Protective effects of crocin and zinc sulfate on hepatic ischemia-reperfusion injury in rats: a comparative experimental model study

Mard, Seyyed Ali; Akbari, Ghaidafeh; Dianat, Mahin; Mansouri, Esrafil

doi:10.1016/j.biopha.2017.09.123

Cited by 33 publications

(25 citation statements)

References 53 publications

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“…Our study demonstrated that the hepatic ischemia for 30 min followed by 30 min of reperfusion led to liver injury as evidenced by significant elevation of liver enzymes, ALT, and AST, levels which indicating hepatocytes damage. These results are in accordance with previous studies (Mard et al, ; Uylas et al, ). Moreover, these effects were supported by the histological changes observed in IR rats in the form of perivascular edema, few areas of focal hemorrhage, vacuolar degeneration, and swelling of hepatocytes, with nuclear condensation, pyknosis, fragmentation, and signs of cellular necrosis.…”

Section: Discussionsupporting

confidence: 94%

Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF‐κB‐p65/TLR‐4, JAK1/STAT‐3, Nrf‐2, and PI3K/Akt/mTOR Signaling Pathways

Kamel

Hassanein

Ahmed

et al. 2019

The Anatomical Record

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Hepatic ischemia reperfusion (IR) is an inevitable clinical problem for surgical procedures such as liver transplantation and liver resection. This study was designed to evaluate the protective effect of perindopril (PER) against hepatic IR injury. Thirty‐two rats were used and randomly allocated into four groups. Sham control group was subjected to sham operation and received saline only, IR group was subjected to IR and received vehicle, PER group was pretreated with PER (one milligram per kilogram per day i.p. for 10 consecutive days), and IR+PER group was pretreated with PER then subjected to IR. Liver function biomarkers (aspartate aminotransferase and alanine aminotransferase), oxidative stress (glutathione, malondialdehyde, myeloperoxidase, and superoxide dismutase) and inflammation markers (tumor necrosis factor‐alpha, interferon‐gamma, and inteleukin‐10 [IL‐10]), mRNA expression of NF‐κB‐p65 and TLR‐4, as well as protein expression of JAK1, STAT‐3, PI3K, mTOR, Akt, and Nrf‐2 were investigated concomitantly with histopathological examination. The results indicated that, hepatic IR induced a significant alteration in liver function biomarkers and structure, oxidative stress, and inflammation. At the molecular level, up‐regulation of NF‐κB‐p65, TLR‐4, JAK1, and STAT‐3 concomitantly with down‐regulation of Nrf‐2, IL‐10, PI3K, Akt, and mTOR were observed. These disturbances were alleviated by pretreatment of IR rats with PER in concomitant with hepatic structural improvement. Conclusively, the protective effect of PER presumably may be relevant to its ability to reduce oxidative stress, ameliorate the inflammatory processes, and modify the related signaling pathways. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1935–1949, 2020. © 2019 American Association for Anatomy

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Section: Discussionsupporting

confidence: 94%

Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF‐κB‐p65/TLR‐4, JAK1/STAT‐3, Nrf‐2, and PI3K/Akt/mTOR Signaling Pathways

Kamel

Hassanein

Ahmed

et al. 2019

The Anatomical Record

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“…Our study exhibited that the HI for 45 minutes followed by 3 hours of reperfusion led to the liver injury which is assessed by marked elevation of liver enzymes ALT and AST levels indicating damage in the cell membrane of the liver and this is in accordance with previous studies [ 25 , 35 , 36 ]. Moreover, hepatic necrosis, sinusoidal congestion, hemorrhage, and hepatocyte degeneration are the characteristic pathological changes seen after HIR [ 24 , 34 , 37 ].…”

Section: Discussionsupporting

confidence: 93%

“…The HIR injury was performed as described in previous studies [ 22 , 23 ]. Rats were anesthetized with a mixture of ip 80 mg/kg ketamine (Ketamax-50, Troikaa Pharmaceuticals Ltd., Gujarat, India) and 10 mg/kg xylazine (Xyla-Ject®, Adwia Co., 10th of Ramadan, Egypt) [ 24 , 25 ]. A midline abdominal incision was made after shaving the rats' abdominal front wall and disinfected by the povidone-iodine solution.…”

Section: Methodsmentioning

confidence: 99%

Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury via the TLR4/NF‐κB Signaling Pathway

Sherif

Al-Shaalan

2018

Oxidative Medicine and Cellular Longevity

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The Toll-like receptor-4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway is vital in the pathogenesis of hepatic ischemia/reperfusion (HIR) injury. Dipeptidyl peptidase-4 (DPP4) inhibitors exert protective effects on IR injury of the kidney, heart, and lung; however, their effect on the liver is still unknown. Thus, the purpose of this study was to examine whether pretreatment with vildagliptin (Vilda), a DPP4 inhibitor, produces hepatic protection against IR injury and to investigate its influence on TLR4/NF-κB signaling in a rat model. Thirty male Wistar rats were divided into 3 groups: the sham group: subjected to a sham operation and received normal saline; the HIR group: subjected to HIR and received normal saline; and the Vilda + HIR group: subjected to HIR with pretreatment of 10 mg/kg/day Vilda for 10 days intraperitoneally. Hepatic ischemia lasted for 45 minutes followed by 3-hour reperfusion; then blood and liver samples were collected for biochemical and histopathological examination. The HIR group produced a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA), nitric oxide (NO), and tumor necrosis factor alpha (TNF-α) levels and a significant reduction in the hepatic catalase level in comparison to the sham group. Moreover, a significant upregulation of gene and protein expressions of TLR4, NF-κB, and high-mobility group box-1 (HMGB1) along with caspase-3 protein expression was observed in the HIR group when compared with the sham group. Histopathological examination of the liver from the HIR group showed necrosis, sinusoidal congestion, hemorrhage, and hepatocyte degeneration. Administration of Vilda ameliorated the biochemical and histopathological changes caused by HIR. Vildagliptin showed for the first time a hepatoprotective effect in HIR injury through downregulation of TLR4/NF-κB/HMGB1 and caspase-3 hepatic expressions.

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“…The author further showed that inhibition of miR-122 contributed to crocin’s protective effects on liver IRI. Mard et al [ 80 ] also found that crocin, ZnSO 4 , and their combination, protected the liver against IRI by inhibiting miR-122 expression. Collectively, miR-122 serves as not only a novel biomarker, but also a potential therapeutic target for liver IRI.…”

Section: Mirnas and Liver Irimentioning

confidence: 99%

“…Akbari et al found that [ 79 ] crocin pretreatment also ameliorated liver IRI by inhibiting miR-34a expression. Moreover, Mard et al [ 80 ] found that inhibition of miR-34a contributed to the protective effects of ZnSO 4 and crocin cocktail in liver IRI. Collectively, miR-34a exerts deleterious effects in liver IRI by inhibiting the expression of Nrf2 and SIRT1.…”

Section: Mirnas and Liver Irimentioning

confidence: 99%

Novel Targets for Treating Ischemia-Reperfusion Injury in the Liver

Yang

Chen

Meng

et al. 2018

IJMS

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Liver ischemia-reperfusion injury (IRI) is a major complication of hemorrhagic shock, liver transplantation, and other liver surgeries. It is one of the leading causes for post-surgery hepatic dysfunction, always leading to morbidity and mortality. Several strategies, such as low-temperature reperfusion and ischemic preconditioning, are useful for ameliorating liver IRI in animal models. However, these methods are difficult to perform in clinical surgeries. It has been reported that the activation of peroxisome proliferator activated receptor gamma (PPARγ) protects the liver against IRI, but with unidentified direct target gene(s) and unclear mechanism(s). Recently, FAM3A, a direct target gene of PPARγ, had been shown to mediate PPARγ’s protective effects in liver IRI. Moreover, noncoding RNAs, including LncRNAs and miRNAs, had also been reported to play important roles in the process of hepatic IRI. This review briefly discussed the roles and mechanisms of several classes of important molecules, including PPARγ, FAM3A, miRNAs, and LncRNAs, in liver IRI. In particular, oral administration of PPARγ agonists before liver surgery or liver transplantation to activate hepatic FAM3A pathways holds great promise for attenuating human liver IRI.

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Protective effects of crocin and zinc sulfate on hepatic ischemia-reperfusion injury in rats: a comparative experimental model study

Cited by 33 publications

References 53 publications

Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF‐κB‐p65/TLR‐4, JAK1/STAT‐3, Nrf‐2, and PI3K/Akt/mTOR Signaling Pathways

Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF‐κB‐p65/TLR‐4, JAK1/STAT‐3, Nrf‐2, and PI3K/Akt/mTOR Signaling Pathways

Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury via the TLR4/NF‐κB Signaling Pathway

Novel Targets for Treating Ischemia-Reperfusion Injury in the Liver

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