Bone marrow-derived mesenchymal stem cells modulate apoptosis and angiogenesis in cyclophosphamide-induced spleen injury in rats

dien, Heba M. Saad El; Bakhaat, Gamal Abdelrahman; Rashwan, Eman K.; Alaaeldin, Rania; Fathy, Moustafa

doi:10.21608/ejh.2022.152313.1735

Cited by 3 publications

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“…The ROS generation during IR injury results in the deleterious effects of IR injury on the cell, with subsequent inflammatory response initiation and AKI development [66]. Additionally, the generation of ROS activates the cell death signaling pathways such as apoptosis and necrosis [67,68]. In the present study, GPX and SOD activities were found to be decreased during IR injury, but after azilsartan treatment, they were notably elevated, which suggests the antioxidant activity of azilsartan, which also has been previously observed through the repression of angiotensin and the oxidative stress [40,69].…”

Section: Discussionmentioning

confidence: 99%

Azilsartan Modulates HMGB1/NF-κB/p38/ERK1/2/JNK and Apoptosis Pathways during Renal Ischemia Reperfusion Injury

Alaaeldin

Bakkar

Mohyeldin

et al. 2023

Cells

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Renal ischemia/reperfusion (IR) injury is characterized by an unexpected impairment of blood flow to the kidney. Azilsartan is an angiotensin receptor blocker that is approved for the management of hypertension. The present study aimed to investigate, on molecular basics, the nephroprotective activity of azilsartan on renal IR injury in rats. Rats were assigned into four groups: (1) Sham group, (2) Azilsartan group, (3) IR group, and (4) IR/Azilsartan-treated group. Histological examination and renal function were evaluated. Levels of KIM-1, HMGB1, caspase 3, GPX, SOD, NF-κB, and p53 proteins were investigated using ELISA. mRNA levels of IL-1β, IL6, IL10, TNF-α, NF-κB, p53, and bax were assessed by qRT-PCR. Expression of p38, JNK, and ERK1/2 proteins was investigated by Western blotting. IR injury resulted in tissue damage, elevation of creatinine, BUN, KIM-1, HMGB1, caspase 3, NF-κB, and p53 levels, decreasing GPX and SOD activities, and up-regulation of NF-κB, IL-1β, IL6, TNF-α, p53, and bax genes. Furthermore, it up-regulated the expression of phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Interestingly, treatment of the injured rats with azilsartan significantly alleviated IR injury-induced histopathological and biochemical changes. It reduced the creatinine, BUN, KIM-1, HMGB1, caspase-3, NF-κB, and p53 levels, elevated GPX and SOD activities, down-regulated the expression of NF-κB, IL-1β, IL6, TNF-α, p53, and bax genes, and up-regulated IL10 gene expression. Furthermore, it decreased the phosphorylated/total ratio of p38, ERK1/2, and JNK proteins. Azilsartan exhibited nephroprotective activity in IR-injured rats via its antioxidant effect, suppression of inflammation, attenuation of apoptosis, and inhibition of HMGB1/NF-κB/p38/ERK1/2/JNK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Azilsartan Modulates HMGB1/NF-κB/p38/ERK1/2/JNK and Apoptosis Pathways during Renal Ischemia Reperfusion Injury

Alaaeldin

Bakkar

Mohyeldin

et al. 2023

Cells

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“…These promising findings were in accordance with those that demonstrated that angiotensin receptor blockers control the oxidative stress and apoptosis that are produced by angiotensin II in mesangial cells [ 92 ]. In addition, MSCs could have a direct therapeutic effect by replacing damaged cells or an indirect therapeutic effect by triggering cellular regeneration, as well as stimulate the production of factors with antiapoptotic, anti-inflammatory, mitogenic, or angiogenic activities [ 93 , 94 ].…”

Section: Discussionmentioning

confidence: 99%

Curative Effect of AD-MSCs against Cisplatin-Induced Hepatotoxicity in Rats is Potentiated by Azilsartan: Targeting Oxidative Stress, MAPK, and Apoptosis Signaling Pathways

Bekhit,

Beshay,

Fawzy

et al. 2023

Stem Cells International

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Despite its clinical value, cisplatin (CISP) is complicated by marked hepatotoxicity via inducing oxidative stress, inflammatory, and apoptotic pathways. This study aims to explore the protective impact of azilsartan (AZIL), an antihypertensive drug, in addition to adipose tissue-derived mesenchymal stem cells (AD-MSCs) on CISP-induced hepatotoxicity. After characterization and labeling of AD-MSCs by PKH26 dye, 54 Wistar male albino rats were randomly divided into nine groups: I (CONT), II (AZIL.H), III (CISP), IV (CISP + AZIL.L), V (CISP + AZIL.H), VI (CISP + AD-MSCs), VII (CISP + AZIL.L + AD-MSCs), VIII (CISP + AZIL.H + AD-MSCs), and IX (CISP + VITA C). Serum alanine aminotransferase (ALT), alanine aminotransferase (AST), and albumin levels were determined. Assessment of reactive oxygen species, malondialdehyde, and glutathione contents, and superoxide dismutase activity and histopathological evaluations were done on hepatic tissue. Quantitative real-time PCR was utilized to estimate the expression of TNF-α and IL-6 genes. Cell homing of labeled AD-MSCs to the liver tissues was investigated. Hepatic expression of JNK1/2, ERK1/2, p38, Bax, Bcl-2, and cleaved caspase-3 proteins was investigated by western blot analysis. CISP elevated serum ALT and AST activities, reduced albumin level, and remarkably changed the hepatic architecture. It increased the expression TNF-α and IL-6 genes, raised the expression of JNK1/2, ERK1/2, p38, Bax, and cleaved caspase-3 proteins, and diminished the Bcl-2 protein. By contrast, treatment of animals with either AZIL or AD-MSCs dramatically reduced the effects of CISP injection. Moreover, treatment with combination therapy (AZIL.L or H + AD-MSCs) considerably mitigated all previously mentioned alterations superior to AZIL or AD-MSCs alone, which might be attributed to the AZIL-enhanced homing ability of AD-MSCs into the injured liver tissue. In conclusion, the present findings demonstrated that AZIL improves the hepatoprotective potential of AD-MSCs against CISP-induced hepatotoxicity by modulating oxidative stress, mitogen-activated protein kinase, and apoptotic pathways.

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“…After ten days animals were sacrificed, lung tissue was obtained and processed for light microscopy exam, and samples were taken to -80 for RNA extraction [18] .…”

Section: Experimental Model and Treatment Protocolsmentioning

confidence: 99%

The potential ameliorative effect of Bone marrow Derived Mesenchymal Stem Cells on Cyclophosphamide Injured Lung in Adult Female Albino Rats

Jaber

dien

Tawfeek

2023

Egyptian Journal of Histology

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Background: Mesenchymal stem cells particularly those derived from bone marrow (BM-MSCs) exhibit self-renewal as well as trilineage differentiation capabilities. These cells are considered for cell therapy in several medical disorders. Cyclophosphamide is a well-known immunosuppressive drug, it has a potential pulmonary damage effect in humans and animals. Therefore, the aim of this study is to investigate the immunomodulatory effects of BM-MSCs in cyclophosphamide (CP)-induced lung damage of rats. Material and Methods: A total number of 40 female rats were divided into 4 groups (A, B, C &D). Group (A) served as a control group, this group was administered intraperitoneal sterile normal saline for 10 d, (10 animals). Thirty rats were treated with intraperitoneal cyclophosphamide at 70 mg/kg BW/d for 3 d, then equally subdivided into three subgroups (B, C, D): Group B (sacrificed after three days). Group C (Auto healing) was left without treatment for ten days. Group D (MSCs treated) was treated on the 4 th and 10 th days with male BM-derived MSCs in a dose of 3X106/KG BW, by intraperitoneal injection. After ten days animals were sacrificed, lung tissue was obtained and processed for light microscopy exam, and samples were taken to -80 for RNA extraction. The genes expression was estimated by real-time qPCR and the proteins were detected by immunohistochemistry. Results: BM-MSCs ameliorated the damaged lung. They reverted the mRNA levels of p53, caspase3, band cl2 more/less similar to those of the control group. Upregulation of the mRNA level of VEGF was noticed after BM-MSCs injection. Also, BM-MSCs exerted significant down-regulation of CD14, CD21, Akt and PI3K proteins expression after CP-induced upregulation of these proteins. Conclusion:This study confirmed that MSCs were ameliorating pulmonary inflammatory and fibrotic changes through their immunomodulatory effects, thus they are considered to be very promising pharmacological therapy for CP-induced lung toxicity.

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Bone marrow-derived mesenchymal stem cells modulate apoptosis and angiogenesis in cyclophosphamide-induced spleen injury in rats

Cited by 3 publications

References 0 publications

Azilsartan Modulates HMGB1/NF-κB/p38/ERK1/2/JNK and Apoptosis Pathways during Renal Ischemia Reperfusion Injury

Azilsartan Modulates HMGB1/NF-κB/p38/ERK1/2/JNK and Apoptosis Pathways during Renal Ischemia Reperfusion Injury

Curative Effect of AD-MSCs against Cisplatin-Induced Hepatotoxicity in Rats is Potentiated by Azilsartan: Targeting Oxidative Stress, MAPK, and Apoptosis Signaling Pathways

The potential ameliorative effect of Bone marrow Derived Mesenchymal Stem Cells on Cyclophosphamide Injured Lung in Adult Female Albino Rats

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