Therapeutic effects of bone marrow mesenchymal stem cells via modulation of TLR2 and TLR4 on renal ischemia-reperfusion injury in male Sprague-Dawley rats

Karimi, Zeinab; Janfeshan, Sahar; Abarghouei, Elias Kargar; Hashemi, Seyedeh‐Sara

doi:10.34172/bi.2021.31

Cited by 6 publications

(3 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Renal I/R injury caused histological and functional alterations in renal and heart tissues. 30 - 32 We also found that tissue damages were associated with high plasma levels of renal and cardiac injury biomarkers, such as BUN, Cr, LDH, and troponin I.…”

Section: Discussionmentioning

confidence: 76%

Protective effects of limb remote ischemic per-conditioning on the heart injury induced by renal ischemic-reperfusion through the interaction of the apelin with the RAS/iNOS pathway

Janfeshan¹,

Masjedi²,

Karimi³

2023

Bioimpacts

Self Cite

View full text Add to dashboard Cite

Introduction: Remote ischemic conditioning upregulates endogenous protective pathways in response to ischemia-reperfusion injury. This study tested the hypothesis that limb remote ischemic per-conditioning (RIPerC) exerts cardioprotective effects via the renin-angiotensin system (RAS)/inducible nitric oxide synthase (iNOS)/apelin pathway. Methods: Renal ischemia-reperfusion injury (I/R) was induced by bilateral occlusion of the renal pellicles for 60 minutes, followed by 24 hours of reperfusion; sham-operated rats served as controls. RIPerC was induced by four cycles (5 minutes) of limb ischemia-reperfusion along with bilateral renal ischemia. The functional disturbance was evaluated by renal (BUN and creatinine) and cardiac (troponin I and lactate dehydrogenase) injury biomarkers. Results: Renal I/R injury increased renal and cardiac injury biomarkers that were reduced in the RIPerC group. Histopathological findings of the kidney and heart were also suggestive of amelioration injury-induced changes in the RIPerC group. Assessment of cardiac electrophysiology revealed that RIPerC ameliorated the decline in P wave duration without significantly affecting other cardiac electrophysiological changes. Further, renal I/R injury increased the plasma (322.40±34.01 IU/L), renal (8.27±1.10 mIU/mg of Protein), and cardiac (68.28±10.28 mIU/mg of Protein) angiotensin-converting enzyme (ACE) activities in association with elevations in the plasma and urine nitrite (25.47±2.01 & 16.62±3.05 μmol/L) and nitrate (15.47±1.33 & 5.01±0.96 μmol/L) levels; these changes were reversed by RIPerC. Further, renal ischemia-reperfusion injury significantly (P=0.047) decreased the renal (but not cardiac) apelin mRNA expression, while renal and cardiac ACE2 (P<0.05) and iNOS (P=0.043) mRNA expressions were significantly increased compared to the sham group; these effects were largely reversed by RIPerC. Conclusion: Our results indicated that RIPerC protects the heart against renal ischemia-reperfusion injury, likely via interaction of the apelin with the RAS/iNOS pathway.

show abstract

Section: Discussionmentioning

confidence: 76%

Protective effects of limb remote ischemic per-conditioning on the heart injury induced by renal ischemic-reperfusion through the interaction of the apelin with the RAS/iNOS pathway

Janfeshan¹,

Masjedi²,

Karimi³

2023

Bioimpacts

Self Cite

View full text Add to dashboard Cite

show abstract

“…Renal tubular damage was indicated by assessing renal shedding of the brush border, tubular necrosis, exfoliation of the epithelial cells, cast deposition, and vascular congestion as previously described. Briefly, renal tissue lesions were classified from 0 to 5 according to the intensity of damages, 0: no damage, 1: less than 20% damage, 2: 21–40% damage, 3: 41–60% damage, 4: 61–80% damage, and 5: more than 81% damage [ 41 , 42 ].…”

Section: Methodsmentioning

confidence: 99%

Hexarelin alleviates apoptosis on ischemic acute kidney injury via MDM2/p53 pathway

Guan,

Li,

Shen

et al. 2023

Eur J Med Res

View full text Add to dashboard Cite

Introduction Hexarelin exhibits significant protection against organ injury in models of ischemia/reperfusion (I/R)-induced injury (IRI). Nevertheless, the impact of Hexarelin on acute kidney injury (AKI) and its underlying mechanism remains unclear. In this study, we investigated the therapeutic potential of Hexarelin in I/R-induced AKI and elucidated its molecular mechanisms. Methods We assessed the protective effects of Hexarelin through both in vivo and in vitro experiments. In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 μg/kg/d for 7 days before being sacrificed 24 h post-IRI. Subsequently, kidney function, histology, and apoptosis were assessed. In vitro, hypoxia/reoxygenation (H/R)-induced HK-2 cell model was used to investigate the impact of Hexarelin on apoptosis in HK-2 cells. Then, we employed molecular docking using a pharmmapper server and autodock software to identify potential target proteins of Hexarelin. Results In this study, rats subjected to I/R developed severe kidney injury characterized by tubular necrosis, tubular dilatation, increased serum creatinine levels, and cell apoptosis. However, pretreatment with Hexarelin exhibited a protective effect by mitigating post-ischemic kidney pathological changes, improving renal function, and inhibiting apoptosis. This was achieved through the downregulation of conventional apoptosis-related genes, such as Caspase-3, Bax and Bad, and the upregulation of the anti-apoptotic protein Bcl-2. Consistent with the in vivo results, Hexarelin also reduced cell apoptosis in post-H/R HK-2 cells. Furthermore, our analysis using GSEA confirmed the essential role of the apoptosis pathway in I/R-induced AKI. Molecular docking revealed a strong binding affinity between Hexarelin and MDM2, suggesting the potential mechanism of Hexarelin’s anti-apoptosis effect at least partially through its interaction with MDM2, a well-known negative regulator of apoptosis-related protein that of p53. To validate these findings, we evaluated the relative expression of MDM2 and p53 in I/R-induced AKI with or without Hexarelin pre-administration and observed a significant suppression of MDM2 and p53 by Hexarelin in both in vivo and in vitro experiments. Conclusion Collectively, Hexarelin was identified as a promising medication in protecting apoptosis against I/R-induced AKI.

show abstract

“…Pathological changes were quanti ed for acute tubular necrosis, the shedding of the proximal tubular brush border, Bowman's space dilatation, intratubular cast formation, and vascular congestion. Pathological changes were scored as the percentage of tubular and vascular damages as follows: 0 = normal, 1 = 10-20%, 2 = 21-40%, 3 = 41-60%, 4 = 61-80%, and 5 = 81-100% (17).…”

Section: Histological Analysismentioning

confidence: 99%

Klotho plays a role in reno protective effect of allopurinol on renal ischemia-reperfusion injury

Karimi,

Ghahramani,

Masjedi

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Allopurinol, a xanthine oxidase inhibitor, recovers histological alterations and renal dysfunction induced during renal ischemic-reperfusion injury. This study investigated the cross-talk between the allopurinol and soluble klotho. Method and material: Rats were randomly divided into three equal groups (n = 8 per group): The sham-operated group without renal ischemia, the BIR (bilateral ischemia-reperfusion) group which underwent renal ischemia, and the BIR + Allo (allopurinol) group which was pretreated with allopurinol (100 mg/kg- gavage) 30 min before BIR. After recovery from the anesthesia, all animals were placed in metabolic cages to collect their urine in 24h. After 24 h, plasma was extracted from a blood sample, which was taken from the tail vein. Plasma and urine samples were saved at -20oC. Kidneys were harvested and weighed. The left kidney was dropped in the buffer of 10% formalin for H&E staining, and the right kidney was located in liquid nitrogen and saved at 80oC for the oxidative stress analysis. Results: After renal ischemia–reperfusion, serum creatinine, blood urea nitrogen, xanthine oxidase, and total oxidative stress levels significantly increased. However, plasma klotho level and total antioxidative capacity decreased in the BIR group. There was a reverse correlation between klotho and xanthine oxidase levels. The pretreatment with allopurinol increased plasma Klotho and induced a protective effect on renal histopathological changes and corrected functional biomarkers. Conclusion: Our result showed that allopurinol enhanced its antioxidative effect by increasing klotho activity. Therefore, Klotho may be involved in the protective effects of allopurinol on the renal injury induced by BIR.

show abstract

Therapeutic effects of bone marrow mesenchymal stem cells via modulation of TLR2 and TLR4 on renal ischemia-reperfusion injury in male Sprague-Dawley rats

Cited by 6 publications

References 48 publications

Protective effects of limb remote ischemic per-conditioning on the heart injury induced by renal ischemic-reperfusion through the interaction of the apelin with the RAS/iNOS pathway

Protective effects of limb remote ischemic per-conditioning on the heart injury induced by renal ischemic-reperfusion through the interaction of the apelin with the RAS/iNOS pathway

Hexarelin alleviates apoptosis on ischemic acute kidney injury via MDM2/p53 pathway

Klotho plays a role in reno protective effect of allopurinol on renal ischemia-reperfusion injury

Contact Info

Product

Resources

About