Protective activities of ellagic acid and urolithins against kidney toxicity of environmental pollutants: A review

Oxidative stress and inflammation are two possible mechanisms related to nephrotoxicity caused by environmental pollutants. Ellagic acid, a powerful antioxidant phytochemical, may have great relevance in mitigating pollutant-induced nephrotoxicity and preventing the progression of kidney disease. This review discusses the latest findings on the protective effects of ellagic acid, its metabolic derivatives, the urolithins, against kidney toxicity caused by heavy metals, pesticides, mycotoxins, and organic air pollutants. We describe the chelating, antioxidant, anti-inflammatory, antifibrotic, antiautophagic, and antiapoptotic properties of ellagic acid to attenuate nephrotoxicity. Furthermore, we present the molecular targets and signaling pathways that are regulated by these antioxidants, and suggest some others that should be explored. Nevertheless, the number of reports is still limited to establish the efficacy of ellagic acid against kidney damage induced by environmental pollutants. Therefore, additional preclinical studies on this topic are required, as well as the development of well-designed clinical trials.     

Associations of HLA and drug-metabolizing enzyme genes in co-trimoxazole-induced severe cutaneous adverse reactions

Co-trimoxazole is mainly used as a first-line drug for treatment and prophylaxis against Pneumocystis jiroveci pneumonia. This drug, however, has been reported as the most common causative drug for severe cutaneous adverse reactions (SCARs). This study aimed to extensively elucidate the associations between genetic polymorphisms of HLA class I and genes involved in bioactivation and detoxification of co-trimoxazole on co-trimoxazole-induced SCARS in a large sample size and well-defined Thai SCARs patients. A total of 67 patients with co-trimoxazole-induced SCARs, consisting of 51 SJS/TEN patients and 16 DRESS patients, and 91 co-trimoxazole tolerant controls were enrolled in the study. The results clearly demonstrated that the HLA-B¹13:01 allele was significantly associated with co-trimoxazole-induced SCARs, especially with DRESS (OR = 8.44, 95% CI = 2.66–26.77, P = 2.94 × 10⁻⁴, Pc = 0.0126). Moreover, the HLA-C¹08:01 allele was significantly associated with co-trimoxazole-induced SJS/TEN in the HIV/AIDS patients with an OR of 8.51 (95% CI = 2.18–33.14, P = 8.60 × 10⁻⁴, Pc = 0.0241). None of the genes involved in the bioactivation and detoxification of co-trimoxazole investigated in this study play any major role in the development of all phenotypes of SCARs.     

Curcumin attenuates spatial memory impairment by anti-oxidative,anti-apoptosis,and anti-inflammatory mechanism against methamphetamine neurotoxicity in male Wistar rats: Histological and biochemical changes

ObjectiveMethamphetamine is used extensively around the world as a psychostimulant. The complications related to methamphetamine include methamphetamine-induced neurotoxicity, mainly involving intraneuronal processes, such as oxidative stress and excitotoxicity. Curcumin is effective against neuronal injury due to its antioxidant, anti-inflammatory effects. In this study, we examined the protective effects of curcumin against methamphetamine neurotoxicity.MethodsSixty male Wistar rats were divided into the following groups: control (n = 12), DMSO (n = 12), methamphetamine (n = 12), and methamphetamine + curcumin (100 and 200 mg/kg, respectively, intraperitoneal [IP]; n = 12). Neurotoxicity was induced by 40 mg/kg of methamphetamine administrated through 4 injections (4 × 10 mg/kg, q2h, IP). Curcumin (100 and 200 mg/kg) was administered at 7 days after the last methamphetamine injection. By using a Morris water maze task, the hippocampus-dependent memory and spatial learning were evaluated 1 day after the last curcumin injection. Then, the animal brains were isolated for biochemical measurements, as well as glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1(Iba-1) and caspase-3 immunohistochemical staining.ResultsThe current study demonstrated that administration of curcumin significantly attenuates spatial memory impairment (P < 0.01) following methamphetamine neurotoxicity. Curcumin caused a significant increase in the levels of superoxide dismutase and glutathione peroxidase (P < 0.05). However, it decreased tumor necrosis factor (TNF-α) (P < 0.05) and malondialdehyde (P < 0.01) levels as compared to the methamphetamine group. Also, curcumin significantly reduced Iba-1 (P < 0. 01), GFAP and caspase-3 positive cells in the hippocampus (P < 0.001).ConclusionCurcumin exerted neuroprotective effects on methamphetamine neurotoxicity because of its antioxidant and anti-inflammatory effect.     

我院药物代谢酶和药物作用靶点基因检测与精准药学服务实践与总结

目的回顾我院药物代谢酶和药物作用靶点相关基因检测与精准药学服务实践过程,总结经验,与同行分享。方法从准备工作、相关检测项目的确定,学术推广、项目优化和开展情况等方面详细阐述我院基因检测开展过程与精准药学服务情况。结果根据临床需求,我院已开展了以心脑血管药和抗精神病药为主的27种药物,26项检测,2018年全年位1587名患者提供个体化用药建议,受到临床医生和患者欢迎。结论基于代谢酶和药物作用靶点相关基因检测的个体化用药建议是临床药师参与精准治疗的重要途径,有助于医生和药师之间的沟通,有利于提高药学服务水平。     

Extracellular Enzyme Activities by Basidiobolus and Conidiobolus Isolates on Solid Media./Extrazelluläre Enzymaktivitäten bei Basidiobolus- und Condiobolus-Isólaten auf festen Medien

Summary: Fifty-seven isolates of Basidiobolus from reptiles and amphibians, and 7 other obtained from the American Type Culture Collection (ATCC) in Maryland were studied for their extracellular enzyme activities on solid media. The Conidiobolus isolates studied included 4 recovered from Nigerian soil and additional 4 obtained from the ATCC All these isolates produced active extracellular lipase and protease and failed to exhibit amylase, deoxyribonuclease and ribonuclease activities. The significance of the findings is discussed.
Zusammenfassung: Fünfundsiebzig Basidiobolus-Isolate aus Reptilien und Amphibien und sieben weitere aus der American Type Culture Collection (ATCC) in Maryland wurden auf Aktivtäten extrazellulärer Enzyme auf festen Medien untersucht Die untersuchten Conidiobolus-Isolate schlossen vier aus nigerianischen Böden und vier weitere aus der ATCC ein. Alle Isolate zeigten extrazellulär Lipase- und Proteaseaktivität Amylase-, Desoxyribonuclease- und Ribonucleaseaktivität war jedoch nicht nachzuweisen. Die Bedeutung dieser Befunde wird diskutiert.     

新生儿窒息后血糖,血气,心肌酶活性测定及其相关因素分析

目的：探讨新生儿窒息后血糖，血气，心肌酶（谷草转氨酶，磷酸肌酸激酶及乳酸氢酶）的变化及其相关性。方法；血糖采用微量血糖仪测定，血气用足跟动脉化毛细血管法，心肌酶采用酶偶联连续监测，相关分析采用多元线性回归法。结果：低血糖８例，高血糖３例；３６例均存在着不同程度的低氧血症和混合性酸中毒；２２例心肌酶活性增高。血糖值与日龄呈负相关，与体温呈正相关，心肌酶活性男性高于女性，各酶之间有一定的相关性，但并非     

Distribution of glutathione and glutathione-related enzyme systems in mitochondria and cytosol of cultured cerebellar astrocytes and granule cells

The cellular and regional distribution of glutathione (GSH) and GSH-related enzyme systems involved in cellular defense against reactive oxygen species and electrophilic xenobiotics in the nervous system has been extensively studied. However, little is known about the subcellular distribution of GSH systems in brain tissue and cultured neural cells. The present study investigates the distribution of mitochondrial and cytosolic GSH and GSH-related enzymes in cultured cerebellar astrocytes and granule cells, and compares them with levels in the adult rat cerebellum. Cytosolic GSH levels and cytosolic activities of glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) in astrocytes were 57, 153, 245, and 92% higher than those found in granule cells, respectively. In contrast, granule cells contained significantly higher mitochondrial GSH levels than astrocytes. Granule cells also demonstrated comparable mitochondria/cytosolic concentrations of GSH and GR, GPX and GST activities to those observed in the cerebellar tissue, whereas ratios in astrocytes were markedly lower. Although in vitro treatments with 100 μM ethacrynic acid depleted both cytosolic and mitochondrial GSH in cultured astrocytes and granule cells in a time-dependent fashion, cellular GSH in granule cells was more resistant to the GSH-depleting agent than astrocytes. These results suggest that although GSH and GSH-related enzymes are abundant in cytosolic compartments of astrocytes, mitochondrial pools are relatively small. Since brain mitochondria are sites of significant hydrogen peroxide generation, the mitochondrial localization of GSH and its associated enzymes in neural cells provide important defenses against toxic oxygen species in the nervous system. Differences in subcellular distribution of GSH systems in individual neural cell types may provide a basis for selective cellular and/or subcellular expression of neurotoxicity.     

端粒酶活性检测在乳腺癌诊断中的意义

[目的 ]探讨细针穿刺乳腺肿瘤组织的端粒酶活性检测在乳腺癌诊断中的意义 .[方法 ]用聚合酶链反应 酶联免疫吸附测定法检测 79例术前乳腺肿瘤细针穿刺活检标本和大体标本的端粒酶活性 ,并与病理诊断进行比较 .[结果 ]乳腺癌 6 5例中穿刺组织端粒酶呈阳性的为 5 7例 ,阳性率为 88% ;大体组织端粒酶呈阳性的为 5 4例 ,阳性率为 83% .淋巴结转移者端粒酶活性高于无淋巴结转移者 .乳腺良性疾病 14例中端粒酶呈阳性的为 2例 ,阳性率为 14 % .[结论 ]术前乳腺肿瘤穿刺组织的端粒酶活性检测有利于乳腺肿瘤的早期诊断及鉴别诊断 .     

晶体心脏停搏液优于血液心脏停搏液对风湿性心脏病患者的心肌保护

目的比较血液心脏停搏液和晶体停搏液对风湿性心脏病患者心肌保护的效果,为临床选择提供依据。方法将75例择期手术的风湿性心脏病患者分为两组:血液心脏停搏液组(B-rh)和晶体心脏停搏液组(C-rh)。分别于术前1d,术后1,3,5,8d晨分别取静脉血,测定血清天门冬氨酸氨基转氨酶(AST),肌酸激酶(CK)及同工酶MB(CK-MB),乳酸脱氢酶(LDH)及同工酶1(LDH-1)。结果术前除B-rh的LDH略高于正常水平外其它心肌酶的测定结果均在正常范围;术后1d两组的心肌酶分别升高到术前的3~19倍(P<0.05);术后3d两组的CK-MB虽说已恢复到正常值,但五种心肌酶仍明显高于术前水平(P<0.05);术后5dC-rh的CK和CK-MB,B-rh的CK,CK-MB和AST与术前相比已无明显差别(P>0.05);术后8d两组的LDH与LDH-1仍未恢复正常(P<0.05)。两组间有显著差异的心肌酶释放均是B-rh的高。心肌酶的释放量与主动脉阻断时间(CCT)和体外循环时间(ECCT)呈良好的正相关。两组患者的年龄,体重和ECCT无明显差异(P>0.05),CCT以B-rh为短[(77.2±34.6)min比(61.7±26.7)min,P<0.05]。结论从心肌酶的释放来判断,晶体心脏停搏液优于血液心脏停搏液对风湿性心脏病患者的心肌保护效果。