Protective effects of saffron (its active constituent, crocin) on nephropathy in streptozotocin-induced diabetic rats

2014 ◽  
Vol 34 (2) ◽  
pp. 127-134 ◽  
Author(s):  
E Altinoz ◽  
Z Oner ◽  
H Elbe ◽  
Y Cigremis ◽  
Y Turkoz

The reactive oxygen species take role in pathogenesis of many diseases including hypoxia, hypercholesterolemia, atherosclerosis, nephropathy, hypertension, ischemia–reperfusion damage, and heart defects. The aim of this study was to evaluate whether crocin administration could protect kidney injury from oxidative stress in streptozotocin-induced diabetic rats. The rats were randomly divided into 3 groups each containing 10 animals as follows: group 1, control group; group 2, diabetes mellitus (DM) group; and group 3, DM + crocin group. At the end of the study, trunk blood was collected to determine the plasma levels of blood urea nitrogen (BUN) and creatinine (Cr). The kidney tissue was removed, and biochemical and histological changes were examined. Diabetes caused a significant increase in malondialdehyde (MDA) and xanthine oxidase (XO) activities and a decrease in glutathione (GSH) contents (  p < 0.01) when compared with control group in the rat kidneys. Crocin given to DM rats significantly decreased MDA (  p < 0.01) and XO (  p < 0.05) activities and elevated GSH (  p < 0.05) contents when compared with DM group. Plasma levels of BUN and Cr were significantly higher in the DM group when compared with the control group (  p < 0.01). Pretreatment of the DM animals with crocin decreased the high level of serum Cr and BUN. Control group was normal in histological appearance, but congestion, severe inflammation, tubular desquamation, tubular necrosis, and hydropic degeneration in tubular cells were observed in the DM group. Histopathological changes markedly reduced, and appearance of kidney was nearly similar to control group in DM + crocin group. Our results show that crocin could be beneficial in reducing diabetes-induced renal injury.

2021 ◽  
Author(s):  
Mohammad Amin Mombeini ◽  
Hadi Kalantar ◽  
Elahe Sadeghi ◽  
Mehdi Goudarzi ◽  
Hamidreza Khalili ◽  
...  

Abstract Purpose Cyclophosphamide is an alkylating agent with nephrotoxicity that constraints its clinical application. Berberine is an isoquinoline derivative alkaloid with biological functions like antioxidant and anti-inflammatory. The current research intended to examine the nephroprotective impacts of berberine against cyclophosphamide-stimulated nephrotoxicity. Methods Forty animal subjects were randomly separated into five categories of control (Group I). Cyclophosphamide (200 mg/kg, i.p., on 7th day) (Group II), and groups III and IV that received berberine 50 and 100 mg/kg orally for seven days and a single injection of cyclophosphamide on 7th day. Group V as berberine (100 mg/kg, alone). On day 8, blood samples were drawn from the retro-orbital sinus to determine serum levels of blood urea nitrogen (BUN), creatinine (Cr), Neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) as biomarkers for kidney injury. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities as oxidative stress factors, tumor necrosis factor- α (TNF-α) and interleukin 1 beta (IL-1β) levels as inflammatory mediators were assessed in kidney tissue. Results The results of this study demonstrated that berberine was able to protect remarkably the kidney from CP-induced injury through decreasing the level of BUN, Cr, NGAL, KIM-1, NO, MDA TNF-α, IL-1β and increasing the level of GSH, CAT, SOD and GPx activities. Conclusion Berberine may be employed as a natural agent to prevent cyclophosphamide-induced nephrotoxicity through anti-oxidant and anti-inflammatory effects.


2018 ◽  
Vol 127 (05) ◽  
pp. 320-325 ◽  
Author(s):  
Fatemeh Ramezani-Aliakbari ◽  
Mohammad Badavi ◽  
Mahin Dianat ◽  
Seyed Mard ◽  
Akram Ahangarpour

AbstractTrimetazidine (TMZ), as an anti-ischemic drug, plays a critical role in protecting against cardiovascular complications induced by diabetes. This study was therefore aimed to evaluate the protective effects of TMZ on reperfusion-induced arrhythmias in the diabetic rats. Male Sprague-Dawley rats (250±20 g) were randomly assigned to four (n=8): control rats (C), alloxan induced diabetic rats (D), diabetic rats treated with TMZ (10 mg/kg, D+T10), diabetic rats treated with TMZ (30 mg/kg, D+T30). TMZ was treated orally once daily for 8 weeks. Diabetes was induced by a single intraperitoneal injection of alloxan (120 mg/kg). Ischemia-reperfusion (I/R) was carried out via 30 min of ischemia and following120-min reperfusion. The magnitude and score of arrhythmia, the left ventricular function, infarct size, lactate dehydrogenase (LDH), myocardial creatine kinase (CK-MB) and troponin (cTnI) were measured. The findings were evaluated by two-way repeated measures and one-way ANOVA followed by LSD post hoc test and Fisher's exact test for incidence percentage. The duration, incidence and score of arrhythmia (p<0.001), infarct size (p<0.01) were significantly increased, the cardiac contractility (±dp/dt), LDH, CK-MB (p<0.001) and cTnI (p<0.05) were significantly decreased in the diabetic rats in comparison with the control group. However, treatment with TMZ in the diabetic rats was significantly improved the duration (p<0.001), incidence and score of arrhythmia,±dp/dt LDH, CK-MB, cTnI (p<0.05) and infarct size (p<0.01) in comparison with the untreated diabetic group. The present study indicates anti-arrhythmic effect of TMZ in reducing arrhythmias induced by reperfusion in the diabetic rats.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Milan Ivanov ◽  
Zoran Miloradovic ◽  
Nevena Mihailovic-Stanojevic ◽  
Djurdjica Jovovic ◽  
Danijela Karanovic ◽  
...  

Abstract Background and Aims Renal ischemia–reperfusion (RIR) injury is one of the factors in the development of acute kidney injury (AKI). AKI is multifactorially caused, but the mechanism of pathogenesis and development of this disease is still incompletely defined. AKI is characterized by the sudden appearance, rapid progression of disease and very uncertain and often fatal outcome. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the breakdown of heme to biliverdin, carbon monoxide, and iron. HO-1 is now recognized as a protection factor in acute kidney injury. The aim of this study was to determine the effect of preconditioning with hyperbaric oxygen (HBO) on HO-1 expression in kidney tissue and kidney function in spontaneously hypertensive rats (SHR) during kidney ischemia–reperfusion injury. Method An experiment was performed in anesthetized, adult six-month-old male SHR. The right kidney was removed and the renal ischemia was performed by clamping the left renal artery for 40 minutes. SHR were randomly selected in three experimental groups: sham operated group (SHAM; n=7); AKI control group (AKI; n=9); and AKI group with HBO (AKI+HBO; n=9). Treated group were placed into experimental HBO chambers and exposed to pure oxygen, twice a day (in a 12 hour period, 8AM and 8 PM) for two consecutive days in the following manner: 10 minutes slow compression, 2.026 bar for 60 minutes, 10 minutes slow decompression. Mean arterial pressure (MAP) and HO-1 expression in kidney tissue were measured 24h after reperfusion. Clearance of creatinine (CCr), urea (CUr) and phosphate (CPh) were calculated 24h after reperfusion. Results After AKI induction reduction of blood pressure was recorded in both groups with AKI. Preconditioning with HBO significantly improved kidney function in rats with AKI compared to control group. HO-1 expression in kidney tissue was significantly higher in the treated group (p&lt;0,01) compared to SHAM and AKI control group. Conclusion Our results suggest that HBO treatment improves kidney function in the AKI+HBO vs. AKI control group. This implies that increased level of HO-1 due to preconditioning with hyperbaric oxygen may have beneficial effects on kidney function, and potentially protective effect in an ischemic model of AKI with hypertension.


2020 ◽  
Vol 24 (3) ◽  
Author(s):  
Seyfi Kartal ◽  
Gülay Kip ◽  
Ayşegül Küçük ◽  
Ali Atan ◽  
Özlem Erdem ◽  
...  

Ischemia-reperfusion injury is a complex, which causes cell damage. In this study, we aimed to investigate the protective effects of dexmedetomidine on lung in the renal IR model in diabetic rats. After approval of the ethics committee, diabetes was induced by streptozocin (55 mg/kg) and then 24 Wistar Albino rats were randomly divided into 4 groups. Diabetic control group (group DC), diabetic dexmedetomidine (group DD), diabetic ischemia-reperfusion (group DIR), diabetic ischemia-reperfusion - dexmedetomidine (group DIR-D).


Author(s):  
Bassim I Mohammed ◽  
Najah R Hadi ◽  
Jabber Huda ◽  
Galal Elkilany ◽  
RB Singh

Renal ischemia-reperfusion (Renal I/R) leads to acute kidney injury (AKI),a major kidney disease associated with an increasing prevalence and high mortality rates. A variety of experimental models,both in vitro and in vivo,have been used to study the pathogenic mechanisms of ischemic AKI and to test reno-protective strategies. Aim: To study potential protective effects of artesunate on renal I/R injury. Renal I/R injury was unilaterally induced in adult (3 to 5 months) male Sprague-Dawely rats,whose weights ranged from 180 to 390 g. Thereafter,the animals were pre-treated with artesunate intra-peritoneally,and at the end of reperfusion sacrificed humanely. Plasma,serum and tissue samples were obtained for analysis. Plasma concentrations of NGAL (neutrophil gelatinase associated lipocalin),an iron-trafficking protein involved in multiple processes such as apoptosis,innate immunity and renal development,and tissue concentrations of IL-18 (Interleukin-18) were measured via ELISA analysis. Serum urea and creatinine were also measured in the samples. Artesunate improved renal ischemia reperfusion,including renal function and brought about reductions in inflammatory mediators and kidney tissue injury. Plasma concentrations of NGAL and tissue concentrations of IL-18 were significantly (p < 0.05) lower in the artesunatepretreated group than in the vehicle and control groups. Furthermore,serum concentrations of urea and creatinine were significantly (p < 0.05) decreased in the pretreated group as compared to the control group. Artesunate can significantly improve renal function following I/R through down-regulation of inflammatory parameters and NGAL expression. Furthermore,it could serve as a potential therapy in ischemia reperfusion-induced acute kidney injury.


Folia Medica ◽  
2020 ◽  
Vol 62 (1) ◽  
pp. 82-88
Author(s):  
Assel Kudaibergenova ◽  
Nurettin Aydogdu ◽  
Nihayet Kandemir ◽  
Muhammed Ali Aydin

Introduction: Kisspeptin is biologically active peptide encoded by the KISS1 gene that is structurally found in the kidney tubule, collecting duct and vein smooth muscle cells.&nbsp; &nbsp; Aim: We aimed to investigate the role of kisspeptin in kidney function and renal pathophysiology in experimental kidney ischemia/reperfusion (I/R) injury.&nbsp; &nbsp; Materials and methods: Male Spraque-Dawley rats were divided into control and I/R groups (n=8). Both kidney vessels of I/R group rats were clamped and subjected to ischemia for 60 minutes and reperfusion for 48 hours. After the reperfusion period blood samples and kidney tissue were collected under anesthesia.&nbsp; &nbsp; Results: Levels of urea, creatinine (p<0.01) in serum, Kim-1 in urine (p<0.05) were increased, creatinine clearance, aldosterone and ANG II levels in serum were decreased in the I/R group compared with the Control group (p<0.05). Kidney kisspeptin levels decreased and urine kisspeptin levels increased (p<0.05).&nbsp; &nbsp; Conclusions: The present study has shown that the levels of kisspeptin change in kidney damage and thus the kisspeptin may play a role in the regulation of renal function and in the pathophysiology of acute kidney injury.


Drug Research ◽  
2019 ◽  
Vol 69 (11) ◽  
pp. 612-620
Author(s):  
Fatemeh Ahmadi ◽  
Saeed Hajihashemi ◽  
Ali Rahbari ◽  
Fatemeh Ghanbari

Abstract Background Ischemia-reperfusion (I-R) leads to acute kidney injury (AKI). The present study investigated the effects of nitroglycerine (NG) on improving renal dysfunctions caused by I-R in rats. Methodology Twenty-four rats were equally divided into four groups: (1) the control group, (2) the sham group, (3) the I-R group, and (4) NG-treated groups.NG (50 μg/kg) was injected intraperitoneally after induction of IR. I-R was induced through clamping of the bilateral renal artery and vein of both kidneys for 20 min followed by 24 h of reperfusion. Results NG significantly increased the creatinine clearance levels and renal blood flow rate (which was reduced by I-R). NG also significantly improved serum electrolytes (sodium and potassium) that were disordered by I-R. In addition, NG significantly offset impaired antioxidant defense mechanism and inhibited lipid peroxidation. Conclusions The results show NG has a protective effect on renal tissue against AKI caused by I-R. These protective effects mediated through antioxidant activity and decrease of lipid peroxidation.


2021 ◽  
Vol 12 (5) ◽  
pp. 6100-6113

Renal ischemia/reperfusion (I/R) injury contains multiple mechanisms involving an excessive amount of ROS that causes oxidative stress, inflammation, and rapid kidney dysfunction. This work aimed to study the ability of thalixisostere 3f on angiogenesis and antioxidant effect in I/R. There was a significant decrease in VEGF from thalix and modified thalixisostere 3f groups as compared with that of a negative control group (P < 0.001). There was a significant decrease in the mean concentration of MDA in kidney tissue obtained from thalix and thalixisostere 3f groups as compared with that of a positive control group (P < 0.001). There was a significant increase in the mean concentrations of SOD and GSH in kidney tissue of group's thalix and thalixisostere 3f groups as compared with that of a positive control group. We found that thalixisostere 3f is more effective than thalix in inhibiting the expression VEGF as pro-angiogenic factors. Molecular docking study indicated that the proper recognition of the inhibitor thalix-isostere with the conserved amino acid residues at the binding active site of VEGFR2 as one of the important enzymes to be targeted as part of antiangiogenic anticancer.


Acute kidney injury (AKI) resulting from ischemia-reperfusion injury (IRI) is among the most common complications in hospitalized patients. In recent years, it has been argued that exercise is an approach to attenuate impairments caused by AKI. The purpose of this study was to investigate whether eight weeks of resistance training (RT) has protective effects on IRI. Thirty male Wistar rats (210-230 g) were randomly divided into four groups, including RT+ISC (n=7), RT (n=8), ISC (n=7), and sham (n=8). Animals underwent eight weeks of RT, and 48 hours after the last training session, ischemia (45 min) reperfusion (24 h) was induced. Then animals were sacrificed, and blood and kidney tissue samples were collected to measure creatinine (Cr), blood urea nitrogen (BUN), kidney tissue damage score (KTDS), and kidney weight (KW). The results showed that IRI caused a significant increase in Cr, BUN, KTDS, and KW (p-value <0.05), while RT decreased the severity of KTDS, Cr, and BUN remarkably. (p≤0.05). RT, however, did not attenuate KW (p≤0.05). Overall, the findings of our study provide evidence that RT can attenuate IRI-induced AKI considering enhanced biomarkers; However, further research should be conducted to make certain about the protective effects of exercise training, especially RT.


2007 ◽  
Vol 292 (3) ◽  
pp. F1082-F1093 ◽  
Author(s):  
Christophe Jayle ◽  
Frederic Favreau ◽  
Kequiang Zhang ◽  
Carole Doucet ◽  
Jean Michel Goujon ◽  
...  

Acute renal failure (ARF) is often the consequence of an ischemia-reperfusion injury (IRI) and associated with high mortality. Warm ischemia (WI) is a crucial factor of tissue damage, and tissue destruction led by ischemia-reperfusion (I/R) can impact the early and long-term functional outcome. Trimetazidine (TMZ) is an anti-ischemic drug. Previously, we already verified its protective effect on a cold-ischemic pig kidney model by directly adding TMZ into the preservation solution (Faure JP, Baumert H, Han Z, Goujon JM, Favreau F, Dutheil D, Petit I, Barriere M, Tallineau C, Tillement JP, Carretier M, Mauco G, Papadopoulos V, Hauet T. Biochem Pharmacol 66: 2241–2250, 2003; Faure JP, Petit I, Zhang K, Dutheil D, Doucet C, Favreau F, Eugene M, Goujon JM, Tillement JP, Mauco G, Vandewalle A, Hauet T. Am J Transplant 4: 495–504, 2004). In this study, we aimed to study the potential effect of TMZ pretreatment (5 mg/kg iv 24 h before WI) on the injury caused by WI for 45, 60, and 90 min and reperfusion in a WI pig kidney model. Compared with sham-operated (control) and uninephrectomized animals (UNX), TMZ pretreatment significantly reduced deleterious effects after 45 min, and particularly 60 and 90 min, of WI by improving the recovery of renal function and minimizing the inflammatory response commonly prevalent in ischemic kidney injury. Compared with controls (control group and UNX group), it was observed that 1) hypoxia-inducible factor-1 (HIF-1α) expression occurred earlier and with a higher intensity in the TMZ-treated groups; 2) the reduction of IRI during the first week following reperfusion was correlated with an earlier and greater expression of stathmin, which is involved in the process of tubular repair; and 3) the tubulointerstitial fibrosis was reduced, particularly after 60 and 90 min of WI. In conclusion, TMZ made the warm-ischemic kidneys more resistant to the deleterious impact of a single episode of I/R and reduced early and long-term subsequent damage.


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