Effect of erythropoietin on liver regeneration in an experimental model of partial hepatectomy.

BACKGROUND AND AIM: The liver shows remarkable regeneration ability after damage or resection. The main stimulant for hepatic regeneration is resection. Erythropoietin (EPO), which was initially used for anemia therapy, is today known as a general tissue protector owing to its anti-inflammatory, anti-oxidant, anti-apoptotic, and angiogenic properties. This study aims to investigate the effect of systemically administered EPO on liver regeneration after partial hepatectomy. METHODS: Forty-eight male Wistar albino rats were randomly split in two groups A and B consisting of 24 rats each. Standard 70% hepatectomy was performed on the rats in group A. The same surgical procedure was performed on the rats in group B, and they were additionally administered 3000 U/kg/subcutaneous EPO. The rats were sacrificed 24, 48, and 72 h after resection. The groups were compared in terms of biochemical, morphological, and histopathological parameters. RESULTS: The biochemical results showed that the administration of EPO decreased aspartate aminotransferase levels significantly (p < 0.05) at 24 h after hepatectomy. A comparison of the groups in terms of relative liver weight showed that EPO-treated groups exhibited a statistically significant increase (p < 0.05) for all three time periods. Histopathology results showed that in the EPO-treated groups, the mitosis index at 48 and 72 h, double nuclei cell number at 72 h, and proliferating cell nuclear antigen ratio at 48 h showed a significant increase (p < 0.05). CONCLUSION: Our study showed that systemically administering high-dose EPO increases regeneration by affecting the biochemical, morphological, and histopathological parameters after liver resection.

Does sildenafil reverse the adverse effects of ischemia on ischemic colon anastomosis: yes, 'no'.

INTRODUCTION: Sildenafil may lead an improvement in anastomotic healing of ischemic left colon anastomosis. METHODS: Thirty-six male Wistar albino rats were randomized into four experimental groups (n=9 in each group). In group 1, a well-perfused left colonic segment was transected, and free ends were anatomosed. In groups 2, 3 and 4 animals underwent a standardized surgical procedure to induce ischemic left colon anastomosis. Group 2 animals received only tap water. In groups 3 and 4 animals received 10mg/kg/body-weight and 20mg/kg/body-weight sildenafil, single dose a day during 4 days, respectively. Rats were sacrificed on day 4 following operation. Anastomotic integrity, intra-peritoneal adhesion scores, anastomotic bursting pressures and tissue hydroxyproline levels were recorded. Histopathological examination of the anastomosis was also performed. RESULTS: There was no statistically significant difference among groups with respect to anastomotic integrity (p=0.142) but ischemia decreased the anastomotic bursting pressure. The mean bursting pressure values were 78.8+/-24.1, 43.3+/-26, 55.1+/-32.4, and 43.3+/-20.4 in groups 1, 2, 3, and 4, respectively. Group 1 had the highest values whereas; there was no statistically significant difference between groups 1 and 3. There was no statistically significant difference among groups 2, 3, and 4 with respect to tissue hydroxyproline levels, adhesion scores and the Chiu scores. The highest inflammatory cell presence in the granulation tissue was detected in group 2, whereas the lowest was detected in group 4 (p=0.0001). The highest fibroblast infiltration in the granulation tissue was detected in group 1 (p=0.045). DISCUSSION: Our results showed that 10mg/kg sildenafil decreased the adverse effects of ischemia on the healing of ischemic left colon anastomosis. Additional investigations are needed to confirm the effects of phosphodiesterase-5 inhibitors in ischemic colon anastomosis models.

Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis.

AIM: To investigate the effect of exogenous erythro-poietin (EPO) administration on acute lung injury (ALI) in an experimental model of sodium taurodeoxycholate- induced acute necrotizing pancreatitis (ANP). METHODS: Forty-seven male Wistar albino rats were randomly divided into 7 groups: sham group (n = 5), 3 ANP groups (n = 7 each) and 3 EPO groups (n = 7 each). ANP was induced by retrograde infusion of 5% sodium taurodeoxycholate into the common bile duct. Rats in EPO groups received 1000 U/kg intramuscular EPO immediately after induction of ANP. Rats in ANP groups were given 1 mL normal saline instead. All animals were sacrificed at postoperative 24 h, 48 h and 72 h. Serum amilase, IL-2, IL-6 and lung tissue malondialdehyde (MDA) were measured. Pleural effusion volume and lung/body weight (LW/BW) ratios were calculated. Tissue levels of TNF-alpha, IL-2 and IL-6 were screened immunohistochemically. Additionally, ox-LDL accumulation was assessed with immune-fluorescent staining. Histopathological alterations in the lungs were also scored. RESULTS: The mean pleural effusion volume, calculated LW/BW ratio, serum IL-6 and lung tissue MDA levels were significantly lower in EPO groups than in ANP groups. No statistically significant difference was observed in either serum or tissue values of IL-2 among the groups. The level of tumor necrosis factor-alpha (TNF-alpha) and IL-6 and accumulation of ox-LDL were evident in the lung tissues of ANP groups when compared to EPO groups, particularly at 72 h. Histopathological evaluation confirmed the improvement in lung injury parameters after exogenous EPO administration, particularly at 48 h and 72 h. CONCLUSION: EPO administration leads to a significant decrease in ALI parameters by inhibiting polymorphonuclear leukocyte (PMNL) accumulation, decreasing the levels of proinflammatory cytokines in circulation, preserving microvascular endothelial cell integrity and reducing oxidative stress-associated lipid peroxidation and therefore, can be regarded as a cytoprotective agent in ANP-induced ALI.