姜黄素改善丝裂霉素C导致的肾功能损伤

目的 探讨姜黄素对丝裂霉素C(MMC)导致的肾功能损伤的影响及作用机制.方法 制备人乳腺癌异种移植瘤裸鼠模型,2周后分别ip给予姜黄素100 mg·kg<'-1>,隔天1次,MMC 1,1.5和2 mg·kg<'-1>,隔5 d 1次;姜黄素+MMC组各药的剂量与频率与单独用药一致,实验持续4周.观察动物体质量和存活率...     

Plasma metallothionein antibody and cadmium-induced renal dysfunction in an occupational population in China.

It has been reported that anti-metallothionein (a metallothionein antibody) is present in the circulation of healthy subjects and in patients suffering from atopic dermatitis. The aim of this study was to investigate whether cadmium-induced renal dysfunction is related to the presence of the plasma metallothionein antibody (MT-Ab) in workers exposed to cadmium (Cd) occupationally. Plasma metallothionein antibody was determined by enzyme linked immunosorbent assay (ELISA) techniques, and both exposure assessment and risk assessment were conducted in cadmium-exposed workers in China. We demonstrate that there is a significantly increased prevalence of renal dysfunction with respect to the level of urinary cadmium in a dose-dependent manner. We found no significant correlations between the levels of MT-Ab and the external or internal exposure doses of cadmium (p > 0.05), but the levels of MT-Ab did correlate positively with two biomarkers of renal dysfunction-urinary beta2-microglobulin (UB2M; r = 0.218, p < 0.05) and N-acetyl-beta-D-glucosaminidase (UNAG; r = 0.302, p < 0.001)-in the cadmium-exposed workers. Workers who have high levels of MT-Ab display cadmium-induced tubular nephrotoxicity more frequently than those possessing low levels of MT-Ab; odds ratio (OR) 4.2; 95% confidence intervals 1.2-14.5 (p < 0.05). This study suggests that subjects that have higher MT-Ab levels more readily develop cadmium-induced renal dysfunction. Thus, the levels of plasma MT-Ab can be used as a biomarker of susceptibility to renal dysfunction in occupational cadmium exposure.     

环磷腺苷致严重过敏样反应及肾损害

1例71岁女性患者因甲状腺功能亢进性心脏病,给予环磷腺苷40 mg加入0.9%氯化钠注射液250 ml静脉滴注.用药5 min后.患者出现剧烈腰痛、心悸,30 min后出现双侧眼睑水肿、胸闷、呕吐.血压180～190/100～105 mm Hg(1 mm Hg=0.133 kPa),两下肺闻及湿哆音.肾功能检查:潜血(...     

Differential effects of the adenosine A1 receptor agonist adenosine amine congener on renal, femoral and carotid vascular conductance in preterm fetal sheep

1. Adenosine A(1) receptor activation is critical for endogenous neuroprotection from hypoxia-ischaemia, raising the possibility that treatment with A(1) receptor agonists may be an effective physiological protection strategy for vulnerable preterm infants. However, the A(1) receptor can mediate unwanted systemic effects, including vasoconstriction of the afferent glomerular arteriole. There is limited information on whether this occurs at doses that improve cerebral perfusion in the immature brain. 2. Therefore, in the present study, we examined whether infusion of the selective A(1) receptor agonist adenosine amine congener (ADAC) is associated with reduced renal perfusion in chronically instrumented preterm (0.7 gestation) fetal sheep. In the present study, ADAC was given in successive doses of 2.5, 5.0 and 15.0 microg, 45 min apart. 3. Treatment with ADAC was associated with a marked reduction in renal vascular conductance (and blood flow), whereas carotid conductance was increased and there was no significant effect on femoral conductance. In contrast with the stable effects of increasing ADAC dose on vascular conductance, there was a significant dose-related fall in fetal heart rate and blood pressure. 4. In conclusion, these short-term data support the concern that A(1) receptor agonist infusion can selectively impair renal perfusion, even at low doses.     

Adenosine receptor modulation of sympathetic neurotransmission in rat isolated kidney

In the present study we set out to define, using discriminatory agonists and antagonists, the adenosine receptors modulating sympathetic neurotransmission in the rat kidney. Isolated kidneys from male Wistar rats were perfused with modified Krebs-Henseleit buffer solution at constant flow. The neuronal noradrenaline stores were labeled with ³H-noradrenaline and the renal nerves stimulated electrically (2 Hz, 3 msec, 9 mA, during 20 sec at intervals of 6 min). ³H overflow was taken as an index of ³H-noradrenaline release. The A₁ receptor selective agonists N⁶-cyclopentyladenosine (CPA), N⁶-cyclohexyladenosine (CHA), and N⁶-[R(−)-1-phenyl-2-propyl]adenosine (R-PIA), and the mixed A₁/A_2A receptor agonists 5′-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CADO) inhibited evoked ³H outflow concentration-dependently. The selective A_2A receptor agonist 2-[p-(2-carboxyethyl)phenylethylamino]-5′-N-ethylcarboxamidoadenosine (CGS 21680), at concentrations selective for A_2A receptors, failed to modify ³H outflow, whereas at higher concentrations it induced inhibition. The rank order of potency of agonists, CPA > CHA = R-PIA > NECA > CADO >> CGS 21680, is typical for an interaction with the A₁ receptor. 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX), at concentrations selective for blockade of A₁ receptors, blocked concentration-dependently the inhibitory effects of CPA and NECA; no evidence of an increase in outflow was seen with NECA in the presence of DPCPX. The selective A_2A receptor antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazol[1,5-c] quinazoline-5-amine (CGS 15943) did not influence the agonist effects at concentrations interacting selectively with A_2A receptors but antagonized them concentration-dependently at higher, non-selective concentrations. Taken together, our data establish the presence of inhibitory adenosine A₁ receptors on the terminal sympathetic neurons of rat kidney. No evidence was obtained for the presence of functional A_2A receptors in this preparation. © 1996 Wiley-Liss, Inc.     

Endogenous adenosine inhibits excitatory transmission in the rat olfactory cortex slice

Excitatory neurotransmission in the rat olfactory cortex slice has been monitored by measuring the amplitude of the N-wave surface field potential evoked by stimulation of the lateral olfactory tract. Application of exogenous adenosine or aspartate depressed the N-wave amplitude and evoked synthesis of cyclic AMP. These effects were partially antagonized by theophylline and the reduction of amplitude of the N-wave was potentiated by dipyridamole. When the olfactory tract slice was stimulated, dipyridamole alone reduced the amplitude of the N-wave and increased levels of cyclic AMP, both effects being antagonized by theophylline. Exogenous adenosine significantly attenuated the K+-evoked release of [3H]D-aspartate by a mechanism insensitive to either theophylline or dipyridamole. It is concluded that synaptic activation of the olfactory cortex releases adenosine, possibly as the result of the actions of the transmitter candidate of the olfactory tract, aspartate, and that this causes sufficient adenosine to accumulate to depress excitatory transmission and elevate tissue levels of cyclic AMP although there is no positive evidence that these two effects are directly related.     

Effect of adenosine, adenosine triphosphate, adenosine deaminase, dipyridamole and aminophylline on acetylcholine release from electrically-stimulated brain slices

The effect of adenosine on release of acetylcholine (ACh) was investigated in slices of rat cortex perfused with Krebs solution, at rest and during electrical stimulation at frequencies between 0.2 and 20 Hz. Electrical stimulation brought about a linear increase in release of ACh. Adenosine, in concentrations ranging from 1 to 100 microM, reduced in a dose-dependent manner the release of ACh and was more active on the stimulated than on the resting release. However, the fractional reduction by adenosine of stimulated release of ACh did not vary with increasing stimulation rate. Adenosine triphosphate was less active than adenosine in reducing release of ACh. The inhibitory effect of adenosine was antagonized by aminophylline (0.5 mM) and did not occur when the stimulated release of ACh was enhanced by blocking muscarinic autoreceptors with atropine (15 nM). Aminophylline (0.1 and 0.5 mM) itself exerted a biphasic effect on release of ACh, increasing it at rest and during stimulation at low frequencies, and decreasing it at higher stimulation rates. The manipulation of endogenous adenosine concentrations by adding adenosine deaminase or diphyridamole, an inhibitor of adenosine uptake, had little effect on release of ACh. Dipyridamole, (4 microM), only significantly decreased release of ACh at the 20 Hz stimulation rate.     

Changes of serum adenosine deaminase activity induced by stress in rats

Rats were restrained for 4 h or for 4 h per day on three consecutive days and blood samples were obtained 30 min after their release. The adenosine deaminase (ADA) activity in the serum was measured by a micro-method with quantitation of the ammonia generated by ADA. Repeated restraint stress significantly (p<0·05) elevated serum ADA activity, while a single 4 h episode of restraint stress had no affect on this activity. It seems possible that the increase in ADA activity in the former case might have been related to the enhanced differentiation and maturation of suppressor T cells. To our knowledge, the present results are the first to demonstrate that serum ADA activity can be affected by stress. © 1998 John Wiley & Sons, Ltd.     

Response of isolated renal artery rings to adenosine and inosine

The responses to adenosine and its analog, inosine, were compared in isolated rings of canine small renal arteries (0.5–1.3 mm o.d.). The rings were not contracted prior to nucleoside administration in order to detect any contraction response due to the nucleoside itself. Relaxation responses were elicited by progressively increasing the nucleoside concentration in the bathing medium. The maximal response (R_max) was expressed as a percentage of the decrease in isometric tension. The ED50 for adenosine and inosine was 0.18 ± .002 μM and 202 ± 44 μM, respectively (P < 0.05) The R_max for inosine was significantly less (P < 0.05) than that for adenosine, with a mean ratio of adenosine R_max inosine R_max of 1.47 ± 0.2. The results of these experiments indicated that adenosine and inosine directly relax isolated small renal arterial rings, although the classic in situ renal response to adenosine is increased resistance. Also, the relaxing action of adenosine, but not inosine, is significantly attenuated by 10 μM aminophylline. Further, renal arterial rings exhibit a greater sensitivity to adenosine than that previously reported for canine coronary artery rings, while the response to inosine is virtually identical.     

Curcumin attenuation of acute adriamycin myocardial toxicity in rats

The protective effect of curcumin on acute adriamycin (ADR) myocardial toxicity was analysed in rats. ADR toxicity, induced by a single intraperitoneal injection (30 mg kg⁻¹), was revealed by elevated serum creatine kinase (CK) and lactate dehydrogenase (LDH). The level of the lipid peroxidation products, conjugated dienes and malondialdehyde, was markedly elevated by ADR. ADR caused a decrease in myocardial glutathione content and glutathione peroxidase activity. In contrast, cardiac catalase activity was increased in ADR rats. Curcumin treatment (200 mg kg⁻¹, seven days before and two days following ADR) significantly ameliorated the early manifestation of cardiotoxicity (ST segment elevation and an increase in heart rate) and prevented the rise in serum CK and LDH exerted by ADR. ADR rats that received curcumin displayed a significant inhibition of lipid peroxidation and augmentation of endogenous antioxidants. These results suggest that curcumin inhibits ADR cardiotoxicity and might serve as novel combination chemotherapeutic agent with ADR to limit free radical-mediated organ injury.     

Protective effects of FK453, a potent nonxanthine adenosine A1 receptor antagonist,on glycerol-induced acute renal failure in rats

The purpose of the present study was to examine the protective effect of FK453, (+)-(R)-1-[(E)-3-(2-phenylpyrazolo [1,5-a] pyridin-3-yl) acryloyl]-2-piperidine ethanol, a potent non-xanthine (adenosine A₁ receptor antagonist, on glycerol-induced acute renal failure (ARF) in rat in comparison with the effects of FR113452 (S-(-) enantiomer of FK453), 1,3-dipropyl-8-cyclopentyl-xanthine (adenosine A₁ receptor antagonist), theophylline (nonselective adenosine receptor antagonist), CGS15943 [1,2,4] triazolo [1,5-C] quinazolone, adenosine A_2A receptor antagonist), and typical diuretics (hydrochlorothiazide and furosemide). FK453 (1 and 10 mg/kg orally) significantly reduced serum creatinine and urea concentrations in 25% glycerol (10 ml/kg intramuscularly)-induced ARF by protective treatment. The effect was similar to that of 1,3-dipropyl-8-cyclopentyl-xanthine and theophylline. FR113452 and CGS15943 had little effect on serum creatinine and urea concentrations. In contrast, hydrochlorothiazide and furosemide increased serum creatinine and urea concentrations. FK453, hydrochlorothiazide, and furosemide did not have any effect on either serum creatinine or urea concentration in 25% glycerol-induced ARF by therapeutic treatment. In 50% glycerol (10 ml/kg im)-induced ARF, FK453 reduced serum creatinine and urea concentrations, and increased urine volume and creatinine clearance. The results of the present study showed that FK453, a potent nonxanthine adenosine A₁ receptor antagonist, ameliorated glycerol-induced ARF in the rat. The findings support the idea that adenosine is an important factor in the development of glycerol-induced ARF in the rat and that the protective effect of adenosine receptor antagonist is mediated via the adenosine A₁ receptor. Drug Dev. Res. 39:47–53 © 1997 Wiley-Liss, Inc.     

Benchmark dose estimation of urinary and blood cadmium as biomarkers of renal dysfunction among 40‐75‐year‐old non‐smoking women in rural areas of southwest China

This study evaluated the association between urinary cadmium (U‐Cd) and blood Cd (B‐Cd) and several biomarkers of renal dysfunction (α₁‐microglobulin [α₁‐MG], β₂‐microglobulin [β₂‐MG], N‐acetyl‐β‐d ‐glucosaminidase, metallothionein, retinol‐binding protein and microalbumin [mALB]) and identified the biomarker(s) that was most closely correlated with U‐Cd and B‐Cd among female residents in rural areas of southwest China. U‐Cd, creatinine (Cr), B‐Cd and the above‐mentioned six biomarkers in morning spot urine samples were measured from 288 randomly selected 40‐75‐year‐old non‐smoking women from non‐polluted areas and Cd‐polluted‐areas. The lower 95% confidence limit of the benchmark dose (BMD) corresponding to the 5% (BMDL₀₅) and 10% benchmark response (BMDL₁₀) was calculated with assumed cut‐off values of the 95th and 90th percentile. Among the investigated women, a significant positive association was found among mALB, β₂‐MG and U‐Cd as well as B‐Cd. By using the cut‐off value of the 95th percentile, the BMDL₀₅/BMDL₁₀ of U‐Cd and B‐Cd were 4.33/8.89 μg/g Cr for mALB and 1.35/2.77 μg/L for β₂‐MG, respectively. The BMDL₀₅/BMDL₁₀ of U‐Cd (B‐Cd) was 2.73/5.60 μg/g Cr (1.00/2.05 μg/L) for mALB, if the cut‐off value was set at the 90th percentile. Therefore, β₂‐MG and mALB in urine were good biomarkers for long‐term environmental Cd exposure assessment among the six biomarkers studied for the study pool in southwest China. Our findings may help us to understand the association between nephrotoxicity and Cd exposure, and aid in the decision‐making of authorities for environmental Cd pollution and public health.     

Transport of deoxycoformycin in human erythrocytes. Measurement by adenosine deaminase titration and radioisotope assays

The assay of residual adenosine deaminase (ADA) activity was used as a sensitive measure of the transport of deoxycoformycin (dCF) into human erythrocytes. Contrary to prior reports from this laboratory, the inactivation of intraerythrocytic ADA by dCF was linear rather than log-linear, with time. Linear inactivation rates were also seen when erythrocytes were preloaded with a 5-fold excess of calf intestinal ADA. The uptake of tritium-labeled dCF molecules and the rate of inactivation of ADA molecules showed an approximate 1:1 stoichiometry. The nucleoside transport inhibitors, 6-[(4-nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine (NBMPR) and dipyridamole, and the permeant, uridine, inhibited dCF transport with Ki values of 35 nM, 45 nM, and 340 microM respectively. The affinity of dCF for the nucleoside transporter was low with a Ki of approximately 10 mM for the inhibition of adenosine influx.     

The mechanism of cadmium-induced lysozyme enhancement in rabbit kidney

The effect of cadmium on the renal lysozyme level was examined by injecting male albino rabbits subcutaneously with 1 mg cadmium/kg body weight three times a week for 1 or 3 months. The lysozyme level in the renal brush border membrane of the cadmium-treated animals was elevated ten-fold. The lysozyme activity in the liver and small intestine tissue homogenates of rabbits was elevated by a 1-month treatment with cadmium, markedly elevated in the kidney, but markedly reduced in the spleen and lungs. Exposure to cadmium for 3 months produced an essentially similar effect on the enzyme level in the tissue, except for the lungs in which the lysozyme level returned to the preinjection level. This marked increase in the lysozyme level in the kidney of cadmium-treated rabbits was confirmed by an indirect immunofluorescent antibody technique. In control animals, intracellular distribution of the enzyme was selectively distributed to only a small number of proximal tubules, with none distributed in the medulla or glomerulus. However, after expose to cadmium, the renal tubules showed strongly positive lysozyme staining. In addition to an increase in intensity of the specific fluorescence, this enzyme was widely distributed not only in the proximal convoluted portion, but also in the straight portion of the proximal tubules, which essentially showed no enzyme activity under normal conditions. The enzyme in these cells was evenly distributed throughout the cytoplasm. The plasma lysozyme level increased immediately after the administration of cadmium, and detectable amounts of the enzyme began to appear in urine from the 3rd week after the first injection, with a 1-week lag after the maximum level of lysozyme in the plasma. This high level of plasma lysozyme, varied two-to fourfold over the control, and lysozymuria continued throughout the experiment. The concentration of cadmium in the renal cortex was 141 g/g wet tissue at 1 month, and 208 g at 3 months. In conclusion, the cadmium-induced enhancement of the lysozyme level in the renal cortex may be due primarily to the elevation of the lysozyme level in plasma by cadmium. The enzymatic high net positive charge, characteristic of lysozyme, may contribute greatly to this mechanism. In addition, the excretion of a large amount of lysozyme into the urine observed in a later stage may be due to the concomitant occurrence of leakage from the destroyed tubular cells and reduced tubular reabsorption of filtered enzyme, whereas lysozymuria at an early stage may be solely due to excess amounts of plasma lysozyme.Abbreviations SDS Sodium dodesyl sulfate - PAGE Polyacrylamide gel electrophoresis - IEF Isoelectric focusing - PBS 0.01 M Sodium phosphate buffer pH 7.2, 0.15 M NaCl - FITC Fluorescein isothiocyanate - AMP Adenosine 5-monophosphate - PAS Periodic acid/Schiff reagent     

Neurotoxicity of deoxycoformycin: effect of constant infusion on adenosine deaminase,adenosine, 2'-deoxyadenosine and monoamines in the mouse brain

The tight-binding adenosine deaminase inhibitor, 2'-deoxycoformycin (dCF), was continuously infused into mice by intraperitoneal implantation of microosmotic pumps delivering the compound at a rate of 0.16 mg hr^?1 kg^?1 for up to 6 days. The activity of cerebral adenosine deaminase was nearly totally inhibited. The amount of adenosine and 2'-deoxyadenosine was determined in the brain frozen in liquid nitrogen through the intact skull bone. The concentration of adenosine was about 1 $\text{nmol}\text{g}$, and was essentially not altered following treatment with deoxycoformycin. Deoxycoformycin induced a progressive increase in cerebral content of 2'-deoxyadenosine, which after 1 day of treatment equalled the amount of adenosine. The concentrations of serotonin, dopamine and noradrenaline in the brain were not altered.     

姜黄素对压力超负荷兔心肌基质金属蛋白酶表达及胶原重构的作用

目的:观察姜黄素对慢性压力超负荷兔左室肌基质金属蛋白酶 2, 9 (MMP 2,MMP 9 )表达及胶原重构的影响,并探讨其机制。方法: 36只家兔随机分为假手术组、结扎组和姜黄素组,腹主动脉次全结扎制备压力超负荷家兔模型,姜黄素组给予姜黄素(100mg·kg-1·d-1 )的聚乙二醇溶液灌胃,假手术组、结扎组给予等量的聚乙二醇。术后12wk取兔心肌行VG染色及免疫组化染色,观察胶原容积百分比 (CVF)及MMP 2,MMP 9表达情况。结果: 假手术组、结扎组、姜黄素组MMP 2的表达灰度值分别是(68±s5), (153±12), (90±7),MMP 9分别是(64±6), (148±10), (86±6);含小血管的CVF分别是 ( 8. 1±0. 9 ) %, ( 17. 7±0. 6 ) %,(13. 0±0. 8) %。慢性压力超负荷下,兔心室肌MMP 2,MMP 9表达显著增强;姜黄素显著抑制MMP 2,MMP 9的表达,并降低CVF。结论:基质金属蛋白酶(MMPs)是促使慢性压力超负荷下心肌胶原重构的重要因素,姜黄素通过抑制MMPs能够改善胶原重构。     

Activity of ectonucleotidases and adenosine deaminase in rats exposed to cigarette smoke

Cigarette smoke is a complex mixture of various toxic substances that are capable of initiating oxidative damage and promoting blood platelet alterations. In this study, we investigated the activities of the ectoenzymes NTPDase (ectonucleoside triphosphate diphosphohydrolase, CD39) and 5′-nucleotidase (CD73) in platelets as well as adenosine deaminase (ADA) in the plasma of rats exposed to aged and diluted sidestream smoke during 4 weeks. The rats were divided into two groups: I (control) and II (exposed to smoke). After the exposure period, blood was collected and the platelets and plasma were separated for enzymatic assay. The results demonstrated that NTPDase (with ATP as substrate) and 5′-nucleotidase (AMP as substrate) activities were significantly higher in group II (p?<?0.05) as compared to group I, while no significant difference was observed for NTPDase with ADP as substrate. The ADA activity was significantly reduced in group II (p?<?0.05) as compared with group I. Platelet aggregation was significantly increased in group II (p?<?0.05) as compared with group I. We suggest that these alterations in the activity of enzymes from the purinergic system are associated with an increase in platelet aggregation. However, our study has demonstrated that the organism tries to compensate for this enhanced aggregation by increasing hydrolysis of AMP and reducing hydrolysis of adenosine, a potent inhibitor of aggregation and an important modulator of vascular tone.     

姜黄素抑制TNF-α诱导的BMEC与白细胞的粘附

目的研究姜黄素(curcumin)对脑微血管内皮细胞(brain microvascular endothelium cell,BMEC)和白细胞粘附的影响。方法采用髓过氧化酶法测定经肿瘤坏死因子(tumor necrosis factor-α,TNF-α)刺激的BMEC对白细胞的粘附;以RT-PCR和Western blot方法检测在TNF-α作用下BMEC表面ICAM-1表达。结果经TNF-α刺激的BMEC明显增加其与白细胞的粘附反应;curcumin(12.5~100mg.L-1)可剂量依赖性地抑制TNF-α所诱导的BMEC与白细胞的粘附;在TNF-α刺激前30min加入curcumin可抑制BMEC的ICAM-1表达。结论curcumin对TNF-α所致的BMEC损伤具有保护作用,该作用可能是curcumin下调ICAM-1表达,抑制BMEC与白细胞的粘附,从而保护内皮细胞免受损伤。     

Differential effects of uridine adenosine tetraphosphate on purinoceptors in the rat isolated perfused kidney

BACKGROUND AND PURPOSE

Purinergic signalling plays an important role in vascular tone regulation in humans. We have identified uridine adenosine tetraphosphate (Up₄A) as a novel and highly potent endothelial-derived contracting factor. Up₄A induces strong vasoconstrictive effects in the renal vascular system mainly by P2X₁ receptor activation. However, other purinoceptors are also involved and were analysed here.

EXPERIMENTAL APPROACH

The rat isolated perfused kidney was used to characterize vasoactive actions of Up₄A.

KEY RESULTS

After desensitization of the P2X₁ receptor by α,β-methylene ATP (α,β-meATP), Up₄A showed dose-dependent P2Y₂-mediated vasoconstriction. Continuous perfusion with Up₄A evoked a biphasic vasoconstrictor effect: there was a strong and rapidly desensitizing vasoconstriction, inhibited by P2X₁ receptor desensitization. In addition, there is a long-lasting P2Y₂-mediated vasoconstriction. This vasoconstriction could be blocked by suramin, but not by PPADS or reactive blue 2. In preparations of the rat isolated perfused kidney model with an elevated vascular tone, bolus application of Up₄A showed a dose-dependent vasoconstriction that was followed by a dose-dependent vasodilation. The vasoconstriction was in part sensitive to P2X₁ receptor desensitization by α,β-meATP, and the remaining P2Y₂-mediated vasoconstriction was only inhibited by suramin. The Up₄A-induced vasodilation depended on activation of nitric oxide synthases, and was mediated by P2Y₁ and P2Y₂ receptor activation.

CONCLUSIONS AND IMPLICATIONS

Up₄A activated P2X₁ and P2Y₂ receptors to act as a vasoconstrictor, whereas endothelium-dependent vasodilation was induced by P2Y_1/2 receptor activation. Up₄A might be of relevance in the physiology and pathophysiology of vascular tone regulation.     

Cadmium retention increase: A probable key mechanism of the protective effect of zinc on cadmium-induced toxicity in the kidney

Zinc (Zn) reverses cadmium (Cd)-induced toxicity in kidneys although it increases Cd tissue burden, hence, the present study is designed to study the relationships between Cd, Zn and antioxidants in the kidneys of rats exposed to Cd orally. Male rats received either tap water, Cd or Cd + Zn in their drinking water during five weeks. Cd-induced increase in Cd and Zn accumulation was accompanied by a decrease in important variables (GSH, GSH/GSSG, CuZn SOD and GPx activities) and by an increase in others (Cd/Zn, GSSG and CuZn SOD/GPx). Zn supply intensified Cd retention and Cd/Zn; it amplified CuZn SOD activity, CuZn SOD/GPx and GSH/GSSG compared to normal values, but had no effect on Zn content increase. Besides, it ameliorated GPx activity and corrected GSSG level. High positive correlations were found between Cd concentrations and the majority of the studied variables suggesting a direct influence of Cd on them. Zn concentration had positive correlation with CuZn SOD/GPx, and negative one with GPx activity, which reflects an indirect protective effect of Zn. In conclusion, our results suggest that Zn increases Cd tissue retention in the kidney and that is probably the key mechanism of the protective effect of Zn.