Adipose-Derived Stem Cell Transplantation Attenuates Inflammation and Promotes Liver Regeneration after Ischemia-Reperfusion and Hemihepatectomy in Swine

Aim. To study the anti-inflammatory and liver regenerative effects of adipose-derived mesenchymal stem cells (ADSCs) on a porcine model of ischemia-reperfusion (IR) and hemihepatectomy. Methods. Eighteen healthy Bama miniature pigs were randomly divided into the sham-operated (sham), untreated IR injury (IRI), and ADSC-transplanted (ADSC) groups. Hepatic IR was established by laparoscopic hemihepatectomy. ADSCs were transplanted directly into the liver parenchyma after the surgery. Hepatic inflammation and liver regeneration were evaluated by histopathological examination and assessment of relevant cytokines and other factors. Results. ADSC transplantation successfully ameliorated the IRI-induced histopathological damage and the high levels of pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α. In addition, the ADSCs enhanced the expression of the anti-inflammatory IL-10, regenerative factors including HGF, Cyclin D1, and proliferating cell nuclear antigen (PCNA), and angiogenic factors like VEGF, ANG-1, and ANG-2. Conclusions. ADSCs attenuated the hepatic IRI-induced inflammatory response and promoted liver regeneration.

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Antioxidant and Anti-Inflammatory Effects of Diallyl Disulfide on Hepatotoxicity Induced by Cyclophosphamide in Rats

Natural Product Communications ◽

10.1177/1934578x20969083 ◽

2020 ◽

Vol 15 (10) ◽

pp. 1934578X2096908

Author(s):

Hesham Farouk Hasan ◽

Gehan Roushdy Abdel-Hamid ◽

Sahar Ismail Ebrahim

Keyword(s):

Inflammatory Responses ◽

Histopathological Examination ◽

Hepatic Function ◽

Nuclear Antigen ◽

Diallyl Disulfide ◽

Significant Amelioration ◽

Intraperitoneal Dose ◽

Anti Inflammatory ◽

Proliferating Cell ◽

And Oxidative Stress

Diallyl disulfide (DADS) is a garlic-derived organo-sulfur compound. This study was carried out to investigate the protective potential, antioxidant, and anti-inflammatory effects of this compound against cyclophosphamide (CP)-induced hepatotoxicity in rats. A single intraperitoneal dose of CP (200 mg/kg) resulted in a significant disturbance in hepatic function and oxidative stress, as well as inflammatory biomarkers. In addition, histopathological examination showed distinct changes and increased expression of proliferating cell nuclear antigen in hepatocytes. On the other hand, daily oral preadministration of DADS (200 mg/kg) for 10 days before the CP dose effectively attenuated the hepatotoxicity caused by CP administration as confirmed by significant amelioration of the aforementioned parameters in rat’s liver. It could be concluded that administration of DADS can diminish CP-induced hepatotoxicity through concurrent upregulation of antioxidant and anti-inflammatory responses that denote its possible potential clinical application against side effects of the CP drug.

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Focal intra-colon cooling reduces organ injury and systemic inflammation after REBOA management of lethal hemorrhage in rats

Scientific Reports ◽

10.1038/s41598-021-93064-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Awadhesh K. Arya ◽

Kurt Hu ◽

Lalita Subedi ◽

Tieluo Li ◽

Bingren Hu

Keyword(s):

Inflammatory Response ◽

Inflammatory Cytokines ◽

Troponin I ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Balloon Catheter ◽

Organ Injury ◽

Upper Body ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

AbstractResuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving maneuver for the management of lethal torso hemorrhage. However, its prolonged use leads to distal organ ischemia–reperfusion injury (IRI) and systemic inflammatory response syndrome (SIRS). The objective of this study is to investigate the blood-based biomarkers of IRI and SIRS and the efficacy of direct intestinal cooling in the prevention of IRI and SIRS. A rat lethal hemorrhage model was produced by bleeding 50% of the total blood volume. A balloon catheter was inserted into the aorta for the implementation of REBOA. A novel TransRectal Intra-Colon (TRIC) device was placed in the descending colon and activated from 10 min after the bleeding to maintain the intra-colon temperature at 37 °C (TRIC37°C group) or 12 °C (TRIC12°C group) for 270 min. The upper body temperature was maintained at as close to 37 °C as possible in both groups. Blood samples were collected before hemorrhage and after REBOA. The organ injury biomarkers and inflammatory cytokines were evaluated by ELISA method. Blood based organ injury biomarkers (endotoxin, creatinine, AST, FABP1/L-FABP, cardiac troponin I, and FABP2/I-FABP) were all drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated these increased organ injury biomarkers. Plasma levels of pro-inflammatory cytokines TNF-α, IL-1b, and IL-17F were also drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated the pro-inflammatory cytokines. In contrast, TRIC12°C significantly upregulated the levels of anti-inflammatory cytokines IL-4 and IL-10 after REBOA. Amazingly, the mortality rate was 100% in TRIC37°C group whereas 0% in TRIC12°C group after REBOA. Directly cooling the intestine offered exceptional protection of the abdominal organs from IRI and SIRS, switched from a harmful pro-inflammatory to a reparative anti-inflammatory response, and mitigated mortality in the rat model of REBOA management of lethal hemorrhage.

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P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0527a ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Dan Li ◽

Chenyu Li ◽

Yan Xu

Keyword(s):

Inflammatory Cytokines ◽

Inflammatory Cytokine ◽

Ischemia Reperfusion ◽

Kidney Injury ◽

Tnf Α ◽

Public Dataset ◽

Anti Inflammatory ◽

Anti Inflammatory Cytokine ◽

Pro Inflammatory Cytokines

Abstract Background and Aims Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear. Method Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P<0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR. Results The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression. Conclusion These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI Figure KLF6, AKI, Control Inflammation

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Effect of the aqueous extract of Sida cordifolia on liver regeneration after partial hepatectomy

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502006000700009 ◽

2006 ◽

Vol 21 (suppl 1) ◽

pp. 37-39 ◽

Cited By ~ 13

Author(s):

Renata Lemos Silva ◽

Gustavo Barreto de Melo ◽

Valdinaldo Aragão de Melo ◽

Ângelo Roberto Antoniolli ◽

Paulo Roberto Teixeira Michellone ◽

...

Keyword(s):

Oral Administration ◽

Liver Regeneration ◽

Partial Hepatectomy ◽

Aqueous Extract ◽

Proliferating Cell Nuclear Antigen ◽

Nuclear Antigen ◽

Hepatic Regeneration ◽

Control Group ◽

Sida Cordifolia ◽

Proliferating Cell

PURPOSE: The use of medicinal plants for the treatment of human diseases has increased worldwide. Many of them are used by oral administration and, after absorption, may affect many organs. Therefore, this study aimed at assessing the effects of the aqueous extract of Sida cordifolia leaves, popularly known in Brazil as "malva-branca", on liver regeneration. METHODS: Twenty rats were divided into four groups: control, Sida100, Sida200 and Sida400 groups. All animals were submitted to oral administration of distilled water, 100, 200 and 400 mg/kg of the aqueous extract of Sida cordifolia, respectively. Immediately after this, they underwent 67% partial hepatectomy. Twenty four hours later, their livers were removed. Hepatic regeneration was assessed by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) using the PC-10 monoclonal antibody. RESULTS: Sida100 and Sida200 groups disclosed higher liver regeneration indices than control group (p<0.001 and p<0.05, respectively). CONCLUSION: The aqueous extract of Sida cordifolia stimulates liver regeneration after 67% partial hepatectomy in rats.

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Role of AT1 angiotensin II receptors in renal ischemic injury

AJP Renal Physiology ◽

10.1152/ajprenal.1998.274.1.f79 ◽

1998 ◽

Vol 274 (1) ◽

pp. F79-F90 ◽

Cited By ~ 17

Author(s):

Jimmy Kontogiannis ◽

Kevin D. Burns

Keyword(s):

Serum Creatinine ◽

Ischemia Reperfusion ◽

Renin Angiotensin System ◽

Ischemic Injury ◽

Nuclear Antigen ◽

Ang Ii ◽

Receptor Mrna ◽

Proximal Tubular ◽

Proliferating Cell

The present studies determined the effect of renal ischemia/reperfusion on components of the intrarenal renin-angiotensin system in rats and evaluated the effect of AT1angiotensin (ANG) II receptor blockade on functional recovery. After bilateral renal pedicle occlusion for 60 min, serum creatinine increased, peaking at 72 h, and returned to sham levels after 120 h. ANG II levels in ischemic kidneys were significantly increased 24 h after reperfusion but did not differ from levels in sham kidneys after 120 h. Both renal cortical angiotensinogen mRNA and proximal tubular AT1 receptor mRNA were significantly reduced early after reperfusion, returning to sham levels by 120 and 72 h, respectively. AT2ANG II receptor mRNA was undetectable in proximal tubules from sham rats but was consistently present in ischemic rats at 120 h. By histoautoradiography, we found that binding of125I-labeled ANG II was preserved in glomeruli but was decreased in whole cortex and outer medulla early after reperfusion and was completely blocked by the AT1 antagonist losartan. Treatment of rats with losartan (25 mg/kg sc daily), starting at the time of reperfusion, had no effect on expression of proliferating cell nuclear antigen in cortical tubules but caused a significant decrease in serum creatinine at 72 h (ischemia: 334 ± 69 μM vs. ischemia + losartan: 135 ± 28 μM; P < 0.025, n = 6). These data indicate that renal ischemic injury causes an early increase in intrarenal ANG II levels, associated with reduction of mRNA for angiotensinogen and proximal tubular AT1 receptors, and maintenance of glomerular ANG II binding. Losartan accelerates recovery of renal function, suggesting that activation of AT1 receptors impairs glomerular filtration in the postischemic kidney.

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Resina Draconis Reduces Acute Liver Injury and Promotes Liver Regeneration after 2/3 Partial Hepatectomy in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/2305784 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Zhi-yong He ◽

Kai-han Lou ◽

Jia-hui Zhao ◽

Ming Zhang ◽

Lan-chun Zhang ◽

...

Keyword(s):

Liver Injury ◽

Liver Regeneration ◽

Partial Hepatectomy ◽

Acute Liver Injury ◽

Liver Weight ◽

Nuclear Antigen ◽

Protective Effects ◽

Weight Restoration ◽

Resina Draconis ◽

Proliferating Cell

Aim. To investigate the protective effects and possible mechanisms of action of resina draconis (RD) on acute liver injury and liver regeneration after 2/3 partial hepatectomy (PH) in mice. Methods. 2/3 PH was used to induce acute liver injury. Mice were divided into three groups: sham, vehicle + 2/3 PH, and RD + 2/3 PH. Resina draconis was administered intragastrically after 2/3 PH into the RD + 2/3 PH group, and the same volume of vehicle (1% sodium carboxymethyl cellulose) was injected into the vehicle + 2/3 PH group and sham group mice. The index of liver to body weight (ILBW) and proliferating cell nuclear antigen (PCNA) were assayed to evaluate liver regeneration. Blood and liver tissues were collected for serological and western blotting analysis. Results. Resina draconis protected against 2/3 PH-induced acute severe liver injury and promoted liver regeneration as shown by significantly increased ILBW compared with that of controls. 2/3 PH increased serum AST and ALT levels, which were significantly decreased by RD treatment, while 2/3 PH decreased serum TP and ALB, which were increased by RD treatment. In the RD + 2/3 PH group, PCNA expression was significantly increased compared with the 2/3 PH group. Further, hepatocyte growth factor (HGF), TNFα, and EGFR levels were increased in the RD group at postoperative days 2 and 4 compared with the those in the 2/3 PH group. Conclusion. Our results suggest that RD ameliorates acute hepatic injury and promotes liver cell proliferation, liver weight restoration, and liver function after 2/3 PH, probably via HGF, TNFα, and EGFR signaling.

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Proliferative effect of the aqueous extract of Hyptis pectinata on liver regeneration after partial hepatectomy in rats

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502006000700008 ◽

2006 ◽

Vol 21 (suppl 1) ◽

pp. 33-36 ◽

Cited By ~ 2

Author(s):

Gustavo Barreto Melo ◽

Renata Lemos Silva ◽

Valdinaldo Aragão Melo ◽

Ângelo Roberto Antoniolli ◽

Paulo Roberto Teixeira Michellone ◽

...

Keyword(s):

Liver Regeneration ◽

Partial Hepatectomy ◽

Aqueous Extract ◽

Proliferating Cell Nuclear Antigen ◽

Serum Enzymes ◽

Nuclear Antigen ◽

Proliferative Effect ◽

Water Administration ◽

Proliferating Cell ◽

Hepatic Protection

PURPOSE: This study was carried out to assess the effects of the aqueous extract of Hyptis pectinata leaves on liver regeneration and on serum enzymes (AST, ALT and gamma-GT) after 67% partial hepatectomy in rats. METHODS: AST, ALT and gamma-GT, were determined by conventional procedures using a spectrophotometer (Model E2250-CELM). Liver regeneration was evaluated by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). RESULTS:Oral pretreatment during 4 days at 100 mg/kg increased liver regeneration index. At 200 mg/kg, AST level was statistically decreased in comparison to the group submited to distilled water administration. The other enzymes assessed disclosed no difference when all groups were compared. CONCLUSION: The present study shows that the aqueous extract of Hyptis pectinata leaves contains some biological active principles that stimulate liver regeneration at 100 mg/kg and cause slight hepatic protection at 200 mg/kg.

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The effect of laser on remanescent liver tissue after 90% hepatectomy in rats

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502006000700007 ◽

2006 ◽

Vol 21 (suppl 1) ◽

pp. 29-32 ◽

Cited By ~ 9

Author(s):

Alexandre Ferreira Oliveira ◽

Tiago Castro e Silva ◽

Ajith Kumar Sankarankutty ◽

Eduardo Garcia Pacheco ◽

Juliana Ferreira ◽

...

Keyword(s):

Partial Hepatectomy ◽

Proliferating Cell Nuclear Antigen ◽

Proliferative Activity ◽

Wistar Rats ◽

Liver Parenchyma ◽

Serum Levels ◽

Nuclear Antigen ◽

Serum Aminotransferases ◽

Hepatic Injuries ◽

Proliferating Cell

PURPOSE: To evaluate the effect of laser beam on remanescent liver after partial hepatectomy 90%. METHODS: Wistar rats, (N= 42), were divided into six groups with seven specimens each. The partial hepatectomy (HP) was performed in all animals through exeresis of approximately 90% of the liver parenchyma. The animals from groups HP and Laser application, HPL24, HPL48 and HPL72 undertook laser irradiation carried out through application (dose of 22.5 J/cm²) in five different sites in the remanescent liver. The rats were then sacrificed 24, 48 and 72hours after HP procedure, for the liver regeneration analysis,using the Proliferating Cell Nuclear Antigen (PCNA),and for dosage of serum aminotransferases. RESULTS: Were demonstrated an increase of the serum levels of alanine aminotransferase for the group of 24 hours and a decrease for the group of 72 hours exposed to laser. The index of marked cells had a considerable more improvement for the group of 72 hours exposed in laser compared to other groups. CONCLUSION: Laser did not cause hepatic injuries additional to the partial hepatectomy and perhaps led to a benefit by stimulating the proliferative activity.

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