Mechanism of adrenocortical toxicity induced by quinocetone and its bidesoxy-quinocetone metabolite in porcine adrenocortical cells in vitro

Quinocetone (QCT) is a new feeding antibacterial agent in the QdNOs family. The mechanism of its adrenal toxicity is far from clear. This study was conducted to estimate the adrenal cell damage induced by QCT and its bidesoxy-quinocetone (B-QCT) metabolite and to further investigate their mechanisms. Following doses of QCT increasing from 5 to 50 μM, cell apoptosis and necrosis, mitochondrial dysfunction and redox imbalance were observed in porcine adrenocortical cells. The mRNA levels of the six components of intermediary enzymes and the adrenal renin-angiotensin-aldosterone system (RAAS) displayed a dysregulation induced by QCT, indicating that QCT might influence aldosterone secretion not only through the upstream of the production but also through the downstream of the adrenal RAAS pathway. In contrast, B-QCT had few toxic effects on the cell apoptosis, mitochondrial dysfunction and redox imbalance. Moreover, LCMS-IT-TOF analysis showed that no desoxy metabolites of QCT were found in either cell lysate or supernatant samples. In conclusion, we reported on the cytotoxicity in porcine adrenocortical cells exposed to QCT via oxidative stress, which raised awareness that its toxic effects resulted from N→O groups, and its toxic mechanism might involve the interference of the steroid hormone biosynthesis pathway.     

The Oxidant-Antioxidant Balance in Mild Asthmatic Patients

We investigated the oxidant-antioxidant balance and the effect of inhaled corticosteroids on this balance in mild stable asthmatics. Included in the study were 30 mild asthmatic patients (11 male, 19 female, mean age (year) ± SD: 35.1 ± 9.7) and 26 healthy adults (7 male, 19 female, mean age (year) ± SD: 40.8 ± 13.3). In all study groups, the peripheral venous blood samples were taken for plasma malonyldialdehyde (MDA), a parameter of lipid peroxidation caused by the oxidants, and erythrocyte superoxide dismutase (SOD), an antioxidant enzyme. The mean plasma MDA level was lower in the asthmatic group (5.7 ± 1.2 nmol/ml) than in the healthy group (6.3 ± 1.7 nmol/ml); and the mean erythrocyte SOD level was higher in asthmatic group (1086.4 ± 247.4 U/gHb) than in the healthy group (1028.0 ± 230.0 U/gHb). However, there were no significant differences in measurements of both plasma MDA levels and erythrocyte SOD enzyme activities between the groups (respectively, p = 0.1 and p = 0.4). When asthmatic patients were divided into subgroups as inhaled steroid user and no inhaled steroid user, no significant differences were observed in the measurements of either plasma MDA level or erythrocyte SOD enzyme activity between the mentioned subgroups. According to the results of our study, we can say that oxidant-antioxidant balance is not significantly affected in mild asthmatics or measurement of plasma level of MDA and erythrocyte SOD enzyme activity is not sensitive to the oxidant-antioxidant balance in mild asthmatics.     

冠心病介入术后氧自由基的生成及其对脂质过氧化和纤溶的影响

目的:探讨冠心病介入治疗术后氧自由基的生成及其对患者体内脂质过氧化和纤溶状况的影响。方法:48例接受经皮冠脉介入治疗(PCI)术的冠心病患者分别于术前,术后即刻、30 min、1 h、24 h和一周采用ELISA法测定血浆中丙二醛、D-二聚体、血管假性血友病因子相关抗原(vWF Ag)浓度。结果:PCI术后短时间内(0～24 h)血浆中丙二醛、D-二聚体,vWFAg水平均明显升高(P<0．05)。结论:PCI术后短时间内即有大量的氧自由基生成,凝血系统的激活和继发性纤溶功能亢进。     

双歧杆菌对D-半乳糖致衰老小鼠的抗衰老作用

目的观察双歧杆菌对D-半乳糖所致亚急性衰老小鼠血液中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和丙二醛（MDA）含量的影响。方法小鼠颈背部皮下注射D-半乳糖建立亚急性老年模型，用双歧杆菌液拌少量小鼠饲料喂饲小鼠，实验前后取血检测血中s0D、GSH-Px及MDA值进行比较。结果双歧杆菌明显提高小鼠全血SOD含量（P〈0．01）和GSH-Px含量（P〈0．05），明显降低小鼠全血GSH-Px含量。结论双歧杆菌具有明显的抗衰老作用。     

A Study on the Effect of Ethanol Extract of Radix Rhapontici on Erythrocyte Immune Function in Rats

This paper mainly studied the effect of ethanol extract of Radix rhapontici on erythrocyte immune function in SD rats with acute blood stasis. The methods used the effect on erythrocyte immune function. After intragastric administration of suspension of ethanol extract of Radix rhapontici to SD rats for 3 weeks, on the 21st day from intragastric administration, SD rats were made into blood stasis model and bloods were collected to determine the C3b, C3bRR, RFIR, and RFER in erythrocyte immune function. Meanwhile, serum total antioxidant activity (TAA), superoxide dismutase (SOD) activity, and serum malondialdehyde (MDA) level of rats were determined, and experimental results were analysed with analysis of variance and Q test. The results showed that the ethanol extract of Radix rhapontici had a very good effect on enhancement of erythrocyte immune function in SD rats.     

Short exposure of albumin to high concentrations of malondialdehyde does not mimic physiological conditions

Malondialdehyde (MDA), a major lipid peroxidation product, spontaneously binds to, and modifies proteins. In vivo, proteins are physiologically exposed to micromolar MDA concentrations for long periods. In order to mimic this process in vitro, protein modification is often performed by short exposure to millimolar MDA concentrations, also in order to generate antigenic structures for antibody production.     

Protective effects of melatonin against spinal cord injury induced oxidative damage in rat kidney: A morphological and biochemical study

Spinal cord injury (SCI) induced oxidative stress affects multiple organ systems including the kidney. We studied the possible protective effects of melatonin on SCI-induced oxidative damage in renal tissues of rats. Wistar albino rats (n = 24) were exposed to SCI and divided into vehicle- or melatonin-treated SCI groups. Melatonin was administred intraperitoneally at a dose of 10 mg/kg for seven days. Renal tissues were investigated by light and electron microscopy. Furthermore, tissue malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and superoxide dismutase (SOD) activities were also determined. In the vehicle-treated SCI group, the renal histology was disturbed compared to controls, whereas the melatonin-treated SCI group showed significantly reduced degeneration of renal tissue as seen by both light and electron microscopy. MDA levels, MPO and SOD activities were increased and GSH levels were decreased in the vehicle-treated SCI group compared to controls. On the other hand, decreased MDA levels and MPO activities and increased GSH levels were observed in the melatonin-treated SCI group compared to vehicle-treated SCI group. These results showed that experimentally induced SCI caused oxidative stress in the rat kidney, whereas melatonin treatment reduced oxidative stress, suggesting that it may be used as a complementary therapy of renal problems occurring following SCI.     

Mass drug administration with azithromycin for trachoma elimination and the population structure of Streptococcus pneumoniae in the nasopharynx

ObjectiveMass drug administration (MDA) with azithromycin for trachoma elimination reduces nasopharyngeal carriage of Streptococcus pneumoniae in the short term. We evaluated S. pneumoniae carried in the nasopharynx before and after a round of azithromycin MDA to determine whether MDA was associated with changes in pneumococcal population structure and resistance.MethodsWe analysed 514 pneumococcal whole genomes randomly selected from nasopharyngeal samples collected in two Gambian villages that received three annual rounds of MDA for trachoma elimination. The 514 samples represented 293 participants, of which 75% were children aged 0–9 years, isolated during three cross-sectional surveys (CSSs) conducted before the third round of MDA (CSS-1) and at 1 (CSS-2) and 6 (CSS-3) months after MDA. Bayesian Analysis of Population Structure (BAPS) was used to cluster related isolates by capturing variation in the core genome. Serotype and multilocus sequence type were inferred from the genotype. Antimicrobial resistance determinants were identified from assemblies, including known macrolide resistance genes.ResultsTwenty-seven BAPS clusters were assigned. These consisted of 81 sequence types (STs). Two BAPS clusters not observed in CSS-1 (n = 109) or CSS-2 (n = 69), increased in frequency in CSS-3 (n = 126); BAPS20 (8.73%, p 0.016) and BAPS22 (7.14%, p 0.032) but were not associated with antimicrobial resistance. Macrolide resistance within BAPS17 increased after treatment (CSS-1 n = 0/6, CSS-2/3 n = 5/5, p 0.002) and was carried on a mobile transposable element that also conferred resistance to tetracycline.DiscussionLimited changes in pneumococcal population structure were observed after the third round of MDA, suggesting treatment had little effect on the circulating lineages. An increase in macrolide resistance within one BAPS highlights the need for antimicrobial resistance surveillance in treated villages.