Melatonin-Pretreated Mesenchymal Stem Cells Improved Cognition in a Diabetic Murine Model

Amin, Shaimaa Nasr; Sharawy, Nivin; Tablawy, Nashwa El; Elberry, Dalia Azmy; Youssef, Mary; Abdelhady, Ebtehal Gamal; Rashed, Laila Ahmed; Hassan, Sherif S.

doi:10.3389/fphys.2021.628107

Cited by 6 publications

(2 citation statements)

References 62 publications

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“…The average count of PKH26-labeled AD-MSCs were counted per section in 10 randomly nonoverlapping microscopic fields using power × 200 magnifications of the sections from each rat [ 41 ]. The results were carried out utilizing the Image-J/NIH software.…”

Section: Methodsmentioning

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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Section: Methodsmentioning

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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“…It should be kept in mind that the factors influencing the effect of melatonin on cells in vitro are the duration and mode of exposure, namely, continuous incubation or pre-treatment [ 24 , 26 , 42 ]. Studies have shown various effects of melatonin after 24 h of treatment, such as an enhancement of viability and anti-apoptotic and anti-oxidative activity [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Adipose-Derived Stem Cell Activity by Melatonin Receptors in Terms of Viability and Osteogenic Differentiation

Skubis-Sikora,

Sikora,

Małysiak

et al. 2023

Pharmaceuticals

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Melatonin is a hormone secreted mainly by the pineal gland and acts through the Mel1A and Mel1B receptors. Among other actions, melatonin significantly increases osteogenesis during bone regeneration. Human adipose-derived mesenchymal stem cells (ADSCs) are also known to have the potential to differentiate into osteoblast-like cells; however, inefficient culturing due to the loss of properties over time or low cell survival rates on scaffolds is a limitation. Improving the process of ADSC expansion in vitro is crucial for its further successful use in bone regeneration. This study aimed to assess the effect of melatonin on ADSC characteristics, including osteogenicity. We assessed ADSC viability at different melatonin concentrations as well as the effect on its receptor inhibitors (luzindole or 4-P-PDOT). Moreover, we analyzed the ADSC phenotype, apoptosis, cell cycle, and expression of MTNR1A and MTNR1B receptors, and its potential for osteogenic differentiation. We found that ADSCs treated with melatonin at a concentration of 100 µM had a higher viability compared to those treated at higher melatonin concentrations. Melatonin did not change the phenotype of ADSCs or induce apoptosis and it promoted the activity of some osteogenesis-related genes. We concluded that melatonin is safe, non-toxic to normal ADSCs in vitro, and can be used in regenerative medicine at low doses (100 μM) to improve cell viability without negatively affecting the osteogenic potential of these cells.

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Intranasal administration of berberine-loaded hydrogel ameliorates okadaic acid-induced cognitive deficit in mice

Mazahir,

Rahi,

Kaundal

et al. 2025

Chemical Engineering Journal

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Melatonin-Pretreated Mesenchymal Stem Cells Improved Cognition in a Diabetic Murine Model

Cited by 6 publications

References 62 publications

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

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

Regulation of Adipose-Derived Stem Cell Activity by Melatonin Receptors in Terms of Viability and Osteogenic Differentiation

Intranasal administration of berberine-loaded hydrogel ameliorates okadaic acid-induced cognitive deficit in mice

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