The aim of the present work was to investigate possible protective effects of febuxostat, a highly potent xanthine oxidase inhibitor, against acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats. Male Sprague Dawley rats were randomly divided into six groups, as follows: (i) vehicle control group; (ii) and (iii) febuxostat 10 and febuxostat 15 groups, drug-treated controls; (iv) LPS group, receiving an intraperitoneal injection of LPS (7.5 mg/kg); (v) and (vi) febuxostat 10-LPS and febuxostat 15-LPS groups, receiving oral treatment of febuxostat (10 and 15 mg/kg/day, respectively) for 7 days before LPS. After 18 h administration of LPS, blood was collected for C-reactive protein (CRP) measurement. Bronchoalveolar lavage fluid (BALF) was examined for leukocyte infiltration, lactate dehydrogenase (LDH) activity, protein content, and total nitrate/nitrite. Lung weight gain was determined, and lung tissue homogenate was prepared and evaluated for oxidative stress. Tumor necrosis factor-α (TNF-α) was assessed in BALF and lung homogenate. Moreover, histological changes of lung tissues were evaluated. LPS elicited lung injury characterized by increased lung water content (by 1.2 fold), leukocyte infiltration (by 13 fold), inflammation and oxidative stress (indicated by increased malondialdehyde (MDA), by 3.4 fold), and reduced superoxide dismutase (SOD) activity (by 34 %). Febuxostat dose-dependently decreased LPS-induced lung edema and elevations in BALF protein content, infiltration of leukocytes, and LDH activity. Moreover, the elevated levels of TNF-α in BALF and lung tissue of LPS-treated rats were attenuated by febuxostat pretreatment. Febuxostat also displayed a potent antioxidant activity by decreasing lung tissue levels of MDA and enhancing SOD activity. Histological analysis of lung tissue further demonstrated that febuxostat dose-dependently reversed LPS-induced histopathological changes. These findings demonstrate a significant dose-dependent protection by febuxostat against LPS-induced lung inflammation in rats.

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BackgroundTissue microarray technology has provided a high throughput means of evaluating potential biomarkers in archival pathological specimens. This study was carried out in order to produce tissue microarray blocks using mechanical pencil tips without high cost.MethodConventional mechanical pencil tips (Rotring Tikky II Mechanical Pencil 1.0 mm) were used to cut out 1 mm wax cylinders from the recipient block, creating from 36 to 72 holes. Three cores of tumor areas were punched out manually by using the mechanical pencil tips from donor paraffin embedded tissue blocks and transferred to the holes of the paraffin tissue microarrays.ResultsThis technique was easy and caused little damage to the donor blocks. We successfully performed H&E slides and immunodetection without substantial tissue cylinder loss.ConclusionOur mechanical pencil tip technique is the most inexpensive easy technique among the literature. It also takes a reasonable amount of time and reduces antibody consumption during immunohistochemistry

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