An LC-MS/MS method for creatine and creatinine analysis in paraquat-intoxicated patients

Abstract

A sudden increase in serum creatinine after paraquat intoxication has been reported in several clinical studies. However, this dramatic change of creatinine may be possibly due to an interconversion of creatine-creatinine in relation to paraquat toxicity. In order to investigate the creatine-creatinine relationship, a liquid chromatography tandem mass spectrometry in combination with electrospray ionization was developed and validated for simultaneous determination of creatine and creatinine in the serum. The chromatographic separation was achieved on a Gemini® C₆-Phenyl column with a gradient elution consisting of 0.1% formic acid in ultrapure water and methanol as the mobile phase. The method yielded suitable levels of specificity and selectivity, and calibration curves of creatine and creatinine in serum were linear over the concentration range of 0.5–200?µg mL^?1. The limit of quantification of both compounds was 0.5?µg mL^?1, and the method was accurate within the recovery range of 96.23–102.75%, indicating the robustness of the method. The method was successfully applied to toxicological samples from paraquat-intoxicated patients, and the concentrations of creatine and creatinine were quantified. High creatine concentrations in serum samples were observed which may lead to high serum creatinine despite normal kidney function as creatine is converted to creatinine in proportion to its concentration.     

Parental phenols exposure and spontaneous abortion in Chinese population residing in the middle and lower reaches of the Yangtze River

Widespread use of phenols has led to ubiquitous exposure to phenols. In experimental animals, phenols increased resorptions, reduced live litter size and fetal body weights. However, there are limited epidemiological evidences of the relationships between exposure to phenols and pregnancy outcomes. We evaluated the associations between parental urinary levels of various phenols and spontaneous abortion in a Chinese population residing in the middle and lower reaches of the Yangtze River. A case-control study was conducted that included 70 case couples with medically unexplained spontaneous abortion and 180 control couples who did not have a history of spontaneous abortion and had at least one living child. Both parental urinary phenols were measured by ultra-high performance liquid chromatography-tandem mass spectrometry including bisphenol A (BPA), benzophenone-3 (BP-3), 2,3,4-trichlorophenol (2,3,4-TCP), pentachlorophenol (PCP), 4-n-octylphenol (4-n-OP) and 4-n-nonylphenol (4-n-NP). Compared with the low exposure group, there was an increased risk of spontaneous abortion with high paternal urinary PCP concentration [odds ratio (OR) = 2.09, 95% Confidence Interval (CI), 1.05–4.14], and maternal exposure to 4-n-OP and alkylphenol(s) also significantly increased the risk of spontaneous abortion (OR = 2.21, 95% CI, 1.02–4.80; OR = 2.81, 95% CI, 1.39–5.65, respectively). Our study firstly provides the evidence that paternal PCP exposure, maternal 4-n-OP and alkylphenol(s) exposure are associated with spontaneous abortion in humans.     

Reversed association between levels of prostate specific antigen and levels of blood cadmium and urinary cadmium

Prostate cancer associated with cadmium exposure may indicate a link between prostate specific antigen (PSA) and levels of blood cadmium (BCd) and urinary cadmium (UCd). Thus, these associations were investigated. We recruited 295 men, 50 years of age and above from a health check-up program at a health center as subjects of the study. They completed a self-reported questionnaire and provided fasting samples of blood and urine for cadmium assay. The assay was performed using atomic absorption spectrophotometry. Blood samples were also collected for the assays of total cholesterol and high-density lipoprotein measures. The means of BCd and UCd increased with age and the means of all subjects were 1.19 ± 1.04 μg L⁻¹ and 1.37 ± 1.76 μg g⁻¹ creatinine, respectively. The PSA levels were positively associated with the lipid levels, but reversely associated with BCd and UCd levels. The multivariate logistic regression analysis showed that men with PSA ? 4.0 ng mL⁻¹ had an odds ratio (OR) of 0.4 (95% CI = 0.1-0.9) to have BCd > 0.49 μg L⁻¹, and an OR of 0.4 (95% CI = 0.2-1.0) to have UCd > 0.45 μg g⁻¹ creatinine. In conclusion, the PSA levels are reversely associated with BCd and UCd levels.     

燃煤型砷中毒病区尿砷甲基化代谢和砷致皮肤损伤危险度的关系初探

砷中毒具有特异的皮肤损伤特征。为了研究燃煤型砷中毒病区高砷暴露、人体甲基化代谢能力与皮肤损伤患病风险之间的关系,在陕南典型燃煤型砷中毒村进行了皮肤损伤诊断和流行病学调查,采集尿样并分析总砷及形态砷含量,同时计算了用于表征人体砷甲基化代谢能力的指标包括尿中无机砷、一甲基砷和二甲基砷占总砷的百分含量(i As%、MMA%、DMA%),以及一甲基化率(PMI=MMA/i As)和二甲基化率(SMI=DMA/MMA)。Logistic回归分析结果表明:尿总砷含量(UTAs)是砷致皮肤损伤的危险因素(OR=1.038,95%CI:1.003~1.073),二甲基砷百分含量和SMI是皮肤损伤的保护因素(OR=0.883,95%CI:0.798~0.976;OR=0.724,95%CI:0.535~0.978);且砷致皮肤损伤的危险度随砷暴露水平的增高和甲基化能力的降低而增大。     

A study of biochemical parameters among individuals residing in a fluoride endemic area in India

Fluoride (Fl) exerts an inhibitory effect on many metabolic enzymes of various tissues. A study was carried out among individuals residing in a Fl-affected area in India. The biochemical parameters including serum enzyme activities of alkaline phosphatase (ALKP), glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH), and serum creatinine (CRTN) were estimated in 259 subjects compared to 233 controls. The results showed that among the Fl-exposed population, ALKP and SGPT were significantly increased compared to control. The CRTN levels were also significantly increased compared to the control subjects. LDH levels were not markedly altered. Data suggest that Fl exposure affects renal and hepatic functions in endemic areas of India.     

Alterations in some renal parameters of rats induced by aqueous soil extracts

Soil ingestion can be an important route of exposure to contaminants present in the environment. This study examined the effects of exposure to contaminants in aqueous soil extracts from an industrial urban settlement in renal biochemical parameters of treated rats. Male Wistar rats were gavaged with an aqueous soil extract, from the municipality of Rio Grande, Southern Brazil. After exposure, plasma and urine concentrations and plasma protein were assessed compared to rats treated with aqueous soil from relatively unpolluted site (control soil). There was increase in plasma creatinine and total protein in urine, and a decreased glomerular filtration rate in treated rats compared to control. It is possible that Cd, Cr, As, Cu, Pb, Zn, and Ni analyzed in the soil samples and unidentified components may have provoked the observed changes in renal biochemistry of the exposed rat. This may suggest that exposure to contaminated soils can cause damage to the viscera in mammals and it is of public health importance.     

中国居民碘营养健康风险评估

我国碘元素的天然分布极不均匀,因此对地域差异缺乏考虑的全民食盐加碘政策(USI)并非碘缺乏病的最适宜的防控策略,甚至还增加了"碘过量"导致的潜在健康风险。近年来,中国卫生部多次调整食盐加碘政策,但亟需从健康风险评估的角度对该政策进行科学的论证和解读。通过解析全国碘缺乏病监测数据中8～10岁儿童尿碘浓度的数据,采用有阈值的剂量效应曲线,评价了中国居民碘营养健康状况,并计算出全国31个省级地区8～10岁儿童因碘过量导致的"亚临床甲状腺功能减低(亚甲减)"的发病率,最后利用5%基准剂量(benchmark dose,BMD),并结合我国居民膳食营养结构的调查结果,提出了考虑地域差异的分层次的食盐加碘量推荐值上限。研究表明,我国居民尿碘浓度分布有明显的区域性特征,尿碘浓度几何平均值和几何标准差分别为168.17和2.24μg·L-1,由于碘摄入过量导致的亚甲减发生率为4.00%。低水碘地区(水碘浓度低于150μg·L-1)的食盐加碘量推荐值上限为29.62mg·kg-1;中、高水碘地区(水碘浓度高于150μg·L-1)的居民通过非碘盐途径摄入的碘量已高于日可耐受最大摄入量,不宜再食用加碘食盐。这些结果基本支持了我国调整后的现行食盐加碘政策,即各地区根据当地人群实际碘营养水平,选定适合本地的食用盐加碘量。     

Determination of andrographolide sodium bisulfite in renal microdialysis fluid of rats and toxicokinetic study

Abstract

Andrographolide sodium bisulfite (ASB) widely used for intestinal infections and respiratory tract infections. It has been reported to frequently cause acute renal failure in clinical practice. The purpose of this study was to evaluate the nephrotoxicity and toxicokinetics in Sprague-Dawley rats after a single-dose injection of ASB administered at 100, 600, and 1000?mg/kg via intravenous tail injections. The concentrations in plasma and kidney microdialysates were analyzed by high-performance liquid chromatography. Blood urea nitrogen and creatinine levels in plasma were determined and toxicokinetic parameters were observed. In plasma and kidney, the elimination constant and clearance were decreased and the half-time was increased with increasing dose. Blood urea nitrogen and creatinine were positively correlated with ASB concentration indicating the potential for accumulation in kidney that can eventually lead to damage.