ischemia ◽

Paraoxonase 1 ◽

Control Group ◽

Protective Effects ◽

Oxidative Stress Biomarkers

Introduction: Selenium (Se) is an antioxidant and reactive oxygen species (ROS) scavenger. Objectives: This study was conducted to evaluate the effects of Se on renal functional parameters, oxidative stress biomarkers, myeloperoxidase (MPO) activity, and the nitric oxide (NO) level in renal ischemia-reperfusion (IR) injury in rats. Materials and Methods: Twenty-four male Wistar rats (180–200 g) were selected and subsequently divided into three groups (n=8); group 1 as the control group, group 2 as the untreated group (IR without treatment) and group 3 as the IR group (treated with Se (1 mg/kg/d, intraperitoneally). The period of Se administration was 2 weeks before the inducing renal IR. To cause renal IR, renal pedicles were occluded by safe clamps for 45 minutes. Then, the clamps were removed and 24 hours was considered as reperfusion. After the study, blood sampling from the hearts and the removal of the left kidney was conducted immediately for biochemical measurements. Results: Renal IR significantly increased serum levels of urea, creatinine (Cr), serum and renal malondialdehyde (MDA) levels, serum NO level, and MPO activity. It significantly decreased serum and renal glutathione (GSH) levels, serum paraoxonase 1 activity, serum and renal activities of catalase (CAT), and glutathione peroxidase (GPx). Se could reverse these findings, but the increase of paraoxonase 1 activity and the decrease of MPO activity in IR animals were not significant. Conclusion: It seems that Se has protective effects on inflammatory indices. It can ameliorate renal IR complications which are associated with oxidative stress and inflammation.

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Antioxidative and anti-inflammatory impact of valsartan against renal ischemia-reperfusion injury; role of nitric oxide signaling pathway

Immunopathologia Persa ◽

10.15171/ipp.2019.19 ◽

2019 ◽

Vol 5 (2) ◽

pp. e19-e19

Author(s):

Leila Mohmoodnia ◽

Sarina Safari Ahmadvand ◽

Sahar Koushki ◽

Behrooz Farzan ◽

Sajad Papi ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Serum Levels ◽

Renal Ischemia ◽

Control Group ◽

Type I ◽

Angiotensin Receptor ◽

Renal Ischemia Reperfusion Injury ◽

Control Group Group

Introduction: Renal ischemia reperfusion injury is one of the main causes of acute renal failure, which is associated with high mortality. Tissue damage caused by ischemia-reperfusion occurs due to the release of oxygen free radicals. Type I angiotensin receptor antagonists such as valsartan can be useful in the treatment of chronic kidney disease and hypertension. Objectives: We aimed to evaluate the protective effect of valsartan against renal ischemia reperfusion via antioxidant property and nitric oxide (NO) signaling pathway. Materials and Methods: Fifty male Wistar rats (220±10 g) were randomly divided into five groups as follows: Group 1; healthy rats without ischemia-reperfusion (control group). Group 2; rats with ischemia reperfusion (IR) (IR control group). Group 3; rats with IR which received 30 mg/kg valsartan orally. Group 4; rats with IR which received 30 mg/kg valsartan together with 40 mg/kg L-NAME. Group 5; rats with IR which received 30 mg/kg valsartan together with 40 mg/kg L-arginine. To induce ischemia-reperfusion, rats were anesthetized with thiopental and underwent surgery. Then, we induced ischemia with blocking blood vessels for 45 minutes by clamping. Biochemical parameters including urea and creatinine were measured using commercial kits. Oxidative stress and inflammatory parameters were measured by ELISA method. Renal tissues were stained with hematoxylin and eosin. Finally, the Kolmogorov-Smirnov test was used to determine the normal distribution of data. Results: The findings of this study indicated that treatment with valsartan and valsartan plus L-arginine leads to significant decrease in the serum levels of creatinine, urea, and albumin/creatinine, malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in contrast to IR control group which has increased level of these parameters. On the other hand, treatment with valsartan and valsartan plus L-arginine lead to increase in the serum levels of glutathione peroxidase (GPX), in contrast to ischemia reperfusion control group. Conclusion: Our data revealed that valsartan as a type I angiotensin receptor antagonist could decrease oxidative stress and inflammation due to renal ischemia reperfusion injury. Hence, valsartan could propose as a therapeutic agent for kidney diseases such as renal ischemia-reperfusion injury regarded to these renoprotective effects.

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Ascorbic acid improves renal microcirculatory oxygenation in a rat model of renal I/R injury

Journal of Translational Internal Medicine ◽

10.1515/jtim-2015-0011 ◽

2015 ◽

Vol 3 (3) ◽

pp. 116-125 ◽

Cited By ~ 3

Author(s):

Bulent Ergin ◽

Coert J. Zuurbier ◽

Rick Bezemer ◽

Asli Kandil ◽

Emre Almac ◽

...

Keyword(s):

Oxidative Stress ◽

Ascorbic Acid ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Renal Tissue ◽

Control Group ◽

Free Oxygen Radicals ◽

Time Control ◽

Inflammatory Parameters

AbstractBackground and objectives: Acute kidney injury (AKI) is a clinical condition associated with a degree of morbidity and mortality despite supportive care, and ischemia/reperfusion injury (I/R) is one of the main causes of AKI. The pathophysiology of I/R injury is a complex cascade of events including the release of free oxygen radicals followed by damage to proteins, lipids, mitochondria, and deranged tissue oxygenation. In this study, we investigated whether the antioxidant ascorbic acid would be able to largely prevent oxidative stress and consequently, reduce I/R-related injury to the kidneys in terms of oxygenation, inflammation, and renal failure. Materials and methods: Rats were divided into three groups (n = 6/group): (1) a time control group; (2) a group subjected to renal ischemia for 60 min by high aortic occlusion followed by 2 h of reperfusion (I/R); and (3) a group subjected to I/R and treated with an i.v. 100 mg/kg bolus ascorbic acid 15 min before ischemia and continuous infusion of 50 mg/kg/hour for 2 h during reperfusion (I/R + AA). We measured renal tissue oxidative stress, microvascular oxygenation, renal oxygen delivery and consumption, and renal expression of inflammatory and injury markers. Results: We demonstrated that aortic clamping and release resulted in increased oxidative stress and inflammation that was associated with a significant fall in systemic and renal hemodynamics and oxygenation parameters. The treatment of ascorbic acid completely abrogated oxidative stress and inflammatory parameters. However, it only partly improved microcirculatory oxygenation and was without any effect on anuria. Conclusion: The ascorbic acid treatment partly improves microcirculatory oxygenation and prevents oxidative stress without restoring urine output in a severe I/R model of AKI.

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Bolus Administration of Polyamines Boosts Effects on Hepatic Ischemia-Reperfusion Injury and Regeneration in Rats

European Surgical Research ◽

10.1159/000497434 ◽

2019 ◽

Vol 60 (1-2) ◽

pp. 63-73

Author(s):

Junshi Doi ◽

Yasuhiro Fujimoto ◽

Takumi Teratani ◽

Naoya Kasahara ◽

Masashi Maeda ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Liver Weight ◽

Serum Levels ◽

Chow Group ◽

Control Group ◽

Bolus Administration ◽

Remnant Liver ◽

Blood Concentrations

Background:It was demonstrated that polyamines ameliorate ischemia-reperfusion injury (IRI) and promote regeneration in the liver. An optimal protocol of polyamine treatment remains unknown in the clinical setting. We examined 2 types of administration methods using rat models. Methods: Experiment 1: evaluation of pharmacokinetics of polyamines. Experiment 2: for 3 days preoperatively and 5 days postoperatively, polyamines were given to male Lewis rats in the following three groups: the control group, no polyamine administration; the chow group, 0.05% polyamines mixed in chow; the bolus group, polyamines (200 μmol/kg) given by gastric tube once a day. All rats received 70% hepatectomy after 40 min of warm IRI. Postoperatively, IRI and regeneration were evaluated with assessment of serum levels of hepatic enzymes, histology and immunohistochemistry of liver tissue, and measurement of remnant liver weight. Results: The blood concentrations of polyamines in the portal vein increased at 1 h of bolus administration, while they did not increase without the bolus. The bolus group was significantly associated with lower serum levels of aspartate/alanine aminotransferases (p < 0.05), decreased hepatocyte congestion, vacuolization and necrosis in histopathological scoring (p < 0.05), a lower number of TUNEL-positive hepatocytes (p < 0.05), higher remnant liver weight at 24, 48, and 168 h (p < 0.05), and a higher Ki-67 labeling index (24 h, p < 0.01) compared with the chow group. Conclusion: The bolus administration of polyamines was more effective in ameliorating IRI and promoting regeneration than chow administration. Perioperative bolus administration of polyamines might be an optimal treatment, when clinically applied.

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Corrigendum: Effect of aminoguanidine on sciatic functional index, oxidative stress, and rate of apoptosis in an experimental rat model of ischemia–reperfusion injury

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2014-0484 ◽

2015 ◽

Vol 93 (4) ◽

pp. 309-309 ◽

Cited By ~ 1

Author(s):

Mohsen Alipour ◽

Farhad Ghadiri-Soufi ◽

Mohammad-Reza Jafari

Keyword(s):

Oxidative Stress ◽

Reperfusion Injury ◽

Rat Model ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Functional Index ◽

Experimental Rat Model ◽

Sciatic Functional Index

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Effects of Cilostazol and Diltiazem Hydrochloride on Ischemia-Reperfusion Injury in a Rat Hindlimb Model

The Heart Surgery Forum ◽

10.1532/hsf.1663 ◽

2017 ◽

Vol 20 (2) ◽

pp. 058 ◽

Cited By ~ 2

Author(s):

Bekir İNAN ◽

Selma SÖNMEZ ERGÜN ◽

Asiye NURTEN ◽

Canan KÜÇÜKGERGİN ◽

Aslı ZENGİN TÜRKMEN ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Saline Group ◽

Dimethyl Sulphoxide ◽

Control Group ◽

Albino Rats ◽

Diltiazem Hydrochloride ◽

Beneficial Effects ◽

Group I

Objective: Free radicals and neutrophils are potent sources of ischemia-reperfusion injury (I/R) and they can be limited by the use of exogenous application of some therapeutic agents. The objective of this study was to compare the effects of cilostazol and diltiazem hydrochloride in a rat hind limb model of I/R injury. Methods: Skeletal muscles submitted to 2 hours of ischemia by placing an aneurysm clip to femoral artery and reperfused after 1, 2 and 4 hours. Seventy-two Wistar-Albino rats were randomly divided into mainly four groups according to treatment agents: Group I (control group) was treated with saline; Group II was treated with diltiazem hydrochloride; Group III was treated with cilostazol in 30% dimethyl sulphoxide; and Group IV was treated with 30% dimethyl sulphoxide intraperitoneally. These four main groups also subdivided into three subgroups according to duration of the reperfusion times. Blood samples were taken and all rats were sacrificed. Results: Cilostazol-treated groups demonstrated a significant decrease in tissue and serum malondialdehyde (MDA) levels, and tissue myeloperoxidase (MPO ) activity compared with other groups. Increase in serum nitric oxide (NOx) level was significantly higher in all subgroups of cilastazol, diltiazem hydrochloride, and dimethyl sulphoxide groups versus the control group.Conclusion: Although these results suggest the beneficial effects of cilostazol and diltiazem hydrochloride on I/R injury, the effect of cilostazol on I/R injury seems to be more efficient than diltiazem hydrochloride.

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The long-term protective effect of tadalafil on spermatogenesis following testicular ischemia-reperfusion injury in a rat model

10.21203/rs.3.rs-79465/v1 ◽

2020 ◽

Author(s):

Bomi Kim ◽

EunHye Lee ◽

BoHyun Yoon ◽

So Young Chun ◽

Jae-Wook Chung ◽

...

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Reperfusion Injury ◽

Rat Model ◽

Testicular Torsion ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Group A ◽

Testicular Ischemia

Abstract Background Testicular torsion is a urological emergency in which misdiagnosis and inappropriate treatment can lead to testicular atrophy and male infertility owing to ischemia-reperfusion injury (IRI). Although experimental studies of testicular torsion have been preceded, promising therapeutic agents based on the long-term effect for spermatogenesis have not been identified in testicular ischemia reperfusion injury (IRI) animal model. Tadalafil, one of the phosphodiesterase-5 inhibitors commonly used in the treatment of erectile dysfunction, has recently reported a protective effect against IRI in several organs. In this study, we evaluated the long-term protective effect of tadalafil for spermatogenesis in a rat testicular IRI model. Methods Forty-eight adolescent Sprague–Dawley rats were divided into 6 groups (A-F). Sham operation was performed in group A. Group B received surgical 720-degree torsion of the left testis without any medication. Groups C, D, E, and F were operated surgical torsion with tadalafil at varying doses (0.3 mg/kg, 1.0 mg/kg) and durations (single or daily administration for 4 weeks). Detorsion was performed after 3 hour of torsion in all rats except the sham group. Four weeks after operation, both testes were evaluated of spermatogenesis using Johnsen scoring. To evaluate the protective effect of tadalafil against oxidative stress by IRI, malondialdehyde (MDA) and superoxide dismutase (SOD) level were analyzed via ELISA in both testes 4 hour after detorsion in the same experiments as in group A, B, and C. Results For the evaluation of spermatogenesis according to doses, the groups with high-dose tadalafil showed a higher Johnsen scores than low-dose counterparts. The groups with daily administration for 4weeks were observed a higher Johnsen scores than those given a single administration. Furthermore, molecular markers (MDA and SOD) related with oxidative stress and histopathologic findings showed remarkable improvement after tadalafil administration. Conclusion Tadalafil alleviated long-term deterioration of spermatogenesis and oxidative stress by restoring antioxidant status after testicular IRI rat model. Furthermore, it demonstrated a protective effect against testicular IRI in a time- and dose-dependent manner.

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