Transplantation of adipose-derived mesenchymal stem cells ameliorates acute hepatic injury caused by nonsteroidal anti-inflammatory drug diclofenac sodium in female rats

Abdelbaset‐Ismail, Ahmed; Tharwat, Abeer; Ahmed, Ahmed E.; Khamis, Tarek; El-Rahim, Ibrahim H. Abd; Alhag, Sadeq K.; Dowidar, Mohamed

doi:10.1016/j.biopha.2022.113805

Cited by 2 publications

(4 citation statements)

References 45 publications

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“…Interestingly, administration of AZIL, AD-MSCs, and their combinations to CISP-treated rats considerably improved all the assessed parameters as well as the liver histological modifications, suggesting less liver damage and better liver function, which may be happened as a result of their antioxidant action and their capacity to limit the release of oxidizing radicals via inhibiting the hepatic endoplasmic reticulum stress, which may be consistent with previous reports [ 15 , 55 , 64 ].…”

Section: Discussionsupporting

confidence: 91%

“…In addition, it is worth noting that MSCs promote liver regeneration by decreasing polymorphic nuclear cell infiltration and vacuolar degeneration in the damaged liver [ 15 ]. Besides, they have a strong immunomodulatory effect, which reduces inflammatory responses [ 83 ].…”

Section: Discussionmentioning

confidence: 99%

“…These findings corroborate those of Garg et al [ 91 ] in which AZIL increased Bcl-2 protein expression and decreased the expression of Bax and caspase-3 proteins in an in vivo model of myocardial ischemia–reperfusion injury and exerted an antiapoptotic effect. In addition, a recent study showed that AD-MSCs have the potential to reduce apoptosis in liver cells following acute liver injury induced by diclofenac sodium in rats by increasing the expression of the anti-apoptotic gene Bcl-2 and decreasing the expression of the proapoptotic gene Bax , as well as the cleaved caspase-3 protein, which is a potential executioner of apoptosis [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies using adipose tissue-derived MSCs (AD-MSCs) have shown enhanced liver histopathology and function [ 13 , 14 ]. In addition, the easy arrival to subcutaneous AD, its uncomplicated isolation procedures, and the reproducibility of sample collection render AD the most appealing source of MSCs [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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The Effects of Subtoxic Dose of Acetaminophen Combined With Exercise on the Liver of Rats

et al. 2023

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Regular physical exercise is beneficial to the body. Acute exercise causes oxidant stress in many tissues including the liver by creating an unbalanced status between oxidant and antioxidant levels. Analgesic drugs are commonly consumed to reduce the pain after exercise. Acetaminophen (APAP), commonly used as an over-the-counter analgesic, can cause hepatotoxicity. The aim of this study was to investigate the effect and underlying mechanisms of APAP at subtoxic dose, which is given after the acute and exhaustive exercise on the rat livers. Male Wistar rats weighing 200-250 g were divided into 6 groups each consisting of 7 rats/group; Control, APAP (250 mg/kg, ip), Acute Exercise (AEx), Acute Exhaustive Exercise (AEEx), Acute Exercise and APAP (AEx+APAP) and Acute Exhaustive Exercise and APAP (AEEx+APAP) groups. Rats were exercised at moderate intensity or exhaustive on the treadmill and then received APAP. Tissue MDA levels were significantly increased in AEEx, AEx+APAP and AEEx+APAP groups compared with the control. There was no significant difference in GSH levels between groups. Tissue Sirtuin1 (Sirt1) levels of APAP, AEx and AEEx groups were significantly less than control. There was no significant difference between groups in VEGF levels. Liver damage score was significantly higher in all groups compared with control group. As a result, this study shows that subtoxic dose of APAP treatment alone or in combination with acute or exhaustive treadmill exercise can cause oxidative liver damage by affecting Sirt1 levels and without affecting VEGF levels

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Transplantation of adipose-derived mesenchymal stem cells ameliorates acute hepatic injury caused by nonsteroidal anti-inflammatory drug diclofenac sodium in female rats

Cited by 2 publications

References 45 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

The Effects of Subtoxic Dose of Acetaminophen Combined With Exercise on the Liver of Rats

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