Effect of remote ischemic preconditioning on hepatic microcirculation and function in a rat model of hepatic ischemia reperfusion injury

Tapuria, Niteen; Junnarkar, Sameer P; Dutt, Neelanjana; Abu‐Amara, Mahmoud; Fuller, Barry; Seifalian, Alexander M.; Davidson, Brian R

doi:10.1111/j.1477-2574.2009.00006.x

Cited by 49 publications

(48 citation statements)

References 42 publications

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“…Several publications concerning the use of RIPC were published after the initial study of Kanoria 7 and the results were encouraging, as liver protection form IRI was uniformly identified [7][8][9][10]15 . Similar to these results, the present study demonstrates RIPC is effective in decreasing liver necrosis, as it shows a significant reduction of tissue necrosis in the RIPC group when compared to the I/R group (Figures 1 and 2).…”

Section: Discussionmentioning

confidence: 98%

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Effect of remote ischemic preconditioning in the expression of IL-6 and IL-10 in a rat model of liver ischemia-reperfusion injury

et al. 2015

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PURPOSE:To study the effect of remote ischemic preconditioning (RIPC) in ischemia-reperfusion (I/R) liver injury and in the expression of IL-6 and IL-10 in a rat model. METHODS:Thirty-six male rats were divided in three groups: Sham; I/R injury, a 45 minutes lobar liver ischemia and reperfusion; and RIPC, six cycles of four minutes of ischemia and four minutes of reperfusion on the right hindlimb followed by a 45 minutes lobar liver ischemia and reperfusion. Tissue and blood samples were collected after 1h and 3h of reperfusion for histopathological study, plasma cytokines and alanine aminotransferase (ALT) measurement. RESULTS:The histopathological study demonstrated a significant reduction in liver necrosis in the RIPC group (p<0,001). The ALT levels were also significant lower in the RIPC group (p<0.01). The cytokines assessment showed that IL-6 levels were increased in the RIPC group after 1h of reperfusion, in comparison to the I/R group (p<0.05). Interleukin-10 levels in RIPC groups did not differ significantly from I/R group. CONCLUSIONS:Remote ischemic preconditioning is effective in decreasing liver necrosis in a rat model of ischemia-reperfusion. The IL-6 expression is up-regulated and peaked at 60 min of reperfusion. There was no difference in IL-10 expression between the groups. Key words: Ischemic Preconditioning. Reperfusion Injury. Interleukin-6. Interleukin-10. Rats. Effect of remote ischemic preconditioning in the expression of IL-6 and IL-10 in a rat model of liver ischemia-reperfusion injuryActa

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Section: Discussionmentioning

confidence: 98%

“…More recently, several investigators studied the use of RIPC to reduce liver I/R injury [7][8][9][10] . All studies showed a protective effect in liver IRI, but the underlying mechanisms involved in RIPC have not yet been established 11 .…”

Section: Introductionmentioning

confidence: 99%

Effect of remote ischemic preconditioning in the expression of IL-6 and IL-10 in a rat model of liver ischemia-reperfusion injury

et al. 2015

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“…In recent decades, IR injury has become a topic of particular interest in the context of liver surgery and research. Studies have predominantly focused on RIPC, which is a strategy for harnessing the body's endogenous protective capabilities against the injury that is incurred during IR (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). NO is an essential mediator of the protection that is afforded by hind-limb RIPC against liver IR injury (25).…”

Section: Discussionmentioning

confidence: 99%

“…The protective mechanism of RIPC is highly complex (18)(19)(20)(21)(22) and involves the improvement of hepatic oxygenation (23), reduction of serum cytokine-induced neutrophil chemoattractant-1 levels (24), modulation of hepatic microcirculation (15) and activation of the soluble guanylate cyclase-cyclic guanosine monophosphate pathway (20), resulting in protective effects against IR injury. Notably, Abu-Amara et al (25) suggested that nitric oxide (NO) is an essential mediator of the protection that is afforded by hind-limb RIPC against liver IR injury.…”

Section: Introductionmentioning

confidence: 99%

“…Increasing evidence indicates that remote ischemic preconditioning (RIPC) represents a strategy for harnessing the body's endogenous protective capabilities to counter the injury that is incurred by IR in various organs (5)(6)(7)(8)(9)(10)(11)(12)(13), including the normal liver (14)(15)(16)(17). The protective mechanism of RIPC is highly complex (18)(19)(20)(21)(22) and involves the improvement of hepatic oxygenation (23), reduction of serum cytokine-induced neutrophil chemoattractant-1 levels (24), modulation of hepatic microcirculation (15) and activation of the soluble guanylate cyclase-cyclic guanosine monophosphate pathway (20), resulting in protective effects against IR injury.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-29a/b/c targets iNOS and is involved in protective remote ischemic preconditioning in an ischemia-reperfusion rat model of non-alcoholic fatty liver disease

et al. 2017

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Abstract. Remote ischemic preconditioning (RIPC) protects against the injury that is incurred by ischemia and reperfusion (IR); however, the role of RIPC in liver IR injury in non-alcoholic fatty liver disease (NAFLD) remains unclear. In this study, a NAFLD rat model was utilized in a series of different surgical procedures and molecular experiments. Rats of the IR group and the RIPC+IR group exhibited more severe injury than NAFLD control rats (in which the liver was prodded following a median-incision laparotomy). The liver condition, measured by serum alanine transaminase and aspartate transaminase levels, of the RIPC+IR group was better than that of the IR group. In addition, alanine transaminase and aspartate transaminase levels were lower in the RIPC+IR group compared with the IR group (P<0.001). Flow cytometry revealed that the cell apoptosis ratio was significantly lower in the RIPC+IR group than in the IR group (P<0.001). Reverse transcription-polymerase chain reaction (RT-qPCR) was used to assess miR-29a/b/c levels, revealing that they were significantly reduced in the RIPC and RIPC+IR groups, but did not vary in the IR group compared with the control group. RT-qPCR also revealed that iNOS mRNA levels were not significantly different among any of the NAFLD groups; however, western blot analysis indicated that iNOS protein levels were increased in the RIPC group and the RIPC+IR group compared with the control and IR groups. A luciferase reporter assay demonstrated that transfection with miR-29a/b/c mimics significantly decreased the luciferase activities of plasmids containing the wild-type iNOS 3'-untranslated region (UTR) (relative fluorescence intensity: 0.47±0.06 for miR-29a, 0.36±0.07 for miR-29b, 0.41±0.04 for miR-29c; P<0.001), whereas the activities of plasmids containing the mutant iNOS 3'-UTR sequence were not markedly affected [relative fluorescence intensity: 0.99±0.08 for miR-29a (P=0.1349), 0.99±0.09 for miR-29b (P= 0.1607), 0.97±0.07 for miR-29c (P= 0.1824)]. This suggested that miR-29a/b/c downregulates iNOS by directly targeting its 3'-UTR. In summary, the results suggest that RIPC has a protective effect in NAFLD liver IR injury, which may be due to reduced miR-29a/b/c levels in the skeletal muscle, leading to increased iNOS and, therefore, nitric oxide.

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Galactosylated hydroxyl‐polyamidoamine dendrimer targets hepatocytes and improves therapeutic outcomes in a severe model of acetaminophen poisoning‐induced liver failure

Porterfield

Sharma

Jimenez

et al. 2023

Bioengineering & Transla Med

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Toxicity to hepatocytes caused by various insults including drugs is a common cause of chronic liver failure requiring transplantation. Targeting therapeutics specifically to hepatocytes is often a challenge since they are relatively nonendocytosing unlike the highly phagocytic Kupffer cells in the liver. Approaches that enable targeted intracellular delivery of therapeutics to hepatocytes have significant promise in addressing liver disorders. We synthesized a galactose‐conjugated hydroxyl polyamidoamine dendrimer (D4‐Gal) that targets hepatocytes efficiently through the asialoglycoprotein receptors in healthy mice and in a mouse model of acetaminophen (APAP)‐induced liver failure. D4‐Gal localized specifically in hepatocytes and showed significantly better targeting when compared with the non‐Gal functionalized hydroxyl dendrimer. The therapeutic potential of D4‐Gal conjugated to N‐acetyl cysteine (NAC) was tested in a mouse model of APAP‐induced liver failure. A single intravenous dose of a conjugate of D4‐Gal and NAC (Gal‐D‐NAC) improved survival in APAP mice, decreased cellular oxidative injury and areas of necrosis in the liver, even when administered at the delayed time point of 8 h after APAP exposure. Overdose of APAP is the most common cause of acute hepatic injury and liver transplant need in the United States, and is treated with large doses of NAC administered rapidly within 8 h of overdose leading to systemic side effects and poor tolerance. NAC is not effective when treatment is delayed. Our results suggest that D4‐Gal is effective in targeting and delivering therapies to hepatocytes and Gal‐D‐NAC has the potential to salvage and treat liver injury with a broader therapeutic window.

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Effect of remote ischemic preconditioning on hepatic microcirculation and function in a rat model of hepatic ischemia reperfusion injury

Abstract: Using intravital microscopy, this study demonstrates that RIPC modulates hepatic microcirculation to reduce the effects of IRI. HO-1 may have a key role in the modulation of hepatic microcirculation and endothelial function.

Cited by 49 publications

References 42 publications

Effect of remote ischemic preconditioning in the expression of IL-6 and IL-10 in a rat model of liver ischemia-reperfusion injury

Effect of remote ischemic preconditioning in the expression of IL-6 and IL-10 in a rat model of liver ischemia-reperfusion injury

MicroRNA-29a/b/c targets iNOS and is involved in protective remote ischemic preconditioning in an ischemia-reperfusion rat model of non-alcoholic fatty liver disease

Galactosylated hydroxyl‐polyamidoamine dendrimer targets hepatocytes and improves therapeutic outcomes in a severe model of acetaminophen poisoning‐induced liver failure

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