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.     

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.     

明党参根中维生素及其水煎膏中无机元素的分析

目的:考察明党参根中营养元素的种类及含量,探讨其补益功效的物质基础.方法:采用高效液相色谱法、荧光分光光度法及扫描电子微量分析法,测定明党参根中维生素的含量和水煎膏中无机元素的含量.结果:明党参根含脂溶性维生素E、K分别为259.2、64.1μg/kg,水溶性维生素C、B1、B2分别为78.5、0.6、0.7 mg/kg.明党参水煎膏中含丰富的钾和钙离子.结论:明党参富含人体必需的有益元素,作为食用中药是有其物质基础的.     

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.     

Antioxidant and glutathione-related enzymatic activities in rat sciatic nerve

The present work tries to establish the antioxidant capacity of the peripheral nervous tissue of the rat, in terms of the enzymatic activities present in this tissue that either prevent the formation of activated species as the semiquinone radical (DT-diaphorase), protect against activated oxygen species (superoxide dismutase, glutathione peroxidase), conjugate natural toxic products or xenobiotics (glutathione S-transferases, especially the activity conjugating 4-hydroxy-nonenal), or complete the glutathione system metabolism (glutathione disulfide reductase, γ-glutamyl transpeptidase). All the activities studied are lower in this tissue than they are in liver, except for γ-glutamyl transpeptidase. The relevance of the results obtained and its possible relationship with different neuropathies is discussed. It is concluded that the peripheral nervous tissue is by far less protected than the liver against oxidative damage.     

Decreased serum ceruloplasmin concentration in aluminum welders exposed to ozone

Summary During an epidemiological survey on arc welders, serum copper and ceruloplasmin were determined in two groups of workers. One group consisted of aluminum welders who were divided into two groups: 13 welders working inside aluminum tanks (confined atmosphere) and 8 welders engaged in the production of vans for dump trucks (nonconfined atmosphere). The reference group consisted of 26 workers of the same plant who were not exposed to welding fumes. Ozone, the major pollutant in aluminum arc welding, was thought to be the principal factor in the significant decrease (P < 0.01) of mean ceruloplasmin in confined welders. This decrease in the level of ceruloplasmin was still within the reference values and was not linked to age or to tobacco consumption. We found a linear relationship between ceruloplasmin concentration and the cumulated worktime along the week. This effect could be a sign in the serum of a lung reaction against oxidant activity in this type occupational exposure.     

Cytotoxicity of propyl gallate and related compounds in rat hepatocytes

 The cytotoxic effects of propyl gallate (PG), its related gallates and gallic acid have been studied in freshly isolated rat hepatocytes. Addition of PG (0.5–2.0 mM) to hepatocyte suspension elicited concentration-dependent cell death accompanied by losses of intracellular ATP, adenine nucleotide pools, glutathione (GSH) and protein thiols. The rapid loss of intracellular ATP preceded the onset of cell death caused by PG. In the comparative toxic effects of PG and related gallates at concentration of 1 mM, octyl gallate (OG), dodecyl gallate (DG) and butyl gallate (BG) elicited an abrupt depletion of ATP, followed by an acute cell death. These gallates were more toxic than PG; the toxic effects of PG were similar to those of methyl gallate (MG) and ethyl gallate (EG). In mitochondria isolated from rat liver, PG caused a concentration-dependent increase in the rate of state 4 oxygen consumption, indicating an uncoupling effect. The rate of state 3 oxygen consumption was inhibited by OG and DG. According to the respiratory control index, the order of impairment potency to mitochondria was OG>BG, DG>PG>EG, MG>gallic acid. These results indicate that PG and related gallates are toxic to hepatocytes and that the acute cytotoxicity may be due to mitochondrial dysfunction. Received: 16 May 1994 / Accepted: 15 August 1994