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.     

Dietary and herbal supplements use among patients hospitalized in internal medicine departments

ObjectivesTo assess consumption of dietary and herbal supplements (DHS) among patients in internal medicine departments and determine whether such use is documented in their medical files.Methods267 patients from three internal medicine departments of an academic medical center in Haifa, Israel were assessed prospectively with questionnaires about their DHS use in the month preceding hospitalization. DHS were categorized into vitamins & minerals, herbal supplements and others. Further data was then collected from patients' medical records on socio-demographic and medical characteristics, as well as documentation of DHS use.Results123 patients (50.6 %) used DHS on a daily basis. Most of them (53.7 %) were using more than one DHS. DHS use was more prevalent in older (OR = 1.02 [1.001–1.036], p = 0.034) and educated (OR = 0.482 [0.252-0.923], p = 0.028) patients. Vitamins & minerals were used mainly to enhance vitality and address laboratory abnormalities, whereas herbal supplements were used mainly for gastrointestinal problems (p < 0.001). DHS use was reported to the physicians by 42 % of the patients, mostly at the patients’ initiative [92 (82.1 %), p < 0.001)]. Vitamins and minerals were the most reported category of DHS (94 (57.3 %), p < 0.001). The use of DHS was reported to physicians for 112 DHS (41.8 %) but only 32 DHS (11.9 %) were documented in their medical files. The documentation of vitamins and minerals was significantly higher compared to herbal supplements documentation (29 (17.7 %) & 3 (2.9 %) respectively, P < 0.001).ConclusionsDHS are commonly used by patients hospitalized in the internal medicine departments. Many patients do not report such use to the physicians, and more strikingly, physicians do not document DHS use in patient medical files. This communication gap may have serious medico-legal ramifications due to DHS side effects and DHS interactions with other DHS and with conventional drugs.     

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.     

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.     

2-乙氧基乙醇急性染毒大鼠血清和睾丸某些抗氧化指标的变化

目的 观察2-乙氧基乙醇(2-Ethoxythanol,EE)急性染毒对SD大鼠血清和睾丸某些抗氧化指标的变化，探讨EE致睾丸损伤的可能机制。方法 选择健康雄性SD大鼠，体重180-220g。随机分为对照组、EE800、1600和3200mg／kg组4组，每组24只。采取一次性灌胃染毒。于灌胃后12、24、48和72h，将各组动物随机处死6只，留取动物血液、睾丸，制备血清和睾丸匀浆，测定血清和睾丸匀浆脂质过氧化物(LPO)水平、超氧化物歧化酶(SOD)活性、过氧化氢酶(CAT)活性，以及血清铜蓝蛋白(CP)活性。结果 与对照组比较，各染毒组睾／体比明显下降(P＜0.05)，睾丸匀浆LPO水平和血清CP活性增高。染毒12、24h，血清CAT、睾丸匀浆CAT和SOD活性增高，而染毒48、72h后，血清CAT、睾丸匀浆CAT和SOD活性显著降低(P＜0.05)。EE各染毒组血清LPO水平和SOD活性变化不明显。结论 推测EE毒作用的靶器官可能是睾丸，睾丸抗氧化功能的改变是EE致睾丸毒性的可能机制。     

Effects of N-acetylcysteine on bacterial clearance

Abstract. The aim of this study was to investigate whether the oxygen radical scavenger N -acetylcysteine ( N -AC) impairs bacterial clearance, thus predisposing the host to increased risk of disease. Blood clearance of Escherichia coli and organ colonization were investigated in anaesthetized rabbits after pretreatment with N -AC (250 mg kg^-1 body weight, n = 16) and in sham-operated animals ( n = 12). To enable quantification of the clearance process, defined numbers of exogenous E. coli [1.3 times 108 colony-forming units (CFUs)] were injected intravenously. Parameters monitored were kinetics of bacterial elimination from the blood, and polymorphonuclear leucocyte (PMN) oxidative burst activity. Samples of liver, kidney, spleen and lung were collected for bacterial counts. Compared with controls, pretreatment with N -AC resulted in delayed bacterial elimination from blood and higher organ colonization with increased numbers of E. coli in liver, lung and kidney ( P < 0.05). N -AC treatment was associated with a suppressed PMN oxidative burst activity. Impaired bacterial clearance and enhanced organ colonization in N -AC-treated animals correlated with reduced oxidative burst activity, suggesting impaired granulocyte-dependent bacterial killing due to N -AC application.