The effect of Farnesoid X receptor agonist tropifexor on liver damage in rats with experimental obstructive jaundice

ABSTRACT Purpose: To investigate experimentally the effects of Tropifexor, a farnesoid X receptor agonist, on liver injury in rats with obstructive jaundice. Methods: Forty healthy Wistar albino female rats were divided randomly in selected groups. These groups were the sham group, control group, vehicle solution group, Ursodeoxycholic acid group and Tropifexor group. Experimental obstructive jaundice was created in all groups, except the sham one. In the blood samples obtained, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin and direct bilirubin levels were established and recorded. Additionally, liver malondialdehyde, myeloperoxidase and catalase enzyme activity in the tissue samples were studied. Histopathological analysis was also performed. Results: No statistical difference was found between the control group and the Tropifexor group when AST, ALT and ALP values were compared. However, it was found that the Tropifexor group had statistically significant decreases in the values of GGT, total bilirubin and direct bilirubin (p < 0.05). Additionally, Tropifexor decreased the median values of malondialdehyde and myeloperoxidase, but this difference was not statistically significant compared to the control group. Finally, the Tropifexor group was statistically significant in recurring histopathological liver damage indicators (p < 0.05). Conclusions: Tropifexor reduced liver damage due to obstructive jaundice.

The influence of platelet-rich plasma (PRP) on colonic anastomosis healing impaired by intraperitoneal 5-flourouracil application. An experimental study

Abstract Purpose 5-flourourasil (5-FU) is commonly used for early intraperitoneal chemotherapy in colorectal or appendiceal cancer patients with peritoneal carcinomatosis. Due to its effect, anastomosis healing can be impaired and leads to anastomotic leakage. In this study, we aimed to investigate the potential healing effect of platelet-rich plasma (PRP) on colonic anastomosis impaired by intraperitoneal 5-flourouracil application. Methods After ten rats were sacrificed for preparing PRP, forty Wistar-albino rats were subjected to colonic anastomosis, and randomly allocated into four groups including 10 rats each. According to receiving PRP and/or 5-FU application, the groups were formed as control (C), 5-FU without PRP (CT), anastomosis with PRP (C-PRP), and 5-FU with PRP (CT-PRP). CT and CT-PRP groups also received 5-FU intraperitoneally on postoperative day 1 (POD 1). All animals were euthanized on pod 7. The body weight change, anastomotic bursting pressure (ABP), tissue hydroxiprolin (TH) and histopathological examination of each group were analyzed. Results 5-FU application significantly reduced ABP levels when compared with group C, C-PRP and CT-PRP (for each comparison, p<0,01). PRP application in CT-PRP group raised the measure of ABP up to the levels of C group. Although tissue hydroxyproline levels (THL) levels of CT-PRP group were found higher than CT group, it was not significant (p=0.112). Microscopically, comparing with CT group, PRP application significantly promoted the healing of colonic anastomosis subjected to 5-FU application by improving tissue edema, necrosis, submucosal bridging and collagen formation (p<0.05). Tissue healing in CT-PRP group was observed as good as the control groups. (C, C-PRP, p=0.181, p=0.134; respectively). Conclusion PRP administration on colonic anastomosis significantly promotes the healing process of anastomosis in rats receiving 5-FU. This result encourages further clinical use of PRP to reduce the frequency of AL in patients receiving EPIC.

The potential efficacy of Survanta (r) and Seprafilm (r) on preventing intra-abdominal adhesions in rats

ABSTRACT PURPOSE: To investigate the potential efficacy of beractant (Survanta(r)) and Seprafilm(r) on the prevention of postoperative adhesions. METHODS: Forty Wistar-albino female rats were used. The rats were randomly allocated into four groups of 10 rats each as control group (CG), beractant group (BG), Seprafilm(r) group (SG), and combined group (COG). All rats underwent cecal abrasion via midline laparotomy. Before abdominal closure, isotonic saline, beractant, Seprafilm, and combined agents were intraperitoneally administered. Adhesions were classified macroscopically with Canbaz Scoring System on postoperative day 10. Ceacum was resected for histopathological assessment. RESULTS: Macroscopic adhesion scores were significantly lower in BG, SG, and COG than CG (p<0.05); (45%, 15%, 25%, and 15%; respectively). Histopathological assessment revealed a reduced inflammation and fibrosis score in the study groups than CG (p<0.05). In BG, adhesion development, inflammation and fibrosis scores were lower than SG; however, it was not statistically significant. CONCLUSIONS: Intra-abdominal application of beractant is significantly effective for the prevention of adhesion formation with no adverse effect by covering the whole peritoneal mesothelium with excellent gliding properties in a rat model. The combination of both agents is also effective in reducing adhesion formation, however, not superior to single beractant application.

The effects of vardenafil and pentoxifylline administration in an animal model of ischemic colitis

OBJECTIVES: Vardenafil enhances dilatation of vascular smooth muscle and inhibits platelet aggregation. The purpose of this study was to evaluate the clinical effects of vardenafil and pentoxifylline administration in an experimental model of ischemic colitis. METHODS: Forty female Wistar albino rats weighing 250-300 g were randomized into five experimental groups (each with n = 8) as follows:1) a sham group subjected to a sham surgical procedure and administered only tap water; 2) a control group subjected to a standardized surgical procedure to induce ischemic colitis and administered only tap water; 3) and 4) treatment groups subjected to surgical induction of ischemic colitis followed by the postoperative administration of 5 mg/kg or 10 mg/kg vardenafil, respectively; and 5) a treatment group subjected to surgical induction of ischemic colitis followed by postoperative administration of pentoxifylline at 50 mg/kg/day per day as a single dose for a 3-day period. All animals were sacrificed at 72 h post-surgery and subjected to relaparotomy. We scored the macroscopically visible damage, measured the ischemic area and scored histopathology to determine the severity of ischemia. Tissue malondialdehyde levels were also quantified. RESULTS: The mean Gomella ischemic areas were 63.3 mm2 in the control group; 3.4 and 9.6 mm2 in the vardenafil 5 and vardenafil 10 groups, respectively; and 3.4 mm2 in the pentoxifylline group (p = 0.0001). The mean malondialdehyde values were 63.7 nmol/g in the control group; 25.3 and 25.6 nmol/g in the vardenafil 5 and vardenafil 10 groups, respectively; and 22.8 nmol/g in the pentoxifylline group (p = 0.0001). CONCLUSION: Our findings indicate that vardenafil and pentoxifylline are effective treatment options in an animal model of ischemic colitis. The positive clinical effects produced by these drugs are likely due to their influence on the hemodynamics associated ...

Reduction of postsurgical adhesions in a rat model: a comparative study

BACKGROUND: Adhesion formation after peritoneal surgery is a major cause of postoperative bowel obstruction, infertility, and chronic pelvic pain. In this study, we compared the possible individual effects of phosphatidylcholine (PC), Seprafilm® II, and tissue plasminogen activator (t-PA) and the combined effects of phosphatidylcholine and t-PA on postoperative adhesion formation in a rat surgical model. MATERIALS AND METHODS: A total of 50 Wistar male rats underwent median laparotomy and standardized abrasion of the visceral and parietal peritoneum. phosphatidylcholine, Seprafilm II, and t-PA alone and phosphatidylcholine and t-PA in combination were applied intraperitoneally at the end of the surgical procedure. Seven days after surgery, a relaparotomy was performed for adhesion grading and histopathological examination. RESULTS: A comparison of adhesion stages demonstrated a significant difference between the control group and the study groups (p<0.001). The adhesion grade of the combined treatment group was statistically different from that of the other groups (p<0.05). In the t-PA group and the combined group, six and two rats, respectively, developed hematomas locally on the cecum. CONCLUSIONS: PC, t-PA, and Seprafilm II used individually reduced the adhesion grade. The t-PA and phosphatidylcholine combination was most effective in reducing adhesion formation. On the other hand, usage of t-PA alone or in combination may increase risk of bleeding. More detailed studies are needed, and future studies on the efficacy of a material for decreasing adhesion formation should include a comparison of several control materials in the same model.