Bioavailability and metabolism of hexavalent chromium compounds †

Intratracheal instillation of ⁵¹CrCl₃ in anaesthetized rabbits resulted in partial absorption. In blood, the absorbed material was entirely confined to the plasma compartment. Only trace amounts were deposited in liver and kidney. By contrast, after similar application of Na, ⁵¹CrO₄ the bulk of blood radioactivity was present in red blood cells (RBC). Substantial deposition occurred in liver and kidneys. It is concluded that Cr(VI) may enter the body unreduced via the lung and is partially deposited in cells over a prolonged period of time.

Since chromium was accumulated in liver after administration of Cr(VI) we investigated the intracellular disposition of Cr(VI) in the isolated perfused liver. No significant sex differences in chromium distribution were observed. At the end of the experiments (1 h), 60% of the applied dose (312μg Cr/liver) was located in the cytosol, whilst 14% was in the mitochondria, 9% in the microsomal pellet and 2% was associated with the nuclei. Gel chromatography of the cytosolic compartment showed that the overwhelming part of chromium was eluted in fractions with an apparent molecular weight of 6,000 dalton. These fractions exhibited absorption maxima at 410nm and 548nm. It is concluded, that cytosolic reduction might be the main intracellular redox pathway for chromates. This view was confirmed by monitoring the reaction of Cr(VI) with GSH in vitro. GSH reduced Cr(VI) without further cofactors under formation of GSH‐chromium complexes, which possibly represent major intermediates in the metabolism of Cr(VI).     

水胺硫磷亚急性暴露对小鼠肝脏氧化应激的影响

为探讨水胺硫磷对小鼠肝脏损伤作用机制,设置0.11、1.08、2.16 mg·kg-13个低、中、高不同剂量组,以灌胃方式对昆明种小鼠进行染毒7 d后,测定小鼠肝脏组织超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)2种抗氧化酶的活性,以及抗氧化物质谷胱甘肽(GSH)和膜脂质过氧化物丙二醛(MDA)含量,同时观察肝脏的组织学变化。结果表明,除低剂量组外,中、高剂量组小鼠肝脏SOD和GSH-Px活性与对照组相比均受到显著抑制(P0.05),GSH的含量与对照组相比显著下降(P0.05),MDA含量与对照组相比却呈显著上升趋势(P0.01),同时各指标的变化均呈一定的剂量-效应关系。组织学观察显示中、高剂量组肝细胞出现明显水肿和坏死,肝窦狭窄甚至闭塞。结果表明氧化损伤可能是水胺硫磷致小鼠肝脏毒性损伤的作用机制之一。     

铬在小鼠体内的蓄积效应与毒性

铬的工业用途很广,主要用于金属加工、电镀、制革等行业,这些行业排放的三废导致了环境铬污染,对环境生态和人体健康造成危害。为探究铬对动物的毒性作用,选择昆明种纯系小白鼠作为受试生物,研究六价铬在小鼠体内的蓄积效应及毒性。结果显示,饮用水中一定浓度的六价铬(15~70 mg·L-1)可抑制小鼠体重的正常增长,染毒30 d后,小鼠肝脏和肾脏脏器系数下降,脾脏和脑的脏器系数提高;总铬含量在心脏和脾脏中增高,其他脏器中无明显蓄积效应;铬染毒组小鼠骨髓细胞活性氧水平提高,骨髓嗜多染红细胞微核率显著增高。结果表明,通过饮水摄入六价铬可造成小鼠肝肾损伤,心脏和脾脏内铬蓄积,并通过活性氧损伤效应破坏机体的遗传稳定性。     

Gender-based comparative toxicity of di-ethyl phthalate in Wistar rats

In recent years, the exposure of humans to phthalate esters through environmental contamination has increased. One among them is di-ethyl phthalate (DEP), which is used as a plastisizer for cellulose ester plastic films and sheets, solid rocket propellants, molded and extruded articles, as a component in insecticide sprays and various other substances, as well as in industrial applications. Release into the environment occurs primarily as a result of production and manufacturing of DEP and during the use and disposal of products containing DEP. Therefore, a study was undertaken to evaluate gender-specific toxicity of DEP in Wistar rats. Rats of both sexes, weighing 125–130?g, were administered 50?ppm (w/v) DEP in water ad libitum for a period of 180 days and were given normal diet. Control animals received normal diet and water ad libitum. During the treatment, rats were weighed every week and water consumption per day was measured. After the completion of treatment, liver weight?:?body weight^?1 ratio, liver weight, body weight^?1, liver and serum enzymes, and other biochemical parameters of liver and serum were assessed. It was observed that there was no significant change in body weight^?1, liver weight, liver weight?: body weight^?1 ratio, and water consumption in both sexes. There were significant increases in liver acid phosphatase (ACP) activity and kidney glutathione levels, and nonsignificant changes in liver alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), succinate dehydrogenase (SDH), and lactate dehydrogenase (LDH) activities in DEP-treated male rats, whereas in DEP-treated female rats the liver showed significant decrease in ALP and SDH and nonsignificant changes in AST, ALT, and LDH activities. Serum ACP and LDH levels in DEP-treated male rats were significantly decreased, and in the case of DEP-treated female rats, only serum LDH levels were significantly decreased. There was no significant change in serum ALP, AST, and SDH levels in DEP-treated male and female rats as compared to control rats. Histology of the livers of both male and female rats showed loss of hepatic architecture, degenerative changes in hepatocytes, and vacuolation in hepatocytes in both the centrilobular and periportal areas. It can be concluded from this study that prolonged exposure to DEP at 50?ppm levels can be harmful to animals and humans. This is evident from the present study as certain significant changes in enzyme activities in the liver, serum, and histological alterations in liver were observed.     

Tissue-specific stress and hepatic DNA damage in Pelteobagrus fulvidraco caused by low concentrations of cadmium

Physiological stress and DNA damage in Pelteobagrus fulvidraco induced by continuous exposure to cadmium at concentrations of 170 and 1700 µg/L for up to 28 days was evaluated. The activities of acetylcholinesterase and monoamine oxidase in brain tissue, Na⁺-K⁺-ATPase and glutathione in gill tissue, and superoxide dismutase and catalase in liver tissue were measured. In studying random amplified polymorphic DNA to evaluate cadmium-induced hepatic genotoxicity, both the appearance of new bands and the disappearance of existing bands were observed, as well as increased levels of monoamine oxidase and Na⁺-K⁺-ATPase and decreased activities of antioxidant enzymes. The results suggest that continuous exposure to cadmium at the studied levels can induce biochemical and physiological changes and DNA damage in P. fulvidraco.     

Structure of and energy reserves in the liver of wild and cultured yellowtail flounder,<Emphasis Type="Italic"> Limanda ferruginea</Emphasis>

Knowledge of the structure and energy reserves, in the liver of commercially important fish species, is important in understanding metabolic processes and in assessing the impact of potential environmental physical and chemical stressors in both wild and cultured stocks. The present study investigated the microscopic morphology and histochemistry (total and neutral lipids, glycogen) of liver tissue of wild (3 ⁺) and cultured (1 ⁺) sexually immature female and male yellowtail flounder ( Limanda ferruginea Storer), sampled in late April 2001. Hepatosomatic indices [HSI: (liver weight/body weight-liver weight)×100] of cultured fish were significantly higher than those of wild fish. Females in the cultured group had significantly lower HSIs than males. The liver of both wild and cultured L. ferruginea was interspersed with pancreatic tissue. The main components of the liver tissue were irregular cords of hepatocytes arranged in tubules which surrounded vascular sinusoids. The hepatocytes contained an abundance of lipid, much of which appeared to be neutral lipids, in both sexes of the cultured fish. Total and neutral lipid droplets were larger, and the area occupied by these droplets was significantly greater in both cultured females and males compared to the wild fish, suggesting lipidosis in the cultured fish. In the cultured fish these differences were sex-dependent, the females having significantly more total and neutral lipids in hepatocytes than the males. This suggests a potentially greater storage capacity in females and/or a higher lipid metabolism in males. There were no statistically significant differences in glycogen content between the cultured and wild fish, or between the sexes in both sampling groups.     

Vitamin E-mediated protection on methomyl-induced alterations in rat liver

The present study was carried out to observe the possible beneficial effects of Vitamin E, a natural antioxidant on methomyl-induced biochemical and histological alterations in rat liver. To carry out the investigations, animals were segregated in four different groups. Animals in Group I served as normal controls. Animals in Group II were given single methomyl dose orally in water (9 mg kg^?1 b.wt). Animals in Group III were injected intraperitoneally with Vitamin E (50 mg kg^?1 b.wt) for 1 week on alternate days. Animals in Group IV were administered Vitamin E 1 week before subjecting them to methomyl treatment. Animals in all the groups were sacrificed 24 h after the end of treatments. Different biochemical estimations were carried out, which included estimation of aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), alkaline phosphatase (ALP) and acetylcholinesterase (AChE). Further, to examine the oxidative damage lipid peroxidation (LPO) and glutathione (GSH) levels as well as antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GSHPx), and glutathione-6-phosphate dehydrogenase were estimated in liver samples. AchE activity was inhibited significantly both in serum and liver following methomyl treatment. Administration of methomyl caused a significant increase in serum AST, ALT and ALP which indicated hepatic damage. LPO was found to be significantly increased, whereas GSH levels were decreased in the liver of methomyl-treated animals. The activities of SOD and catalase were significantly decreased whereas GST and GSHPx activities were found to be elevated significantly following methomyl treatment. No significant change in the enzyme activity of GR and glutathione-6-phosphatase dehydrogenase was observed after methomyl treatment. Vitamin E supplementation was able to attenuate appreciably the methomyl-induced changes in LPO levels along with SOD and GST activities. Histopathological studies following methomyl treatment revealed that hepatocytes, were not very well delineated and nuclei showed degenerative changes. Whereas, following Vitamin E supplementation in combined treatment group nuclei showing degenerative changes become less in number. The study, therefore, concludes that Vitamin E has a potential in mitigating most of the adverse effects induced by methomyl acute toxicity.     

Glucose and glycerol uptake by isolated zooxanthellae fromCassiopea xamachana: Transport mechanisms and regulation by host homogenate fractions

We investigated the mechanisms by which glycerol and glucose enter freshly isolated zooxanthellae (FIZ),Symbiodinium microadriaticum Freudenthal, of the mangrove jellyfish,Cassiopea xamachana Bigelow, and the specific sites of host factor interaction. Glucose entry into FIZ is accomplished by a Na⁺-dependent symport system driven by an electrochemical gradient generated via a Na⁺-K⁺ ATPase. Inhibition of glucose uptake by a low molecular weight fraction of host homogenates [mol. wt<2 kilodaltons (kD)] occurs through the interaction of a putative host factor with the carrier protein and not the ATPase. Glycerol entry is apparently accomplished by simple or facilitated diffusion and is not affected by host homogenate fractions.     

Interaction of short-term testosterone treatment with osmotic acclimation in the gilthead sea bream <Emphasis Type="Italic">Sparus auratus</Emphasis>

To assess the interaction between testosterone (T) treatment and acclimation to different salinities, seawater-acclimated gilthead sea bream (Sparus auratus) were implanted with slow-release coconut oil implants alone (control) or containing T (5 μg/g body mass). After 5 days, eight fish of control and T-treated groups were sampled. The same day, eight fish of each group were transferred to low salinity water (LSW, 6 ppt, hypoosmotic test), seawater (SW, 38 ppt, control test) and high salinity water (HSW, 55 ppt, hyperosmotic test) and sampled 9 days later. Gill Na⁺, K⁺-ATPase activity increased in HSW-acclimated fish with respect to SW- and LSW-acclimated fish in both control and T-treated groups. Kidney Na⁺, K⁺-ATPase activity was also enhanced in HSW-acclimated fish, but only in T-treated group. From a metabolic point of view, most of the changes observed can be attributed to the action of salinity and T treatment alone, since few interactions between T treatment and osmotic acclimation to different salinities were observed. Those interactions included in treated fish: in the liver, decreased capacity in using glucose in fish acclimated to extreme salinities; in the gills, decreased capacity in using amino acids in HSW; in the kidneys increased capacity in using amino acids in extreme salinities; and in the brain, decreased glycogen and acetoacetate levels of fish in LSW.     

Gas–liquid chromatography for fenvalerate residue analysis: alterations in the ionic concentration and associated adinosine triphosphatases in fish,Cirrhinus mrigala (hamilton)

In the present study, an attempt has been made to quantify the fenvalerate accumulated in different tissues (gill, muscle and liver) and observe changes involved in the levels of sodium, potassium and calcium ions and Na⁺–K⁺, Mg²⁺ and Ca²⁺ adenosine triphosphatase (ATPase) activities in the freshwater fish, Cirrhinus mrigala on short-term and long-term exposure to the median lethal and sublethal concentration of fenvalerate. Residue analysis using gas–liquid chromatography (GLC) technique revealed that fenvalerate accumulated in highest quantity in gill followed by liver and muscle under median lethal concentration (6?µg?L^?1). Whereas in sublethal concentration (0.6?µg?L^?1), muscle accumulated highest quantity followed by gill and liver, which might be due to the fact that fenvalerate is highly lyphophilic. The ion concentration and ATPase activity were found effected in fish exposed to lethal and sublethal concentrations of fenvalerate. Concentration of Na⁺, K⁺ and Ca²⁺ ions decreased in gill, muscle and liver on being exposed to median lethal concentration to a significant level. Whereas the changes were not highly pronounced at sub lethal level indicating low concentration of fenvalerate and its non-toxic effect at chronic exposure. Na⁺–K⁺, Mg²⁺ and Ca²⁺ ATPases activity were also found decreased in correspondence to the ionic change under median lethal and sub lethal concentrations in target tissues. This might have lead to behavioural changes and create wide-spread disturbance in the normal physiology, ultimately causing the death of the fish. The results suggest that in biomonitoring programmes, ions and associated ATPases can be a good diagnostic tool for fenvalerate toxicity.     

双酚A对小鼠肝脏和肾脏细胞的氧化损伤

为探究双酚A(BPA)的氧化毒性,分别以剂量为20、40和80mg·kg~(-1)·d~(-1)的BPA对雄性昆明小鼠灌胃处理1周,并测定了小鼠体内活性氧自由基(ROS)水平、还原型谷胱甘肽(GSH)含量、丙二醛(MDA)含量和DNA-蛋白质交联系数(DPC)。与对照组相比,各BPA暴露组小鼠肝脏和肾脏细胞中的ROS生成量、MDA含量和DPC系数均升高,而GSH含量下降(P<0.05或P<0.01)。ROS生成量、GSH含量和DPC系数均显示出剂量-效应关系。研究表明,BPA可扰乱小鼠肝脏和肾脏细胞的氧化应激平衡,诱导细胞氧化损伤。     

Sodium- and potassium-activated adenosine triphosphatase in the excretory organs of Sepia officinalis (Cephalopoda)

Sodium- and potassium-activated ATPase (Na⁺–K⁺-ATPase) has been demonstrated in excretory organs of Sepia officinalis, using a cytochemical procedure. In the renal appendages, both epithelia of the pancreatic appendages, the folded epithelium of the branchial heart appendage and the transport-active epithelium of the gill, the enzyme is localized exclusively in the basolateral cell membranes, i.e., the membranes of the basal labyrinth and the lateral plasma membranes. In addition, Na⁺–K⁺-ATPase is also located in the sarcolemma of the muscle fibres of the branchial heart. Distribution and localization of the enzyme is further substantiated by [³H]-ouabain autoradiography. The possible involvement of Na⁺–K⁺-ATPase in the excretion of ammonia and in ionic regulation in dibranchiate cephalopods is discussed.This study was supported by the Deutsche Forschungsgemeinschaft and is part of a doctoral dissertation     

内质网应激在PFOS致大鼠肝损伤中的作用

通过全氟辛烷磺酸(PFOS)28 d大鼠经口染毒评价PFOS肝损伤效应,探讨内质网应激在PFOS毒效应中的作用。Wistar大鼠随机分组,分别以0 mg·kg~(-1)、5 mg·kg~(-1)和10 mg·kg~(-1)PFOS灌胃染毒28 d。HE染色观察大鼠肝脏形态改变。ELISA法测定各组丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)和淀粉酶(AMY)含量变化。紫外分光光度法测定肝组织匀浆中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性变化。RT-PCR检测肝脏内质网应激标志蛋白表达水平。结果表明,PFOS造成大鼠体重降低、肝重增高(P0.05),组织切片显示肝细胞出现脂质沉积。PFOS不同剂量组大鼠ALT随暴露浓度增加,分别为(50.96±10.02)U·L~(-1)、(71.73±11.55)U·L~(-1),显著高于对照组(P0.05),AST、ALP含量与对照组相比显著上升(P0.05),高剂量组AMY水平为(833.46±63.05)U·L~(-1),与对照组相比显著降低(P0.05)。GSH-Px和SOD水平随PFOS浓度增加出现了显著降低(P0.05),而MDA水平显著升高(P0.05)。内质网应激标志蛋白表达均较对照组显著上升(P0.05)。以上结果说明PFOS可导致大鼠肝细胞损伤,其机制可能与内质网应激调控有关。     

Toxicological studies of zinc oxide nanomaterials in rats

In this study, we have evaluated the ability of zinc oxide (ZnO) nanoparticles to induce pulmonary and extrapulmonary toxicities was examined in rats following intratracheal (IT) instillation. Lungs of rats were instilled IT with either phosphate-buffered saline (PBS)?+?1% Tween 80, ZnO nanoparticles, carbonyl iron or quartz particles at a dose of 1 or 5?mg?kg^?1 body weight. Following exposure, bronchoalveolar lavage (BAL) fluid, blood samples and organs including lung, liver, kidneys, heart, pancreas, and brain were collected at 24?h, 1 week, or 1 month of post instillation of nanoparticles and different parameters estimated to assess toxicity. BAL fluid was analyzed for lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) to assess pulmonary toxicity. Exposures to ZnO or quartz particles produced transient dose-dependant increase in BAL fluid LDH and ALP activities at all post exposure periods. Blood samples were analyzed for the tissue damage biomarkers to assess extrapulmonary toxicity. Histopathological examination of lung, liver and kidneys revealed dose-dependent degeneration and necrosis which worsened at 1 week post-instillation periods but recovered at 1 month post instillation. Histopathological examination of rat pancreas, heart, and brain exposed to quartz or ZnO particles showed no marked changes. Data suggest the instillation of ZnO nanoparticles produced a greater pulmonary toxicity in rats comparable with quartz; and extrapulmonary toxicities of these ZnO nanoparticles might be due to translocation into liver and kidney.     

Ameliorated effects of garlic (Allium sativum) on biomarkers of subchronic acrylamide hepatotoxicity and brain toxicity in rats

Acrylamide (ACR) exerts its toxicity through stimulation of the oxidative stress; yet, its effect on neurotransmitter catabolic enzymes has not been elucidated. We investigated the effects of ACR exposure on brain and hepatic tissues antioxidant enzymes activities and different markers such as, acetylcholinesterase (AChE), nitric oxide (NO), monoamine oxidase (MAO), and lipid profile, and to evaluate the protective effects of garlic against ACR toxicity. Male Sprague-Dawley rats were exposed to ACR (1 mg kg^?1 body weight) with or without diet containing 1.5% of garlic powder for 40 days. ACR administration showed a decrease in AChE activity associated with an increase in MAO activity in both brain and hepatic tissues. In addition, ACR administration increased the lipid peroxidation and NO levels of both tissues while decreased the activities of glutathione (GSH), superoxide dismutase, and glutathione-S-transferase (GST). On the other hand, the activities of glutathione peroxidase (GPx) and catalase activities increased as a consequence of GSH depletion after ACR exposure. Finally, ACR exposure increased the brain and liver lipid profile of cholesterol, triglycerides and total lipid, while phospholipids level was decreased. Coadministration of garlic powder with ACR significantly attenuated oxidative stress, MAO activity, and inflammation in brain and hepatic tissues but did not ameliorate AChE activity. In conclusion, our results emphasized the role of garlic as a potential adjuvant therapy to prevent ACR neurotoxicity and hepatotoxicity.     

Evidence that the rotifer<Emphasis Type="Italic"> Brachionus plicatilis</Emphasis> is not an osmoconformer

The rotifer Brachionus plicatilis is euryhaline (growing between 2 and 97 ppt) and has previously been considered an osmoconformer. We suggest that B. plicatilis is an osmoregulator, exhibiting a pattern of Na⁺/K⁺ ATPase activity in response to salinity consistent with that of other osmoregulating euryhaline invertebrates. To examine salinity tolerance, growth rates between 5 and 60 ppt were determined. The activity of Na⁺/K⁺ ATPase was examined, over the same range of salinities, by measuring ATPase activity in rotifer homogenates in the presence and absence of a Na⁺/K⁺ ATPase inhibitor. Maximum specific growth rate (0.95 day^–1) occurred at 16 ppt, highest mean amictic eggs per female (1.41) occurred at 20 ppt, and both parameters decreased rapidly as salinity increased. Egg development time was constant with salinity at 0.92 days. The activity of Na⁺/K⁺ ATPase per milligram protein increased from 3.9 µmol h^–1 at 5 ppt to 6.8 µmol h^–1 at 50 ppt and accounted for 15 and 30% of total ATPase activity, respectively. We suggest that these observations are consistent with increasing stress at high salinities and the occurrence of a hypo-osmoregulatory response. Given the high ATP consumption of Na⁺/K⁺ ATPase at high salinities, it is possible that a proportion of the corresponding decreases in growth rate and egg production are a direct cost of regulation.Communicated by J.P. Thorpe, Port Erin     

立方体和八面体微/纳米氧化亚铜对大型水蚤(Daphnia magna)的氧化胁迫和生理损伤

为了实现特定的功能和应用,越来越多不同结构特性的纳米材料逐渐被人们精确合成。一些研究指出纳米材料的物理化学特性能够显著影响纳米材料对水生生物的毒性作用,但是对于不同特性的纳米氧化亚铜的毒性研究依然比较缺乏。本研究制备了2种不同形貌和结构的微/纳米氧化亚铜(micro/nano-Cu_2O)晶体,通过对大型水蚤(Daphnia magna)进行72 h的急性暴露实验,测定了大型水蚤体内还原型谷胱甘肽(GSH)的含量以及超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和钠/钾腺苷三磷酸酶(Na+/K+-ATPase)的活性变化。结果表明在2种不同特性的微/纳米氧化亚铜暴露体系中,大型水蚤体内Cu的积累量差别不大,但是不同结构的micro/nano-Cu_2O对大型水蚤抗氧化酶活性和钠/钾腺苷三磷酸酶活性影响存在差别。与立方体相比,八面体micro/nano-Cu_2O能够暴露更多的{111}面,并且其原子排列使其具有较高的表面能量,因此更容易在大型水蚤肠道内诱导产生活性氧(ROS)及溶出更多Cu2+,对大型水蚤产生更强的氧化胁迫和膜损伤。     

Adverse effects of chromium on amino acid levels in freshwater fish Clarias batrachus (Linn.)

Various heavy metals released into the rivers and lakes affect aquatic fauna including Clarias batrachus. Elevated levels of chromium (Cr) in aquatic organisms, especially fish, represent an ecological and human concern. Amino acid levels were estimated in five tissues (gills, liver, kidneys, muscle, and brain) of C. batrachus after 28 days of exposure to Cr. This study showed that Cr elevated levels of free amino acids in organs of fish C. batrachus, indicating a compensatory mechanism to counter sublethal metallic stress. Data suggest that the measurement of amino acids may serve as a biomarker for Cr toxicity in fish.     

4-硝基酚对大鼠肝脏的毒性及氧化损伤

研究环境内分泌干扰物4-硝基酚(4-nitrophenol,PNP)对大鼠肝脏功能的毒性作用及其对核因子相关因子-2(Nrf2)通路的影响.20只SD雄性大鼠随机分成4个组,分别为对照组、1、10和100 mg·kg-1体重PNP处理组,连续皮下注射28d,检测肝脏的结构变化、氧化损伤和Nrf2及其相关基因的表达情况.结果表明,与对照组相比,100 mg·kg-1PNP处理组大鼠的血清肝功能主要指标ALT、AST、AKP活性和TBIL含量显著性升高p＜005);100 mg·kg-1组肝脏GSH-PX、CAT和SOD活性显著性降低p＜005);大鼠肝脏中Nrf2及其下游基因NQOI和HO-1 mRNA表达水平在1mg·kg-1组显著升高(p＜0.05),10、100 mg·kg-1组有升高趋势;100 mg ·kg-1组肝脏显微和超微结构都发现有不同程度的损伤.结果提示,皮下注射1 mg·kg-1 PNP引起了大鼠肝脏氧化损伤,机体可能通过提高Nrf2及其相关基因mRNA的表达水平来抵抗PNP引起的肝脏损伤;皮下注射100 mg·kg-1 PNP改变了肝脏的正常生理功能,造成肝细胞超微结构病理损伤,引起肝脏毒性.     

镧、铈、钕对小鼠肝细胞核的氧化损伤作用

轻稀土元素进入生物体后主要累积于肝脏,进入肝细胞,分布于细胞核上.为探讨轻稀土元素对小鼠肝细胞核的氧化损伤作用,选用5周龄雄性封闭群(ICR)小鼠灌喂10、20和40 mg·kg-1的稀土元素镧(La)、铈(Ce)和钕(Nd),6周后测定小鼠肝细胞核中超氧化物岐化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(...