Investigation of the protective effect of enoxaparin and ticagrelor pretreatment against ischemia-reperfusion injury in rat lung tissue

Abstract

SUMMARY OBJECTIVES This study was conducted to reveal the possible protective effects of ticagrelor and enoxaparin pretreatment against ischemia-reperfusion (IR)-induced injury on the lung tissue of a rat model. METHODS Wistar albino rats were randomly divided into 4 groups as follows: group-1 (control-sham), group-2 (control-saline+IR), group-3 (ticagrelor+IR), group-4 (enoxaparin+IR). Before the ischemic period, saline, ticagrelor, and enoxaparin were administered to the 2nd-4th groups, respectively. In these groups, IR injury was induced by clamping the aorta infrarenally for 2 h, followed by 4 h of reperfusion except group-1. After the rats were euthanized, the lungs were processed for histological examinations. Paraffin sections were stained with Haematoxylin&Eosin (H&E) for light microscopic observation. Apoptosis was evaluated by caspase-3 immunoreactivity. Data were statistically analyzed using the SPSS software. RESULTS In the lung sections stained with H&E, a normal histological structure was observed in group-1, whereas disorganized epithelial cells, hemorrhage, and inflammatory cell infiltration were seen in the alveolar wall in group-2. The histologic structure of the treatment groups was better than that of group-2. Caspase-3(+) apoptotic cells were noticeable in sections of group-2 and were lower in the treatment groups. In group-4, caspase-3 immunostaining was lower than in group-3. In group-2, apoptotic cells were significantly higher than in the other groups (p<0.001). CONCLUSION Based on the histological results, we suggested that both therapies ameliorated the detrimental effects of IR. Caspase-3 immunohistochemistry results also revealed that pre-treatment with enoxaparin gave better results in an IR-induced rat injury model. In further studies, other parameters such as ROS and inflammatory gene expressions should be evaluated for accurate results.

Effects of melatonin on protecting against lung injury (Review)

“…Lung ischaemia-reperfusion injury (LIRI), known as a frequent and severe clinical complication, has a high mortality after lung transplantation worldwide (80,81). LIRI is a pathological process with the clinical feature of initial restriction of blood supply to lung organs followed by the restoration of perfusion, which involves oxidative stress (82).…”

Changes in cardiac cells due to ticagrelor and enoxaparin in a rat ischemia/reperfusion model

“…The approximate percentage of apoptotic cells was estimated based on 10 representative fields in each section. The immunostaining intensity was scored as negative (−), very weak (1+), moderate (2), strong (3+), and very strong (4+) [7][8][9][10] .…”

“…Group 1 was not treated. Before the ischemic period, Group 2 received 0.1 mL/kg saline, Group 3 received 25 mg/kg ticagrelor (Brilinta, AstraZeneca, Södertalje, Sweden) via gastric gavage while Group 4 received 0.75 mg/kg enoxaparin (Clexane, Sanofi Winthrop Industrie, Maisons-Alfort, France) subcutaneously 6,7 .…”

Ticagrelor alleviates pyroptosis of myocardial ischemia reperfusion-induced acute lung injury in rats: a preliminary study

“…Recent studies have shown that ticagrelor might reduce infection occurrences in the clinic, especially for pneumonia ( Li et al, 2021 ; Storey et al, 2014 ; Varenhorst et al, 2012 ). Furthermore, ticagrelor alleviates ALI and/or inflammation in vivo against infections, including abdominal sepsis and pneumonia, and in response to myocardial ischemia-reperfusion injury ( Fındık et al, 2019 ; Lancellotti et al, 2019 ; Rahman et al, 2014 ). Ticagrelor inhibits several pyroptosis-associated proteins, including NLRP3, adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD) (ASC), and caspase-1 in cells as well as several experimental models ( Birnbaum et al, 2016 ; Chen et al, 2020 ; Huang et al, 2020 ; Penna et al, 2020 ).…”