Pseudomonas aeruginosa-induced mitochondrial dysfunction inhibits proinflammatory cytokine secretion and enhances cytotoxicity in mouse macrophages in a reactive oxygen species (ROS)-dependent way. / 铜绿假单胞菌诱导的线粒体功能障碍以ROSä¾èµ–æ€§çš„æ–¹å¼æŠ‘åˆ¶ä¿ƒç‚Žç»†èƒžå› å­åˆ†æ³Œå¹¶å¢žå¼ºå°é¼ å·¨å™¬ç»†èƒžçš„ç»†èƒžæ¯’æ€§.

Pseudomonas aeruginosa belongs to the genus Pseudomonas and is a common Gram-negative, exclusively aerobic, conditionally pathogenic bacterium with the characteristics of easy colonization, mutation, and multidrug resistance (Deng et al., 2015; Azam and Khan, 2019; Jurado-Martín et al., 2021). It is mainly distributed in the air, soil, water, intestinal tract, and skin surface of humans and domestic animals and can cause complications such as ulcerative keratitis, otitis externa, skin and soft tissue infections, respiratory infections, sepsis, osteomyelitis, endocarditis, and urinary tract infections in burned or immunocompromised patients (Azam and Khan, 2019; Chai and Xu, 2020; Voth et al., 2020). P. aeruginosa is a naturally drug-resistant bacterium that is resistant to a wide range of antibiotics, making it one of the major opportunistic pathogens leading to in-hospital infections (Pang et al., 2019; Chai and Xu, 2020; Reynolds and Kollef, 2021). According to the surveillance report of the China Antimicrobial Resistance Surveillance System (CARSS, http://www.carss.cn), Gram-negative bacteria accounted for more than 70% of all bacterial infections, and P. aeruginosa accounted for 12.4%, 12.0%, and 12.2% in 2018, 2019, and 2020, respectively. Therefore, P. aeruginosa infection has become an important concern in public health care, and it is particularly important to gain insight into the means of host immune defense against P. aeruginosa infection.

Protective Activities of Scutellarin against Alcohol-Induced Acute Kidney Injury.

Acute alcohol consumption has adverse effects in the kidney, resulting in kidney damage and disease, which are typically accompanied by oxidation and inflammation. Scutellarin (SCU) is the major effective ingredient of breviscapine and its anti-inflammation and antioxidant efficacy has been previously reported. The present study revealed the protective effective of SCU as therapeutic medicine against alcohol-induced inflammation and oxidative stress, leading to acute kidney injury (AKI). The AKI model was established by giving 50 % ethanol (12 mL/kg) via lavage. Kidney tissues were collected and used for histopathology analysis, biochemical assays and qRT-PCR analysis. The therapeutic effects of SCU were evaluated by observing pathological changes from HE-stained kidney tissues. Additionally, the anti-inflammation activity of SCU was evaluated by measuring the relative mRNA expression levels of Tnf-α, Il-1ß, Il-6 and the activity of iNOS. The antioxidant capacity was assessed by measuring the lipid peroxidation marker 'MDA' and antioxidant enzymes activity of SOD, CAT and GSH-Px. The results showed that serious swelling and damage occurred in the renal tubular epithelium of alcohol intake group, accompanying with glomerular atrophy, necrosis and increase of inflammatory infiltration. SCU treatment significantly reduced the damage of diseased renal tubular epithelium and glomerular, and less inflammatory cell emerged. The inflammation cytokines expression levels were elevated and oxidative stress index decreased after alcohol intake compared to the control group. In conclusion, inflammation and oxidative stress occur in the kidney after acute and excessive alcohol intake, SCU exhibited protective roles via its anti-inflammation and antioxidant activity in AKI.

Protective Effects of Scutellarin on Acute Alcohol Intestinal Injury.

The present study aims to investigate the roles of scutellarin (SCU) on acute alcohol intestinal injury. Mice were divided into six groups: alcohol, three administration, negative control and positive drug bifendate control. The administration group mice were intraperitoneally injected with SCU for 3 consecutive days followed by alcohol gavage at an interval of 1 h. After the mice were sacrificed, colon tissue damage was evaluated by histopathological examination; the activities of inducible nitric oxide synthase (iNOS) and catalase (CAT), as well as the content of malondialdehyde (MDA) were detected using biochemical kits; the levels of inflammatory cytokines mRNA were determined by real-time fluorescence quantitative PCR; the protein expression levels of hemeoxygenase-1 (HO-1) and phosphorylated nuclear factor-ĸB p65 were measured via western blotting. The results showed that alcohol induced severe colon morphological degradation, epithelia atrophy, and more inflammatory cells infiltration in the submucosa. SCU treatment prevented this process, especially in the middle and high dose groups. Alcohol treatment caused excessive lipid peroxidation product accumulation of MDA, restrained the activity of antioxidant enzyme CAT, induced HO-1 expression in the colon, whereas low dose SCU treatment significantly down-regulated the MDA level, enhanced the CAT level, and accelerated HO-1 signals. SCU prevented alcohol stimulation triggered inflammatory response in colon tissues through significantly downregulating the iNOS activity, transcript levels of Tnf-α, Il-1ß and Il-6, and phosphorylation levels of NF-κB p65. These findings suggest that SCU protects the colon via antioxidant and anti-inflammatory mechanisms, making it a promising drug against alcohol-induced colon damage.

Ameliorative effect of scutellarin on acute alcohol brain injury in mice.

Drinking culture has high significance in both China and the world, whether in the entertainment sector or in social occasions; according to the World Health Organization's 2018 Global Alcohol and Health Report, about 3 million people died from excessive drinking in 2016, accounting for 5.3% of the total global deaths that year. Oxidative stress and inflammation are the most common pathological phenomena caused by alcohol abuse (Snyder et al., 2017). Scutellarin, a kind of flavonoid, is one of the main active ingredients extracted from breviscapine. It exerts anti-inflammatory, antioxidant, and vasodilation effects, and has been used to treat cardiovascular diseases and alcoholic liver injury. Although scutellarin can effectively alleviate multi-target organ injury induced by different forms of stimulation, its protective effect on alcoholic brain injury has not been well-defined. Therefore, the present study established an acute alcohol mice brain injury model to explore the effect of scutellarin on acute alcoholic brain injury. The study was carried out based on the targets of oxidative stress and inflammation, which is of great significance for the targeted therapy of clinical alcohol diseases.