Expression and inducibility of drug-metabolizing enzymes in preneoplastic and neoplastic lesions of rat liver during nitrosamine-induced hepatocarcinogenesis

The expression, inducibility, and regulation of four different cytochrome (cyt.) P-450 isoenzymes (PB₁, PB₂, MC₁, and MC₂) NADPH-cytochrome P-450 reductase, the glutathione transferases (GSTs) B and C and microsomal epoxide hydrolase (mEH_b) have been studied during nitrosamine-induced hepatocarcinogenesis using immunohistochemical techniques. The investigations revealed basic differences in the expression of the individual drug metabolizing enzymes in the course of neoplastic development. While the two GSTs and mEH_b were increased in all preneoplastic and benign neoplastic lesions, the levels of the distinct cyt. P-450 isoenzymes were characteristically different from each other. Following initial changes in the expression of these enzymes in early preneoplastic lesions (i. e., increase of cyt. P-450 PB₁ versus slight decrease of the other cyt. P-450 isoenzymes), a continuous reduction of all cyt. P-450 isoenzymes was observed during the further course of hepatocarcinogenesis. In progressed neoplastic nodules, all cyt. P-450-isoenzymes and NADPH cyt. P-450 reductase were decreased to varying extents.Treatment of animals with inducers of the monooxygenase system, such as phenobarbital, 3-methylcholanthrene and polychlorinated biphenyls, led to a rather heterogenous pattern of enzyme alterations in preneoplastic and neoplastic lesions. Following administration of phenobarbital, some islets responded to the same degree as the surrounding tissue, others were less or not at all inducible and a few of the lesions showed a prominent increase in cyt. P-450 PB₂ and NADPH-cyt. P-450 reductase levels. The interesting finding that these two enzymes always showed concurrent changes may be indicative of a common regulation. Similar to phenobarbital, an induction of cyt. P-450 isoenzymes within carcinogen-induced lesions was also observed following administration of 3-methyl-cholanthrene or polychlorinated biphenyls.The results demonstrate that drug-metabolizing enzymes are abnormally regulated in carcinogen-induced lesions. The multiplicity of enzyme deviations within individual lesions and especially the enzyme inducibility strongly suggest that the focal enzyme alterations result from genotoxic effects of the carcinogen on regulatory systems of a higher order rather than from mutational events in individual structural genes.Dedicated to Professor Dr. Herbert Remmer on the occasion of his 65th birthday     

CK7、CK18、CK5／6及P63在不同类型肺癌组织中的表达分析

目的探讨CK7、CK18、CK5／6及P63在各类型肺癌组织中的表达情况。方法对104例肺癌手术标本进行免疫组化分析,联合检测CK7、CK18、CK5／6及P63的表达,同时分析它们在不同类型肺癌中的表达情况。结果CK7在腺癌、腺鳞癌及大细胞癌中的阳性表达率分别为91．07％、85．71％及50．00％,在鳞癌和小细胞癌中无阳性表达。CK18在腺癌、腺鳞癌、小细胞癌及大细胞癌中的阳性表达率分别为96．43％、85．71％、100％及100％,在鳞癌中无阳性表达。CK5／6在鳞癌中的阳性表达率为100％,在腺癌、腺鳞癌、小细胞癌及大细胞癌中无阳性表达。P63在鳞癌和腺鳞癌中的阳性表达率分别为100％及14．29％,在腺癌、小细胞癌及大细胞癌中无阳性表达。结论CK7及CK18可用于肺腺癌诊断,CK5／6及P63可用于肺鳞癌诊断。同时,CK18还可用于肺小细胞癌及大细胞癌的诊断。     

Induction of preneoplastic rat liver lesions with an attenuated p53 response by low doses of diethylnitrosamine

Previous reports have documented an attenuated p53 response to DNA-damage in preneoplastic enzyme-altered foci (EAF). Data suggest that this alteration is an adaptation to genotoxic stress induced by carcinogens. Here, we have studied whether the altered p53 response in EAF can be related to acutely apoptotic or cytotoxic doses of the carcinogen diethylnitrosamine (DEN). Eight groups of rats received cumulative doses of 0.25, 0.5, 1.0 and 2.0 mmol DEN/kg, administered weekly for either 10 or 20 weeks. A ninth group received 3.0 mmol/kg for 10 weeks, which gave a supralinear EAF response. Twenty-four hours before sacrifice, all rats were given a challenge dose of DEN in order to induce a p53 response in hepatocytes. The numbers of p53-positive hepatocytes in EAF and in surrounding tissue were analyzed. Unexpectedly, all cumulative doses gave rise to p53-negative EAF and 20-week treatment gave larger EAF with fewer p53-positive hepatocytes than 10-week treatment. It was also observed that at the lowest doses, most EAF developed in midzonal areas. Similar results were obtained with aflatoxin B1. Single high doses of DEN induced p53 accumulation and apoptosis within 24 h, whereas lower doses did not. It is concluded that EAF with an attenuated p53 response can be induced by low doses of genotoxic compounds, not giving rise to acute apoptosis or necrosis. Instead, it is suggested that time is an important determinant for its development at low doses and that a delayed type of apoptosis might be important.     

18F-FLT PET/CT显像在恶性肿瘤诊断中的应用价值

目的 探讨3'-脱氧-3'-18F-氟代胸苷(18F-FLT)PET/CT显像在恶性肿瘤诊断中的应用价值.方法 对31例恶性肿瘤患者行18F-FLT PET/CT显像,分析18F-FLT PET/CT显像中病灶感兴趣区(ROI)最大标准摄取值(SUVmax)和平均标准摄取值(SUVmean)与肿瘤类型、病理类型和分期的关系.结果 18F-FLT PET/CT显像图像质量好,病灶显影清晰.31例共发现100处病灶18F-FLT高摄取,SUVmax为(5.20士2.79),SUVmean为(4.35士2.38);其中,肺癌患者淋巴结转移4处,SUVmax为(2.29士1.54),SUVmean为(1.72士1.09),较鼻咽癌组低(P<0.05);鼻咽癌不同病理类型间SUV值差异无统计学意义(P>0.05).结论 10F-FLT PET/CT显像能清晰显示鼻咽癌、肺癌、淋巴瘤、喉癌、肾盂癌原发病灶及转移病灶,有临床应用价值.     

How to increase the reactivity of [18F]fluoroethyl bromide: [18F]fluoroethylation of amine,phenol and amide functional groups with [18F]FEtBr, [18F]FEtBr/NaI and [18F]FEtOTf

[¹⁸F]Fluoroethyl bromide ([¹⁸F]FEtBr) is a useful synthetic precursor to synthesize ¹⁸F‐labeled compounds. However, the lower reactivity of [¹⁸F]FEtBr with amine, phenol and amide functional groups than that of [¹¹C]CH₃I partly limits its wide application in the synthesis of [¹⁸F]fluoroethylated compounds. The aim of this study was to increase the reactivity of [¹⁸F]FEtBr with various nucleophilic substrates for PET tracers containing amine, phenol and amide moieties. The present strategies included (1) adding NaI into the reaction mixture of [¹⁸F]FEtBr and substrate, where [¹⁸F]FEtI is reversibly formed and becomes more reactive; (2) converting [¹⁸F]FEtBr into much more reactive [¹⁸F]FEtOTf, similar to conversion of [¹¹C]CH₃I into [¹¹C]CH₃OTf. By these efforts, the [¹⁸F]fluoroethylation efficiency of various substrates containing amine, phenol and amide groups with [¹⁸F]FEtBr/NaI and [¹⁸F]FEtOTf was significantly improved, compared with the corresponding reaction efficiency with [¹⁸F]FEtBr. Copyright © 2003 John Wiley & Sons, Ltd.     

Sequential dietary exposure to aflatoxin B1 and fumonisin B1 in F344 rats increases liver preneoplastic changes indicative of a synergistic interaction

Dietary co-exposure to aflatoxin B1 (AFB1) and fumonisin B1 (FB1) and their interaction on hepatocellular carcinogenesis is of particular concern in toxicology and public health. In this study we evaluated the liver preneoplastic effects of single and sequential dietary exposure to AFB1 and FB1 in the F344 rat carcinogenesis model. Serum biochemical alterations, liver histopathological changes, and the formation of liver glutathione S transferase positive (GST-P+) foci were the major outcome parameters examined. Compared to the AFB1-only treatment, the FB1-only treatment induced less dysplasia, and more apoptosis and mitoses. Sequential AFB1 and FB1 treatment lead to increased numbers of dysplasia, apoptosis and foci of altered hepatocytes, as compared to either mycotoxin treatment alone. More importantly, sequential exposure to AFB1 and FB1 synergistically increased the numbers of liver GTP-P+ foci by approximately 7.3-and 12.9-fold and increased the mean sizes of GST-P+ foci by 6- and 7.5-fold, respectively, as compared to AFB1- or FB1-only treatment groups. In addition, liver ALT and AST levels were significantly increased after sequential treatment as compared to single treatment groups. The results demonstrate the interactive effect of dietary AFB1 and FB1 in inducing liver GST-P+ foci formation and provide information to model future intervention studies.     

盐酸氨溴索对慢性阻塞性肺疾病患者急性期血清白细胞介素8及白细胞介素18的影响

目的 研究盐酸氨溴索对慢性阻塞性肺疾病(COPD)急性加重期白细胞介素8(IL)-8、IL-18的影响.方法 选择2007年11月至2009年11月住院的慢性阻塞性肺疾病患者82例,入院时均为急性加重期,肺功能中度.完全随机分为观察组50例,对照组32例.观察组在常规治疗基础上加用盐酸氨溴索注射液30 mg+5%葡萄糖注射液250 ml静脉滴注,2次/d,疗程14 d;对照组仅给予常规治疗,疗程14 d.分别观察2组治疗前后血清IL-8、IL-18水平.结果 对照组及观察组治疗后IL-8、IL-18水平分别为(139.81±42.38)ng/L、(64.2±19.6)ng/L及(89.27±30.68)ng/L、(49.8±17.9)ng/L.2组治疗后血清IL-8、IL-18水平均低于治疗前,差异具有统计学意义(P＜0.05);观察组治疗后血清IL-8、IL-18水平低于对照组,差异具有统计学意义(P＜0.05).结论 盐酸氨溴索可以抑制COPD患者血清IL-8、IL-18的释放,可能有一定的肺保护和治疗作用.

Abstract：

Objective To study the effect of ambroxo1 on interleukin (IL)-8, IL-18 in chronic obstructive pulmonary disease (COPD). Methods Eighty-two patients with acute exacerbation of chsonic obstructive pulmonary disease (AECOPD) between 2007 and 2009 were enrolled, according to the guidelines for COPD treatment. All patients were in acute period with middle level lung dysfunction. They were divided into two groups: conventional therapy (n = 32 ), conventional and interferential therapy ( n = 50). The treatment group was given conventional therapy plus ambroxol for 14 days. The levels of IL-8,IL-18 in serum before-and-after therapy in two groups were observed. Results The level of IL-8, IL-18 in serum of two groups after therapy was lower than that before therapy (P ＜0.05). In the group of conventional plus interferential theraphy,the level of IL-8 ,IL-18 in serum after therapy were lower than that of conventional therapy ( P ＜ 0.05). Conclusion Ambroxol can inhibit the release of IL-8,IL-18 in serum of COPD patients.     

Methylated chrysin, a dimethoxy flavone, partially suppresses the development of liver preneoplastic lesions induced by N-Nitrosodiethylamine in rats

The modifying effect of chemically modified chrysin on formation of preneoplastic foci induced by N-nitrosodiethylamine (DEN) was investigated in male rats. Male Wistar rats were administered three intraperitoneal injections of DEN (200 mg/kg bodyweight) interspersed by 2 weeks with or without an oral dose of dimethoxy flavone (DMF 100 mg/kg bodyweight), 2 weeks after DEN initiation. The number of GST-Pi positive foci and proliferating cell nuclear antigen (PCNA)-positive cells were significantly suppressed by the administration of DMF. Real-time RT-PCR analysis revealed that DMF treatment increased mRNA expression levels of apoptotic proteins p53 and fas, cell cycle regulatory proteins chek 2, cdkn1a, rad 50, anti-inflammatory protein pparg whereas the mRNA expression levels of bcl-2 and prdx-2 were decreased compared to mRNA levels in DEN-treated group. Therefore, we propose that DMF partially suppresses the formation of preneoplastic lesions in rats following DEN exposure by regulating anti-inflammatory and apoptosis-promoting events and restoring the cellular redox balance altered by DEN.     

CD8阳性T细胞亚群在肺癌外周血的检测及分析

目的 检测肺癌患者外周血清中CD8⁺T细胞亚群CD28⁺及CD57⁺的表达程度,探讨其临床意义。 方法 合肥市第二人民医院经细胞学或病理学诊断为肺癌的初次治疗患者30例, TNM分期(UICC,第7版)Ⅲ期12例,Ⅳ期18例。病理类型腺癌15例,鳞癌8例,小细胞肺癌7例。流式细胞仪分别检测肺癌患者组治疗前后及健康对照组人群的血清中CD8⁺T细胞CD28⁺和CD57⁺的表达水平,分析该表达水平变化及与肺癌临床分期和病理学类型之间的关系。 结果 肺癌患者治疗前血清中CD28⁺T细胞亚群比例为(12.34±3.72)%,CD57⁺ T细胞亚群比例为(19.53±5.26)%。而健康对照组血清中CD28⁺T细胞亚群比例为(23.53±4.15)%,CD57⁺ T细胞亚群比例为(11.37±2.73)%,差异有统计学意义(P<0.05),该类指标与肿瘤病理类型无关,而随着不同临床分期增加,CD8⁺CD57⁺T细胞未见差异,而CD8⁺CD28⁺T细胞表达差异有统计学意义(P<0.05)。经两周期化疗后,缓解组(完全缓解+部分缓解)患者血清中CD28⁺、CD57⁺T细胞亚群比与健康对照组患者相比,差异无统计学意义(P>0.05),而未缓解组(稳定+进展)患者的CD28⁺、CD57⁺T细胞亚群比例分别为(10.62±2.74)%、(20.45±4.36)%.与健康对照组差异有统计学意义(P<0.05)。 结论 肺癌患者血清中CD8⁺CD28⁺T细胞表达较正常人群明显减低,而CD8⁺CD57⁺T细胞表达较正常人群明显升高,联合该两种T细胞亚群检测不仅可以了解肺癌患者免疫状况,同时可以评估肺癌患者预后,有一定临床应用价值。     

Enhancement of preneoplastic lesion yield by Chios Mastic Gum in a rat liver medium-term carcinogenesis bioassay

The mastic (Pistacia lentiscus var. chia) tree is native throughout the Mediterranean region and has long proved a source of food additives and medical treatments. To investigate the modifying effects of Chios Mastic Gum on rat liver carcinogenesis, 6-week-old male F344 rats were subjected to the established rat liver medium-term carcinogenesis bioassay (Ito-test). At the commencement, rats (groups 1-4) were intraperitoneally injected with 200 mg/kg body weight of diethylnitrosamine (DEN). After two weeks, mastic was added to CRF (Charles River Formula)-1 powdered basal diet at doses of 0, 0.01, 0.1 and 1% in groups 1-4, respectively. At week 3, all rats were underwent two-thirds partial hepatectomy. The experiment was terminated at week 8. As results show, liver weights were significantly increased in a mastic dose-dependent manner among groups 1-4. The numbers (/cm²) and the areas (mm²/cm²) of glutathione S-transferase placental form (GST-P)-positive cell foci (≥ 0.2 mm in diameter) were significantly increased in the DEN-1% group compared to the DEN-alone group, along with the average areas per foci and larger-sized foci (≥ 0.4 mm). 5-Bromo-2′-deoxyuridine (BrdU) + GST-P double-immunohistochemistry showed the highest BrdU-labeling indices within GST-P foci in the DEN-1% group. 8-hydroxydeoxyguanosine (8-OHdG) levels in liver DNA did not vary, while real-time quantitative polymerase chain reaction (PCR) analysis of livers revealed many up- or down-regulated genes in the DEN-1% group. In conclusion, this is the first report to display a promotion potential of Chios Mastic Gum on the formation of preneoplastic lesions in the established rat liver medium-term carcinogenesis bioassay.     

Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2

Repertaxin is a new non-competitive allosteric blocker of interleukin-8 (CXCL8/IL-8) receptors (CXCR1/R2), which by locking CXCR1/R2 in an inactive conformation prevents receptor signaling and human polymorphonuclear leukocyte (PMN) chemotaxis. Given the unique mode of action of repertaxin it was important to examine the ability of repertaxin to inhibit a wide range of biological activities induced by CXCL8 in human leukocytes. Our results show that repertaxin potently and selectively blocked PMN adhesion to fibrinogen and CD11b up-regulation induced by CXCL8. Reduction of CXCL8-mediated PMN adhesion by repertaxin was paralleled by inhibition of PMN activation including secondary and tertiary granule release and pro-inflammatory cytokine production, whereas PMN phagocytosis of Escherichia coli bacteria was unaffected. Repertaxin also selectively blocked CXCL8-induced T lymphocyte and natural killer (NK) cell migration. These data suggest that repertaxin is a potent and specific inhibitor of a wide range of CXCL8-mediated activities related to leukocyte recruitment and functional activation in inflammatory sites.     

慢性宫颈炎合并人乳头瘤病毒16/18型感染临床分析

目的研究慢性宫颈炎合并高危人乳头瘤病毒(HPV)16／18型的感染情况。方法宫颈细胞学正常并经病理证实的慢性宫颈炎患者151例，根据宫颈拭子HPV16／18检测结果分为HPV16／18( )组和HPV16／18(-)组，分析患者年龄、临床表现、阴道镜检查结果，并对全部病例予宫颈激光治疗。结果HPV16／18阳性21例，阳性率为13．91％，两组患者年龄、临床表现差异无显著意义，HPV( )组异常阴道镜图像多，经激光治疗半年后，宫颈光滑17例，占80．95％，HPV16／18转阴16例，转阴率为76．19％。结论对合并高危HPV感染的慢性宫颈炎患者予以治疗，去除病灶，对预防宫颈癌有积极意义。     

One-year chronic toxicity of madder color in F344 rats – Induction of preneoplastic/neoplastic lesions in the kidney and liver

To evaluate chronic toxicity of madder color (MC), a natural food colorant extracted from the roots of Rubia tinctorum L., F344 rats were fed diet containing 0%, 0.2%, 1.0% or 5.0% MC for 53 weeks. Hematological changes including anemia and serum biochemical alterations indicating hepatotoxicity were demonstrated at 5.0% in both sexes. Relative weights of the liver were significantly increased from 1.0% in both sexes, and those of the kidney were significantly increased from 1.0% in males and from 0.2% in females. Histopathologically, atypical renal tubule hyperplasias were increased at 1.0% or higher in both sexes in association with increase of cell proliferative activity in the tubules. A renal cell adenoma was observed in a male rat receiving 5.0% MC. In addition, glutathione S-transferase placental form-positive liver cell foci were significantly increased at 5.0% in both sexes. These results indicate that MC has chronic toxicity targeting kidney, liver and blood cells. Moreover, the results strongly suggest that MC may have the carcinogenic potential in the kidney and the liver.     

Use of 1,8‐bis‐(dimethylamino)‐naphthalene/H18F complex as new radiofluorinating agent

Radiopharmaceuticals containing an ¹⁸F label are of increasing interest due to their utilization in PET imaging. However, the bottleneck in these applications is the limited methods available for introduction of this radionuclide into biologically interesting molecules. In this work, we have evaluated a new radiofluorination method based on the properties of the complex between 1,8‐(dimethylamino)‐naphthalene ( PS ) and [¹⁸F]–HF. The results obtained on various model substrates suggest that, in some limited cases, this new procedure can be regarded as a possible alternative to the traditional nucleophilic route using K₂₂₂/K₂CO₃ in CH₃CN. Copyright © 2004 John Wiley & Sons, Ltd.     

吸烟及HPV16/18 感染对低度宫颈上皮内瘤自然消退的影响

目的宫颈上皮内瘤变(cervical intraepithelial neoplasias,CIN)是一组与宫颈浸润癌密切相关的癌前期病变的统称,包括宫颈不典型增生和宫颈原位癌,反映了宫颈癌发生中连续发展的过程,本研究探讨吸烟及HPV16/18感染与宫颈上皮内瘤变自然消退之间的关系。方法追踪2009年1月～2010年12月在长沙市三医院及长沙市妇幼保健院确诊为宫颈上皮内瘤变Ⅰ、Ⅱ期患者并在1年后复检者共385例,其中吸烟者98例,不吸烟者287例,高危HPV16/18感染者242例,无高危HPV16/18感染者143例。1年后复检385例患者中166例宫颈上皮内瘤变自然消退。对HPV16/18及吸烟对宫颈上皮瘤变转归的关系进行统计学分析。结果一年后385例CIN中166自然消退,非HPV16/18感染患者较HPV16/18感染患者有更高的宫颈上皮内瘤变自然消退率(60.8%vs32.6%),而其中吸烟的HPV16/18感染者宫颈上皮内瘤变自然消退率最低(27.1%)。结论Ⅰ、Ⅱ期宫颈上皮内瘤变在12月内可自然消退,HPV感染(HPV16/18)是宫颈上皮内瘤变持续的重要因素,吸烟可能促进HPV感染患者宫颈上皮内瘤变的持续存在。     

F18-FDG PET/CT显像在空回肠淋巴瘤诊断中的价值

目的 探讨F18-FDG PET/CT显像在空回肠淋巴瘤诊断中的价值.方法 回顾性分析我院近9年来42例CT或内镜检查发现空回肠肿块的患者,然后行F18-FDG PET/CT显像,将PET/CT显像的诊断结果与术后病理对照,探讨F18-FDG PET/CT显像诊断空回肠淋巴瘤的准确率、敏感性和特异性.结果 所有42例病例中,F18-FDG PET/CT显像诊断为空回肠淋巴瘤的38例,术后病理结果其中空回肠淋巴瘤34例,空肠腺癌1例,回肠恶性间质瘤2例,回肠急性溃疡病1例;F18-FDG PET/CT显像诊断为良性病变4例,其中良性间质瘤2例,克隆氏病1例,淋巴瘤1例;F18-FDG PET/CT显像对空回肠淋巴瘤诊断的准确率为88.09％,敏感性为97.14％,特异性为75.00％.结论 F18-FDG PET/CT显像对空回肠淋巴瘤诊断有较高的准确率和敏感性,优于单纯的CT检查,具有重要的临床价值.     

食管癌放疗前后~(18)F-FDGSPECT/CT符合线路显像的临床应用价值

目的研究食管癌放疗前后18F-脱氧葡萄糖(18F-fluorodeoxyglucose,18F-FDG)SPECT/CT符合线路显像的临床应用价值。方法对29例食管癌患者放疗前后行18F-FDG SPECT/CT符合线路显像,必要时放疗靶区根据治疗前18F-FDG SPECT/CT符合线路显像结果进行修正,全部患者均随访12个月并根据临床及影像学随访评价为局部控制或失败,分析肿瘤区域18F-FDG摄取情况的变化及其与疗效的关系。结果 62%(18/29)的患者放疗靶区需根据18F-FDG SPECT/CT符合线路显像结果进行修正,全部患者1年局部控制率为69.0%(20/29),放疗后肿瘤区域18F-FDG摄取明显低于放疗前(P<0.01)。结论 18F-FDG SPECT/CT符合线路显像可用于食管癌放疗靶区的确定、放疗后疗效的预测与随访,且较为经济、简便。     

Discovery of Imidazoquinolines with Toll-Like Receptor 7/8 Independent Cytokine Induction

Toll-like receptors (TLRs) are key targets in the design of immunomodulating agents for use as vaccine adjuvants and anticancer treatments. The imidazoquinolines, imiquimod and resiquimod, have been shown to activate TLR-7 and -8 which in turn induce cytokine production as part of the innate immune response. Herein, we report the synthesis and discovery of a C7-methoxycarbonyl derivative of imiquimod that stimulates cytokine production but is devoid of TLR-7/8 activity. Data is presented that shows this analog not only induces IL-12p40 and TNF production, similar to that of imiquimod and resiquimod, but greatly enhances the production of IL-1β, a key cytokine involved in activation of CD4 T cells. It is further demonstrated that TLR-7/8 activation can be recovered by the addition of a C2-alkyl substituent to this newly discovered analog. The results support the existence of an alternative mechanism of action by which imidazoquinolines can stimulate cytokine production.     

Thiol/disulfide homeostasis as a marker of oxidative stress in rosacea: a controlled spectrophotometric study

Background: Rosacea is the chronic inflammatory disease of the facial skin. Although its aetiology is not clear yet, inflammatory processes triggered by oxidative stress and oxidation of lipids have been suggested to play a role. While studies on the relationship between inflammation and oxidative stress are ongoing, thiol metabolism and its role in oxidative stress have also begun to be investigated. Thiols are among the key molecules of protein metabolism in the organism and they are the firstly consumed antioxidants in case of oxidative stress. Thiols regulate intracellular redox metabolism and protect keratinocytes against the results of oxidative alterations in the stratum corneum. There is a balance known as dynamic thiol/disulfide homeostasis between thiols and their oxidized forms; disulfides.

Aim: This study aimed to determine the effects of oxidative stress on protein metabolism in rosacea patients by investigating thiol/disulfide homeostasis using a newly developed and fully automated method. Determination of plasma thiol levels provides important clues regarding the extent of free radical-mediated oxidation of proteins causing damage in rosacea.

Methods: The study included 50 rosacea patients who were diagnosed clinically or histopathologically with rosacea and 42 age- and gender-matched healthy controls. Plasma levels of native thiol, total thiol, and disulfide were determined. The following ratios were calculated: disulfide/native thiol ratio, disulfide/total thiol ratio, and native thiol/total thiol ratio.

Results: The mean age was 41.8?±?10.5 in the rosacea patients (35 females) and 42.5?±?10.3?years in the control group (33 females). The mean disulfide level was found to be significantly higher in the rosacea patients than in the control group (23.4?±?5.5?µM/L and 17.3?±?6.2µM/L, respectively; p?p?Conclusion: In rosacea patients, the thiol/disulfide balance was observed to shift towards disulfides, which could be considered an indicator of oxidative stress in rosacea.