Silibinin treatment results in reducing OPA1&amp;MFN1 genes expression in a rat model hepatic ischemia–reperfusion

Qajari, Neda Masoumi; Shafaroudi, Majid Malekzadeh; Gholami, Milad; Khonakdar-Tarsi, Abbas

doi:10.1007/s11033-020-05383-w

Cited by 12 publications

(7 citation statements)

References 20 publications

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“…In line with the previous studies, our results showed that Cx26, Cx32, and Cx43 mRNA levels were up-regulated during the hepatic IR. It was also revealed that silibinin administration during IR could reduce endothelial damages, inflammation, and glycogen depletion; in addition, it preserved the mitochondrial membrane, which protected the liver against the IRI (21,26,27). It was also determined in this study that silibinin could reduce the expression of Cx26 and Cx32; however, it could induce the expression of the Cx43 gene.…”

Section: Discussionsupporting

confidence: 49%

Alteration of connexins gene expression by silibinin during hepatic warm ischemia-reperfusion injury in the rat model

Ghobadi

Mousavi

Mosavi

et al. 2021

ircmj

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Background: Ischemia-reperfusion injury (IRI) is an injurious phenomenon that is the primary determinant of liver dysfunction after surgery and transplantation. The present evidence demonstrated that connexin 43 (Cx43), Cx32, and Cx26 are the essential gap junction proteins involved in the liver IRI. This study aimed to characterize the beneficial effects of silibinin on Cx43, Cx32, and Cx26 gene expression during warm hepatic ischemia-reperfusion (IR). Materials and Methods: A total of 32 male Wistar rats weighing 250-300 g were randomly divided into four equal groups of eight animals in each group as follows: 1) control group (laparotomy+normal saline), 2) laparotomy+silibinin (30 mg/kg) (SILI), 3) liver IR procedure+normal saline (IR), and 4) liver IR procedure+silibinin (30 mg/kg) (IR+SILI). After 1 h of ischemia followed by 3 h of reperfusion, blood samples and tissue sections were gathered to assess the serum liver markers and evaluate the liver histological changes as well as gene expression, respectively. Results: The obtained data proved no considerable differences between control and SILI groups in all experiments. Furthermore, the gene expression of Cx26, Cx32, and Cx43 was significantly induced in the IR group, compared to the control group. Silibinin markedly reduced Cx26 and Cx32 mRNA expression, whereas increased Cx43 mRNA expression. Moreover, serum alanine aminotransferase and aspartate aminotransferase levels were markedly elevated in the IR group (P<0.001), compared to the control group. However, in the IR+SILI group, silibinin could significantly decline these elevations, compared to the IR group. In addition, silibinin diminished hepatic tissue damages during IR. Conclusion: Silibinin could attenuate liver injury through better cell-to-cell communication via lowering Cx32 and Cx26, as well as increasing Cx43 gene expression, respectively.

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Section: Discussionsupporting

confidence: 49%

Alteration of connexins gene expression by silibinin during hepatic warm ischemia-reperfusion injury in the rat model

Ghobadi

Mousavi

Mosavi

et al. 2021

ircmj

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“…First of all, as a result of studying the antioxidant e cacy of silibinin, DPPH radical scavenging assay did not show the antioxidant activity of silibinin, but it showed that silibinin tended to increase in proportion to the concentration in the reducing power assay. Previous studies that silibinin with high hepatoprotective, antioxidant, angiogenesis inhibition and anticancer properties contains polyphenol and is thus reported to be effective in cell cycle and apoptosis inhibition, leading to cell death [15][16][17][18][19]. ROS induces the damage of DNA through guanine, nucleobases oxidation, altered bases cause mutations and have long been associated with tumors [20].…”

Section: Discussionmentioning

confidence: 99%

Silibinin inhibits human cancer fibrosarcoma cell invasion through MMPs, p-p38, and IL-1β expression

Kim

2022

Preprint

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Background Silibinin is a single compound of silymarin that is obtained from the seeds of milk thistle plants. Their natural compound has an alternative function to suppress lung cancer and liver protection. Normal cells are converted into cancer cells due to defects in the genes that regulate cell division. Cancer cells break down vascular walls and basal membranes to obtain sufficient oxygen and nutrients, causing metastasis to other tissues. Therefore, the development of natural substances to suppress metastasis through MMPs, the metastatic enzymes, is necessary. Our investigation aimed to study the activation of silibinin on metastasis inhibition of human cancer fibrosarcoma cells.Methods and Results The cytotoxicity of silibinin in HT1080 cells was measured by MTT assay. The gelatinolytic activities of MMP-2 and MMP-9 expression were determined by using a gelatin zymography assay. Western blot analysis and immunofluorescence assay was performed to investigate the protein expression of silibinin on metastasis inhibition. Silibinin above 5 μM showed reducing power activity. Even though the cell cytotoxicity was measured in the presence of silibinin below 5 μM, the cell cytotoxicity of silibinin was shown above 15 μM. Silibinin above 20 μM remarkably inhibited the levels of MMP-2 and MMP-9 activation under PMA treatment conditions. Furthermore, silibinin at 25 μM suppressed metastasis by reducing the levels of TIMP-1, MMP-2, IL-1β, ERK1/2, and p-p38 expression and silibinin above 10 μM inhibited cell invasion on HT1080 cells.Conclusion These results suggest that silibinin could exert an excellent effect on the suppression of metastatic enzymes, leading to the inhibition of cell invasion.

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“…Knocking-out toll-like receptor 4 (TLR4), a protein involved in inflammation, resulted in the upregulation of MFN2 and PGC-1α, and thus improving mitochondrial function and reducing LIRI [ 65 ]. However, amelioration of LIRI was also verified by treating mice with silibinin which decreased the levels of mitochondrial fusion-related proteins MFN1 and OPA1 [ 66 ].…”

Section: Mitochondrial Function and Dynamics During Liver I/rmentioning

confidence: 99%

Preservation of Mitochondrial Health in Liver Ischemia/Reperfusion Injury

2023

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Liver ischemia-reperfusion injury (LIRI) is a major cause of the development of complications in different clinical settings such as liver resection and liver transplantation. Damage arising from LIRI is a major risk factor for early graft rejection and is associated with higher morbidity and mortality after surgery. Although the mechanisms leading to the injury of parenchymal and non-parenchymal liver cells are not yet fully understood, mitochondrial dysfunction is recognized as a hallmark of LIRI that exacerbates cellular injury. Mitochondria play a major role in glucose metabolism, energy production, reactive oxygen species (ROS) signaling, calcium homeostasis and cell death. The diverse roles of mitochondria make it essential to preserve mitochondrial health in order to maintain cellular activity and liver integrity during liver ischemia/reperfusion (I/R). A growing body of studies suggest that protecting mitochondria by regulating mitochondrial biogenesis, fission/fusion and mitophagy during liver I/R ameliorates LIRI. Targeting mitochondria in conditions that exacerbate mitochondrial dysfunction, such as steatosis and aging, has been successful in decreasing their susceptibility to LIRI. Studying mitochondrial dysfunction will help understand the underlying mechanisms of cellular damage during LIRI which is important for the development of new therapeutic strategies aimed at improving patient outcomes. In this review, we highlight the progress made in recent years regarding the role of mitochondria in liver I/R and discuss the impact of liver conditions on LIRI.

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Silibinin treatment results in reducing OPA1&MFN1 genes expression in a rat model hepatic ischemia–reperfusion

Cited by 12 publications

References 20 publications

Alteration of connexins gene expression by silibinin during hepatic warm ischemia-reperfusion injury in the rat model

Alteration of connexins gene expression by silibinin during hepatic warm ischemia-reperfusion injury in the rat model

Silibinin inhibits human cancer fibrosarcoma cell invasion through MMPs, p-p38, and IL-1β expression

Preservation of Mitochondrial Health in Liver Ischemia/Reperfusion Injury

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