The Carotenoid Compound of Saffron Crocetin Alleviates Effects of Ischemia Reperfusion Injury via a Mechanism Possibly Involving MiR-127.

Renal impairment is associated with high mortality rates in severely ill patients. The need to prevent and treat renal damage underlines the importance of understanding the pathophysiological mechanisms that characterize it. This could also enable early diagnosis and the design of alternative therapeutic approaches. The aim of this study is to investigate the effect of crocetin, a known antioxidant, on the prevention of renal damage due to ischemia-reperfusion injury and the investigation of the mechanisms involved. The present study was performed on C57BL/6 mice aged 10-12 weeks. The animals had access to water and food ad libitum. The experiment, as described in materials and methods, was completed at 24 h, in which case the kidneys were removed for further study, both at tissue morphology (with immunohistochemistry) and changes in the level of miRs' expression by qRT-PCR. Accordingly, using the automatic precision analyzer, the serum levels of the basic parameters currently used clinically for the monitoring of renal function were determined. The administration of crocetin, despite the short presence of the substance in the body, affects all the biochemical parameters analyzed (urea, creatinine, uric acid, and ions of Na, K, Cl, P, Mg and Ca), ​​causing significant decrease of their measured values. Crocetin also resulted in a significant limitation of the inflammation elements and the degree of epithelial damage. Furthermore, the administration of crocetin appears to restore levels of expression of miR21, miR127 and miR132.

Parecoxib's effects on anastomotic and abdominal wound healing: a randomized Controlled trial.

BACKGROUND: Current evidence regarding the effects of selective cyclooxygenase inhibitors on gastrointestinal anastomoses is controversial. An experimental randomized control study was conducted in our institution to histopathologically evaluate the consequences of parecoxib, on intestinal and abdominal wound healing. METHODS: Twenty-four adult Wistar rats underwent laparotomy, ascending colon transection, and hand-sewn anastomosis. They were randomized to receive either parecoxib (0.5 mg/kg twice daily) or 0.9% normal saline by intraperitoneal injection postoperatively. Animals were euthanatized either on the third or the seventh postoperative day. Semiquantitative methods were used to evaluate both intestinal and abdominal wounds for inflammatory cell composition, angiogenesis, fibroblasts, granular tissue, collagen deposition, epithelization, and presence of necrosis, exudate, and abscess formation. Results are presented as (parecoxib: median [IQR] versus control: median [IQR], P-value). RESULTS: No macroscopic anastomotic leakage or wound dehiscence was observed. Intestinal anastomoses in the parecoxib group, showed significantly decreased epithelization (2 [1] versus 3 [1], [P = 0.004]) and collagen deposition (2 [0] versus 3 [1], [P = 0.041]). No difference was observed in angiogenesis (3 [1] versus 2.5 [1], [P = 0.158]). Abdominal wall specimens appeared to demonstrate decreased epithelization (2 [2] versus 4 [0.5], [P = 0.0004]) in the treatment group. No difference between the two groups was identified regarding collagen deposition (2.5 [1] versus 2 [0.5], [P = 0.280]) and angiogenesis (2.5 [1] versus 2 [1], [P = 0.633]). Necrosis was significantly more present in the parecoxib group in both specimen types, (3.5 [1] versus 2.5 [1], [P = 0.017]) and (3 [1] versus 1 [0.5], [P < 0.0001]). CONCLUSIONS: The present study shows that despite the absence of clinical adverse effects, parecoxib can impair anastomotic and abdominal wound healing on a histopathological level.

Effects of Lornoxicam on Anastomotic Healing: A Randomized, Blinded, Placebo-Control Experimental Study.

Introduction and Aim. With the implementation of multimodal analgesia regimens, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are often administered for optimal pain control and reduction of opioid use. The aim of the study was to examine the effects of lornoxicam, a NSAID, on anastomotic healing employing an animal model. Materials and Methods. A total of 28 Wistar rats were randomly assigned in two groups. All animals underwent ascending colonic transection followed by an end-to-end hand sewn anastomosis. Group 1 received intraperitoneally lornoxicam before and daily after surgery. Group 2 received intraperitoneally an equal volume of placebo. Half of the animals in each group were euthanized on the 3rd pod and the remaining on the 7th pod. Macro- and microscopic indicators of anastomotic healing were compared using a two-tailed Fisher exact test. Results. The lornoxicam group significantly decreased fibroblast in growth and reepithelization of the mucosa at the anastomotic site on the 3rd pod and significantly increased occurrence of deep reaching defects, necrosis, and microabscess on the 7th pod. Conclusion. Lornoxicam administration during the perioperative period adversely affects histologic parameters of intestinal anastomotic healing. These effects of lornoxicam administration were not found to induce significant increase of anastomotic dehiscence in the rat model.

Protein expression in the brain of rat offspring in relation to prenatal caloric restriction.

OBJECTIVE: Intrauterine growth restriction (IUGR) has been associated with decreased supply of crucial substrates to the fetus and affects its growth and development by temporarily or permanently modifying gene expression and function. However, not all neonates born by calorie restricted mothers are IUGR and there are no reports regarding their brain protein expression vis-à-vis that of their IUGR siblings. Here, we investigated the expression of key proteins that regulate growth and development of the brain in non-IUGR newborn pups versus IUGR siblings and control pups. METHODS: Rat brain proteins were isolated from each group upon delivery and separated by two-dimensional gel electrophoresis (2-DE). RESULTS: 14-3-3 Protein, calreticulin, elongation factor, alpha-enolase, fascin, heat-shock protein HSP90 and pyruvate kinase isozymes were significantly increased (p < 0.05) in samples obtained from IUGR newborn pups compared to non-IUGR. Conversely, collapsin response mediator proteins, heat-shock70 and peroxiredoxin2 were decreased in IUGR group compared to non-IUGR. CONCLUSIONS: In our experimental study, IUGR pups showed an altered proteomic profile compared to their non-IUGR siblings and non-IUGR controls. Thus, not all offspring of calorie-restricted mothers become IUGR with the accompanying alterations in the expression of proteins. The differentially expressed proteins could modulate alterations in the energy balance, plasticity and maturation of the brain.

Aberrant expression of collapsin response mediator proteins-1, -2 and -5 in the brain of intrauterine growth restricted rats.

Intrauterine growth restriction (IUGR) has been associated with increased perinatal morbidity, higher incidence of neurodevelopmental defects and increased risk for adult metabolic syndrome manifestations. Altered protein expression profiles associated with IUGR may be informative on the pathological mechanisms of this condition and might reveal potential markers for postnatal complications. We hypothesized that nutrient manipulation of the pregnant rat might influence the expression of important neurodevelopmental proteins in the resultant IUGR offspring. Therefore, we aimed to determine in newborn rat brain tissue the expression of collapsin response mediator proteins (CRMPs)-1, -2 and -5, commonly referred to as dihydropyrimidinase-related proteins (DPYLs) - playing a role in axon guidance, invasive growth and cell migration - and compare it to the corresponding expression in control rats. Two-dimensional electrophoresis and mass spectrometry, as well as Western blot analysis were employed in brain tissue from 24 IUGR newborn rats and 24 controls. With both methods, CRMP-1, CRMP-2 and CRMP-5 were decreased in the brains of the IUGR group as compared to the control group at the time of delivery. In conclusion, IUGR rat offspring are born with a decreased expression of CRMPs, suggesting that these proteins may be implicated in fetal stress-induced programming.