The influence of allopurinol and post-conditioning on lung injuries induced by lower-limb ischemia and reperfusion in Wistar rats

Abstract

1 AbstractPurpose: To analyze the effects of allopurinol and of post-conditioning on lung injuries induced by lower-limb ischemia and reperfusion. Methods: Thirty rats were used. They were divided in 5 groups: (1) group A: abdominal aortic dissection only, (2) group B: ischemia and reperfusion, (3) group C: administered allopurinol (100mg/Kg) a few hours before procedure, (4) group D: post-conditioned and (5) group E: administered allopurinol and post-conditioned. With the exception of group A, all groups were submitted to infrarenal aortic ischemia for 2 hours, and reperfusion for 72 hours. After euthanasia, lungs were removed for histological analysis. They were graded under two scores: pulmonary injury (neutrophil infiltration, interstitial edema, vascular congestion, and destruction of lung architecture) and lymphocytic score (neutrophil infiltration, lymphoid aggregate and secondary follicle). Results: On the pulmonary injury score, the degree of injury was smaller than in groups D and E, when compared to group B, p<0.05. Group C did not obtain the same result (p>0,05). On the lymphocytic score, there was no statistic difference among groups, p>0.05. Conclusion: Both post-conditioning and the combination of allopurinol and post-conditioning were effective in remote lung protection induced by lower-limbs I/R. When used in isolation, allopurinol showed no protective effect.

The Prospective Effect of Allopurinol on the Oxidative Stress Index and Endothelial Dysfunction in Covid-19

“…observed that hyperuricemia is linked with ED through inhibition of endothelial NO [ 50 ]. A previous study confirmed that allopurinol improves ED by regulating endothelial NO synthesis and release [ 49 , 51 ]. Therefore, allopurinol reduces uric acid or independently reduces the risk of ED, OS, and coagulopathy, as revealed in the present study.…”

“…Taken together, activated HMGB-1 and RAGE are linked with the development of ED and Covid-19 severity [ 48 ]. Furthermore, hyperuricemia may trigger a prothrombotic status due to the development of ED, OS, and endothelial inflammation [ 49 ]. Otani et al .…”

The effects of ischaemic conditioning on lung ischaemia–reperfusion injury

“…Besides in situ LIRI, conditioning exerts protection in cases of remote organ reperfusion. In the setting of aortic occlusion and reperfusion, RIC was associated with reduced alveolar oedema, congestion, and neutrophil infiltration [18,57]. Similar benefits have been derived from hepatosplanchnic conditioning, which abrogated the P-selectin upregulation caused by IRI, with an attendant reduction in alveolar and perivascular neutrophil infiltration, reduced MDA levels, and preserved vascular permeability [58].…”

“…Leukocyte emigrationLi et al[10]; Song et al[17]; Dorsa et al[18]; Luo et al[19]; Waldow et al[20]; Li et al[48]; Zhou et al[56]; Akahane et al[57]; Peralta et al[58]; Neto et al[59]; Harkin et al[62]; Olguner et al[63]; Jan et al[66]; Leung et al[67]; Bergmann et al[68]; Jin et al[69] ↓ Oxidative stress Li et al [7]; García-de-la-Asunción et al [8]; Li et al [10]; Zhou et al [12]; Li et al [13]; Lin et al [14]; Song et al [17]; Li et al [48]; Du et al [49]; Soncul et al [51]; Kandilci et al [52]; Li et al [53]; Peralta et al [58]; Meng et al [60]; Olguner et al [63]; Jan et al [66]; Jin et al [69]; Chen et al [71]; ↓ Inflammatory/ ↑Anti-inflammatory cytokines Zhou et al [12]; Li et al [7]; Li et al [13]; Lin et al [14]; Song et al [17]; Luo et al [19]; Waldow et al [20]; Zhou et al [56]; Meng et al [60]; Leung et al [67]; Bergmann et al [68] Inflammatory genes downregulation Jun et al [55] ↓ Pulmonary vasoconstrictors Li et al [10]; Li et al [48]; Jin et al [69] ↓ Non-cardiogenic pulmonary oedema Li et al [10]; Song et al [17]; Dorsa et al [18]; Luo et al [19]; Gasparri et al [50]; Kandilci et al [52]; Li et al [53]; Friedrich et al [54]; Zhou et al [56]; Akahane et al [57]; Peralta et al [58]; Meng et al [60]; Harkin et al [62]; Olguner et al [63]; Jan et al [66] Improved gas exchange Li et al [7]; García-de-la-Asunción et al [8]; Li et al [10]; Zhou et al [12]; Li et al [13]; Lin et al [14]; Song et al [17]; Luo et al [19]; Waldow et al [20]; Li et al [48]; Du et al [49]; Li et al [53]; Friedrich et al [54]; Harkin et al [62]; Jan et al [66]; Bergmann et al [68]; Jin et al [69]; Chen et al [71]; Lin et al [72]; Xia et al [77]; Min et al [78] Improved lung mechanics Li et al [7]; Zhou et al [12]; Li et al [13]; Friedrich et al [54]; Cheung et al [70]; Featherstone et al [75]; Kharbanda et al [76] Improved pulmonary haemodynamics Li et al [10]; Waldow et al [20]; Li et al [48]; Soncul et al [51]; Kandilci et al [52]; Li et al [53]; Harkin et al [62]; Xia et al [77]…”

Lung damage reduction due to reperfusion injury of acute lower limb ischemia with and without pentoxifylline and vitamin c combination therapy: histopathological evaluation

“…Although this anti-leukocyte strategy has received limited clinical attention, it is effective in experimental animals with IRI. 9,13, 14 Administration of allopurinol, which aims to protect tissue from IRI, has been studied both in experimental animals and in humans. Administration of allopurinol reduces serum TNF-α concentrations in IRI thereby reducing inflammation caused by IRI.…”