Thymoquinone and curcumin modify inducible nitric oxide synthase, caspase 3, and thioredoxin immunohistochemical expression in acetaminophen hepatotoxicity.

BACKGROUND: Acetaminophen (APAP) hepatotoxicity is characterised by an extensive oxidative stress due to depletion of glutathione (GSH), which results in massive lipid peroxidation and subsequent liver injury. The current paradigm suggests that mitochondria are the main source of reactive oxygen species (ROS), which impair mitochondrial function and are responsible for cell signalling resulting in cell death. This study was designed to compare the potential impact of thymoquinone (THQ), and/or curcumin (CURC) on liver injury induced by APAP toxicity in rats. MATERIALS AND METHODS: Serum levels of alanine transaminase, aspartate transaminase, total bilirubin, and total protein were measured. In addition, liver nitric oxide (NO), malondialdehyde, reduced glutathione (GSH), and superoxide dismutase (SOD) were estimated. Moreover, these biochemical parameters were confirmed by histopathological and immunohistochemical investigations for the expression of thioredoxin, iNOS and caspase 3. RESULTS: Acetaminophen toxicity elevated most of the above-mentioned parameters but decreased GSH, SOD, and total protein levels. Histologically, liver sections demonstrated liver injury characterised by hepatocellular necrosis with nuclear pyknosis, karyorrhexis and karyolysis. Immunohistochemical study revealed increased expression of iNOS and caspase 3 proteins, while the thioredoxin protein expression was decreased. CONCLUSIONS: Treatment with the THQ and CURC regulated the biochemical and histopathological alterations induced by APAP toxicity. It was concluded that the combination strategy of THQ and CURC might be considered as a potential antidote in combating liver injury induced by APAP with minimal side effects.

The Value of Spirometry in Subglottic Stenosis.

The diagnosis of subglottic stenosis (SGS) is usually made by clinical assessment and definitively by a direct endoscopic examination. This study aimed to evaluate different spirometric values in relation to anatomical grading and severity of subglottic stenosis cases of upper airway obstruction. Cases of SGS that underwent dilatational procedures endoscopically at the otolaryngology department of the King Saud University Medical City, Riyadh, Saudi Arabia, from June 2015 to October 2017 were collected. Pulmonary function test (PFT) pre- and postoperative parameters and the grades of subglottic stenosis were extracted. We compared different spirometric values to the severity of SGS and compared the pre- and postoperative results for each patient. There were 19 cases with a valid PFT study within 7 days preoperatively in addition to a documented intraoperative grading according to the Myer-Cotton grading system; 7 (36.8%) were grade 1, 8 (42.1%) were grade 2, and 4 (21.1%) were grade 3. The actual preoperative ratio of forced expiratory volume (FEV1) in 1 second to peak expiratory flow (PEF) for all 19 patients ranged from 7.34 to 21.40 mL/L/min. We found a significant improvement in all spirometric parameters postdilatation including PEF ( P < .001), FEV1 ( P < .001), FEV1/PEF ( P = .001), forced expiratory flow (FEF) from 25%, 50%, and 75% of vital capacity, respectively, FEF25 ( P < .001), FEF50 ( P = .001), FEF75 ( P = .048), and maximum mid-expiratory flow ( P = .002). We did not find any correlation between the severity of stenosis and spirometric values. This study revealed that spirometry is a useful marker in following up patients with subglottic stenosis and is also a good indicator to determine postairway surgery outcomes. However, these markers do not correlate with anatomical grading and the severity of subglottic stenosis.