The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity

Abstract

The polyphenol curcumin has several pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer features. In this study, we evaluated the effects of curcumin in cisplatin-induced nephrotoxicity in rats. Male Wistar rats were divided into four groups: (1) control; (2) cisplatin (7?mg/kg body weight, intraperitoneal as a single dose); (3) curcumin (100?mg/kg via gavage, for 10 days); and (4) cisplatin and curcumin. The cisplatin-treated rats exhibited kidney injury manifested by increased serum urea and creatinine (p?<?0.05). The kidney tissue from the cisplatin treated rats also exhibited a significant increase in the malondialdehyde (MDA) levels (p?<?0.05). The treatment with curcumin prevented a rise in the serum urea, creatinine and MDA levels when compared to the control group kidneys (p?<?0.05). The analysis the nicotinamide phosphoribosyltransferase (NAMPT) and sirtuin (SIRT) proteins (SIRT1, SIRT3 and SIRT4), which play important roles in the resistance to stress and the modulation of the threshold of cell death, showed similar trends (p?<?0.05). In the cisplatin-only treated rats, the induced renal injury decreased the levels of the NAMPT and SIRT proteins. Conversely, the curcumin increased the levels of the NAMPT and SIRT proteins in the cisplatin-treated rats (p?<?0.05). These data suggest that curcumin can potentially be used to reduce chemotherapy-induced nephrotoxicity, thereby enhancing the therapeutic window of cisplatin.     

Ameliorative potential of gemfibrozil and silymarin on experimentally induced nephrotoxicity in rats

IntroductionAcute nephrotoxicity is a frequent complication of critical illness especially in the inpatient setting. Cisplatin is one of the most active anticancer drugs. Nephrotoxicity is the most common side effect associated with cisplatin treatment. Silymarin is widely used for hepatic disorders due to its antioxidant and anti-inflammatory properties. Gemfibrozil, a hypolipidemic drug, has also antioxidant and anti-inflammatory properties.ObjectiveTo detect the effect of gemfibrozil and silymarin either alone or in combination on cisplatin-induced nephrotoxicity in rats.Subjects and methodsFifty albino rats were divided into 5 equal groups: Control untreated group, cisplatin treated group, gemfibrozil + cisplatin treated group, silymarin + cisplatin treated group, gemfibrozil + silymarin + cisplatin treated group. Blood urea, serum creatinine, creatinine clearance, urinary N-acetyl beta-d-glucosaminidase, urinary protein, tissue superoxide dismutase, malondialdehyde, reduced glutathione, tumour necrosis factor alpha and mitochondrial complex I activity were determined. Kidneys were excised for histopathological examination.ResultsGemfibrozil and/or silymarin efficiently attenuated cisplatin-induced nephrotoxicity evidenced by significant decrease in blood urea, serum creatinine, urinary N-acetyl beta-d-glucosaminidase, urinary protein, tissue malondialdehyde and tissue tumour necrosis factor alpha with significant increase in creatinine clearance, tissue reduced glutathione, tissue superoxide dismutase and mitochondrial complex I activity simultaneous with reduction of the necrotic damage and progressively increasing apoptotic index assessed by renal histopathological examination compared to the cisplatin treated group.ConclusionThe combination of gemfibrozil and silymarin has protective effects against cisplatin-induced nephrotoxicity in rats better than each of these drugs alone due to anti-inflammatory and antioxidant properties of the used drugs.     

Ifosfamide nephrotoxicity in pediatric cancer patients

The renal functions in pediatric cancer patients who received ifosfamide (IFO) treatment were evaluated and the risk factors related to IFO nephrotoxicity were determined. The medical records of all children treated with IFO were reviewed, and 62 with normal renal function before IFO treatment were selected. Nephrotoxicity was diagnosed by measuring urine β₂-microglobulin and glucose, and serum phosphate, bicarbonate, and creatinine. Forty-eight (77.4%) had a history of previous cisplatin treatment. Nephrotoxicity was detected in 20 patients (32.3%). β₂-Microglobulinuria was observed in all 20, hypophosphatemia in 10 (16.1%), hypocarbia in 2 (3.2%), glucosuria in 5 (8.1%), and decreased creatinine clearance in 7 (11.3%). The cumulative dose of IFO and a history of previous cisplatin therapy were related to nephrotoxicity. Among the 20 patients with nephrotoxicity, the median cumulative dose of IFO in patients with a low (<500 mg/m²) and high (>500 mg/m²) cumulative dose of previous cisplatin was 80 g/m² (73–102 g/m²) and 45 g/m² (11–76 g/m²), respectively. Most of the nephrotoxicity persisted after cessation of IFO treatment. In conclusion, close monitoring of IFO nephrotoxicity should be started earlier in patients with high-dose cisplatin pretreatment. Tubular proteinuria, as indicated by β₂-microglobulinuria, was the most-sensitive marker for IFO nephrotoxicity. Long-term follow-up study for reversibility of IFO nephrotoxicity is in progress. Received: 19 February 2001 / Revised: 15 May 2001 / Accepted: 18 May 2001     

Long-term nephrotoxicity of cisplatin, ifosfamide, and methotrexate in osteosarcoma

The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been investigated. The aim of the present study was to assess long-term renal function in children and adolescents who received at-risk chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg), phosphorus (P), and uric acid] were prospectively performed 5.4±2.2 (±SD) years after chemotherapy (total cumulative dose: methotrexate 41±31 g/m², ifosfamide 39±14 g/m², cisplatin 674±188 mg/m²) in 18 children and adolescents. The results were compared with 13 normal volunteers matched for age and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m² in all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05) and cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients. Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal excretion of P, Mg, and uric acid was higher in patients than in controls. Glomerular function was not significantly altered and only mild tubular dysfunction was present. Since renal excretion of P and Mg were increased in patients compared with normal volunteers and hypercalciuria was occasionally seen, divalent ion disorders are the most-likely potential complications. Received September 29, 1997; received in revised form December 12, 1997; accepted February 18, 1998     

The effects of gingko biloba extract and deferoxamine on flap viability

It has been claimed that pretreatment of tissues with a variety of agents can minimize the production of oxygen radicals and improve tissue survival after an ischemic insult. In this study, the effects of two different free radical scavengers, ginkgo biloba extract-EGb 761, and deferoxamine, were compared in a rat groin island skin flap model. The rates of skin flap necrosis were determined and biochemical enzymes including malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) levels were measured. The biopsy specimens were evaluated electron microscopically. The rates of skin flap necrosis in the treated groups were found to be lower than those in control groups (p<0.001). The biopsy specimens from radical scavenger treated groups showed that the ginkgo biloba and deferoxamine treated rat samples had significantly lower MDA; SOD, GSH-Px levels on the 2nd, 6th, 10th experiment days when compared with the results of control groups (p<0.001). However, in magnitude this marked decrease in MDA, SOD, and GSH-Px levels which was detected after 2nd, 6th and 10th days in ginkgo biloba treated group were found to be lower than in deferoxamine treated ones (p<0.05). The electron microscopic investigation also showed that the ginkgo biloba treated rat biopsy specimens had more normal tissue ultrastructures than the deferoxamine treated rat samples.     

Potential of morin and hesperidin in the prevention of cisplatin-induced nephrotoxicity

Oxidative stress is one of the important mechanisms of cisplatin-induced nephrotoxicity. Therefore, this study was designed to explore the potential protective effects of morin and/or hesperidin on oxidative stress in cisplatin-induced nephrotoxicity. This study was performed on 42 Wistar rats. Rats were divided into seven groups: control, morin, hesperidin, cisplatin, cisplatin?+?morin, cisplatin?+?hesperidin, and cisplatin?+?morin?+?hesperidin. Morin and/or hesperidin were given for 10 consecutive days by oral gavage and on the 4th day a single dose of cisplatin (7?mg/kg) was injected intraperitoneally. After administrations, on the 11th day of the experiment the animals were killed, and malondialdehyde (MDA), nitric oxide (NOx), glutathione (GSH) levels and myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD) activity were measured. Cisplatin-treated rats showed increased levels of MDA, and decreased levels of NOx also activity of CAT. Morin and/or hesperidin pretreatment prevent oxidative stress in kidney tissue, while they increase the NOx level, CAT activity, and decrease MPO activity. In conclusion, morin?+?hesperidin pretreatment may have a significant potential for protection of cisplatin-induced nephrotoxicity.     

Treatment with troxerutin protects against cisplatin-induced kidney injury in mice

Background: Cisplatin (CP) is a synthetic and anticancer drug, and one of the major side effects of CP is nephrotoxicity. This study was done to evaluate the renoprotective effects of troxerutin (Tro) in nephrotoxicity induced by CP in male mice.

Methods: In this experimental study, 28 male mice were divided randomly into four groups. Mice were treated with CP (20?mg/kg, i.p.) then Tro (75 and 150?mg/kg/day, po) was administered for three consecutive days. Blood samples were collected to determine serum creatinine (Cr) and blood urea nitrogen (BUN) levels. The kidney tissues were used for histological examination and biochemical assays. Malondialdehyde (MDA) level, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were assessed in renal tissue.

Results: Results showed a significant increase in the Cr, BUN and MDA levels and a significant decrease in the renal SOD and GPx activity by CP administration. Treatment with Tro for three consecutive days attenuated these changes. Also, the renoprotective effect of the Tro was confirmed by the histological examination of the kidneys.

Conclusions: Our results demonstrated that Tro has protective effects against CP-induced nephrotoxicity through improving the biochemical indices and the oxidative stress parameters.     

Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat

Abstract

Purpose: Clinical use of cisplatin is limited by its nephrotoxicity. Cisplatin-induced nephrotoxicity is associated with an increase in oxidative stress, leading ultimately to kidney dysfunction. The aim of this study was to investigate the effect of pomegranate seed oil against nephrotoxicity induced by cisplatin in adult rats. Methods: Animals were divided into four groups. Group I received corn oil (1?mL/kg). Group II received cisplatin (8?mg/kg). Group III and IV received pomegranate seed oil (PSO) 0.4?mL/kg and 0.8?mL/kg one hour before cisplatin injection for 3 days, respectively. Blood samples were collected by cardiac puncture and used for measuring urea and creatinine concentration. Twenty-hour urine samples were collected to measure protein and glucose concentration. The right kidney fixed in formalin for histological examination and the left kidney was homogenized for measurement of malondialdehyde and total sulfhydryl groups. Results: A significant elevation of serum creatinine, urea, urinary glucose, protein concentrations, and non-significant decrease in total thiol content and increase in MDA level in kidney homogenates were observed in cisplatin-treated rats. Also cisplatin reduced animal’s body weight. Mild-to-moderate tubular cell necrosis, hyaline casts, and vascular congestion were observed in group II. PSO pre-treatment significantly decreased urinary protein, glucose, and serum creatinine concentration. PSO also caused a decrease in serum urea, renal MDA, and increase in thiol content, but the level of these parameters were not significant. Conclusion: The present results suggest that PSO is an effective agent for the prevention of cisplatin-induced renal dysfunction and oxidative damage in rat.     

Insulin-like growth factor-I increases p21 expression and attenuates cisplatin-induced acute renal injury in rats

Background Exogenous insulin-like growth factor-I (IGF-I) promotes recovery from ischemic renal injury, but its effect on cisplatin (CDDP)-induced nephrotoxicity and its mechanisms for the attenuation of renal injury are unknown.Methods We administered recombinant human IGF-I (rhIGF-I, 150µg/day, i.p.) once a day 24h prior to and after CDDP (5mg/kg, i.v.) injection in rats.Results The rhIGF-I treatment significantly decreased serum creatinine (0.92 ± 0.11 vs 1.50 ± 0.15mg/dl; P 0.05), the tubular damage score, and the ratio of apoptotic cells to tubular epithelial cells in the outer stripe of the outer medulla on day 5 (P 0.05). rhIGF-I significantly increased the numbers of p21-positive nuclei (5.15 ± 0.19 vs 3.45 ± 0.42/×400 high-power field (HPF); P 0.05) and proliferating cell nuclear antigen (PCNA)-positive nuclei (28.61 ± 1.89 vs 18.26 ± 2.14/×400 HPF; P 0.05), but decreased the number of cyclin D1-positive cells (3.3 ± 0.3 vs 6.3 ± 1.7/×400 HPF; P 0.05) on day 3. rhIGF-I did not alter 5-bromo-3-deoxyuridine (BrdU) incorporation.Conclusions Our findings suggested that rhIGF-I increased renal p21 and PCNA expression, but reduced cyclin D1 expression in CDDP-treated kidneys. Exogenous rhIGF-I may ameliorate renal damage, in part by stopping the cell cycle at G1/S phase.     

The effect and pharmacokinetics of nafamostat mesilate adjunct to cold nondepolarizing cardioplegia in a canine model of cardiac preservation

We examined the effects of nafamostat mesilate (NM) on myocardial, biochemical, and functional changes in canine hearts. An isolated heart was preserved for 6 h at 5°C and then reperfused for 2 h at 37°C. NM was added to the cardioplegic solution. At concentrations of both 10^-7 M (n=8) and 10^-6 M (n=6), NM was able to maintain myocardial cyclic adenosine monophosphate (cAMP) at a normal level and to reduce guanosine monophosphate (cGMP) concentrations at the end of both preservation and reperfusion. The serum N-acetyl-b-D-glucosaminidase (NAG) concentration during reperfusion was lower in hearts treated with NM 10^-6 or 10^-7 M than in those without NM (P<0.05). Although NM failed to preserve myocardial concentrations of adenine nucleotide compounds, NM 10^-7 M maintained the ± dp/dt of the left ventricle after reperfusion at the same level as in the nonischemic control group and better than NM 10^-6 M or no NM (P<0.05). Myocardial uptake of NM 10^-5 M (higher concentration) was 55%±8% (6-h preservation) and 29%±15% (2-h reperfusion). We conclude that NM 10^-7 M adjunct to nondepolarizng solution does not preserve myocardial adenine nucleotide concentrations but does facilitate the recovery of left ventricular function. NM 10^-5 M (higher concentration) seems to have a high affinity for the myocardium and may depress the recovery of left ventricular function.     

甲磺酸萘莫司他中有机溶剂残留的测定

目的建立气相色谱法测定甲磺酸萘莫司他中有机溶剂残留量。方法在EC-1000（30m×0．54mm×1．2μm）毛细管柱上采用程序升温法,载气为氮气,汽化室温度200℃,检测器温度220℃,以二氧六环为内标,内标法测定甲碳酸萘莫司他中残留的甲醇、丙酮、毗啶、N,N-二甲基甲酰胺。结果在本研究色谱条件下,各溶剂及内标均能得刮良好的分离度,空白无干扰;在所考察的浓度范围内线性良好,相关系数均在0．9996以上,回收率96．7％～102．0％,检测限0．15—2．8μg／mL。结论试验建立的色谱方法简便、准确,灵敏度高,适合甲磺酸萘莫司他机溶剂残留量的检测。     

Protective effect of deferoxamine on experimental spinal cord injury in rat

Objective

To observe the protective effect of deferoxamine on experimental spinal cord injury (SCI) in rats.

Methods

Sprague-Dawley rats were randomly divided into the following four groups. Control group: rats were performed laminectomy only; SCI group: rats were performed laminectomy with SCI; DFO group: rats were injected intraperitoneally a bolus of 100 mg/kg deferoxamine after SCI; vehicle group: rats were injected intraperitoneally 0.9% saline after SCI. The SCI of animal model was made by using a modified Allen's method on T₁₀. Six rats of each group were sacrificed at 4 h after injured, and the levels of free iron and malondialdehyde (MDA) of involved spinal cord segments were measured by bleomycin assay and the thiobarbituric acid (TBA) separately. The recovery of function was assessed by Modified Tarlov's scale and inclined plane method at 7, 14, 21 d after SCI. The histologic changes of the damaged spinal cord were also examined at 7 d after SCI.

Results

Following SCI, the levels of free iron and MDA were increased significantly and the Modified Tarlov's score and inclined plane angles decreased in SCI group and vehicle group. In DFO group, the levels of free iron and MDA were not increased, but the Modified Tarlov's score and inclined plane angles decreased, the histological findings were improved as well.

Conclusion

Deferoxamine can reduce the levels of free iron and lipid peroxidation, and improve the hind limb functional status of rats with spinal cord injury.     

Effect of rosiglitazone on cisplatin-induced nephrotoxicity

Aim: Nephrotoxicity is a major side effect of cisplatin (Cis), a widely used chemotherapeutic drug. Recent studies have strongly suggested that inflammatory mechanisms may play an important role in the pathogenesis of Cis nephrotoxicity. Rosiglitazone (Ros), a peroxisome proliferator-activated receptor-gamma agonist has been recently demonstrated to regulate inflammation by modulating the production of inflammatory mediators and adhesion molecules. The aim of this study was to evaluate the effect of Ros on the prevention of Cis-induced nephrotoxicity. Methods: Eighteen male Sprague–Dawley rats weighing 150–200 g were included in the study. The rats were randomly divided into three groups: group 1: Cis-treated group; group 2: Cis–Ros-treated group; group 3: saline-treated group. Blood urea nitrogen (BUN) and serum creatinine concentrations were measured. In addition, extent of histological renal tubular injury in each animal was graded histologically. Results: Mean BUN and serum creatinine concentrations were significantly lower in group 3 than in group 1 (p < 0.05) and group 2 (p < 0.05). There were no significant differences in terms of BUN and serum creatinine concentrations between groups 1 and 2 (p > 0.05). Acute tubular injury with karyomegalic changes in corticomedullary junction was significantly higher in groups 1 and 2 than group 3 (p < 0.05). However, there were no significant differences between groups 1 and 2 (p > 0.05). Conclusion: This study indicates that post-insult administration of Ros does not seem to have a beneficial effect on prevention and severity of nephrotoxicity induced by Cis.     

Synergistic effects of nafamostat mesilate rinse and Kupffer cell blockade for rat liver preservation

Abstract  We investigated the efficacy of a new rinse solution containing nafamostat mesilate (NM) (a serine protease inhibitor) for liver preservation with modulation of Kupffer cell function. Orthotopic liver transplantation (OLT) was performed in male Lewis rats after 24 h of cold storage in University of Wisconsin organ preservation solution. After OLT, survival was determined, together with assays of blood chemistry, tissue NM metabolites, and histology 3 h after OLT. NM rinse was found to have a cytoprotective effect on liver parenchymal cells, based on enzyme data showing that NM rinse reduced the release of serum alanine aminotransferase significantly in comparison with saline rinse ( P < 0.05). However, the effect was not sufficient to improve the survival rate. In contrast, when the donor was treated with gadolinium chloride 24–30 h before graft harvest, NM rinse improved the survival rate to around 80 % compared with 25 % for saline. The assay of NM metabolites in grafted liver tissue showed that pretreatment of the donor rats with GdCl₃ delayed the degeneration of NM in the liver tissue. These data demonstrate that NM rinse and Kupffer cell blockade exert synergistic effects, leading to increased survival after cold-preserved liver transplantation.     

Reversibility of acute cyclosporin nephrotoxicity by dopamine. Micropuncture study in the rat

The ability of dopamine to neutralise the effects acutely induced by cyclosporin (CsA) on glomerular dynamics was evaluated in four groups of female Munich-Wistar rats, prepared for micropuncture: group I (n = 9), normal rats receiving saline as placebo; group II (n = 10), rats treated with CsA (20 mg/kg b.w. in 1 h); group III (n = 8) rats treated with CsA, as in group II, and then with vasodilating doses of dopamine (1.2-2.0 micrograms/100 g b.w./min in continuous intravenous infusion); group IV (n = 7), rats administered Cremophore EL, the vehicle of CsA, in corresponding doses. Single nephron GFR (SNGFR), glomerular plasma flow (GPF), afferent and efferent arteriole resistances (Ra and Re, respectively), SN filtration fraction (SNFF), ultrafiltration coefficient (Kf) were measured. Body weight, blood pressure and haematocrit were similar in the four groups. GFR was significantly reduced in group II (0.83 +/- 0.08 ml/min vs 1.29 +/- 0.01 in group I, 1.46 +/- 0.25 in group III, and 1.40 +/- 0.09 in group IV, P less than 0.05 vs all the groups), while no statistical difference was detected in urinary volume. SNGFR was significantly reduced in group II vs group I (18.7 +/- 1.8 nl/min vs 30.6 +/- 1.3, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Potentiated nephrotoxicity of cisplatin when combined with amikacin comparing young and adult rats

We compared the nephrotoxic interaction between cisplatin (CP) and amikacin (AM) in young and adult rats, using different dosage combinations. Following a single i.v. dose of CP, AM was administered s. c. for 14 days. The dose of CP was chosen to cause a 20%–50% fall in the glomerular filtration rate (GFR), while a dose of AM was chosen that had only a minimal effect on GFR. In adult rats, a decrease in GFR to 60% of the control value after CP alone was seriously aggravated by a non-toxic AM course given during 2 weeks after CP. In this combination, the GFR per 100 g body weight was reduced to 30% of control at week 2, which rose to 40% of control at week 15. In young rats, a non-toxic AM course did not aggravate the CP-induced impairment in GFR. However, when the dose of AM was increased to cause a 20% reduction in the GFR, the nephrotoxicity was potentiated. When measured at week 2, the GFR per 100 g body weight was 40% of control after the combined treatment compared with 80% of control after CP alone. As in adult rats, there was only a partial recovery of the GFR. In conclusion, in both adult and young rats, a course of AM following a single injection of CP potentiated CP-induced nephrotoxicity.     

Cisplatin nephrotoxicity in children after continuous 72-h and 3x1-h infusions

Little is known about the association be- tween the rate of cisplatin administration and the severity of cisplatin-induced renal damage in children. The purpose of this study was to compare severity and reversibility of renal damage in children after continuous and repetitive bolus administration of cisplatin and to correlate these data with pharmacokinetic parameters. Study subjects included six children (ten courses) re-ceiving cisplatin as 1-h bolus infusions on three consecutive days (3×40 mg/m²) and four children (eight courses) receiving 72-h continuous infusions (120 mg/m²). In all courses, signs of glomerular and tubular damage were seen, as evidenced by elevated urinary excretion of α₁-microglobulin, albumin and N-acetyl-β-d-glucosaminidase and decreased glomerular filtration rate (GFR). Comparing the two infusion regimens, the 1-h bolus administration of cisplatin was followed by significantly higher peak free platinum concentrations in plasma and urine (P<0.001), resulting in lower nadirs of the GFR (P<0.005). Correlations were found between both peak free platinum concentrations in plasma and urine and maxima of urinary albumin and N-acetyl-β-d-glucosaminidase excretion. Within 12 months after completion of cisplatin therapy, children in the 1-h bolus group had recovered only partially from subclinical nephrotoxicity, with five out of six showing pathological proteinuria. The results provide clear evidence that long-term ciplatin infusions are less nephrotoxic than repetitive bolus infusions. Received: 30 August 2000 / Revised: 12 February 2001 / Accepted: 14 February 2001     

去铁胺对输血相关性铁过载患者骨密度的影响

目的观察输血相关铁过载患者在使用去铁胺(DFO)降铁治疗后骨密度的变化,探讨去铁胺对铁过载骨质疏松患者辅助治疗的应用前景。方法回顾性研究22例输血相关铁过载患者临床资料,检测患者DFO降铁治疗前后的骨密度和血清生化指标。采用配对样本t检验、Wilcoxon非参数检验分析研究患者DFO降铁治疗前后骨密度以及血清生化指标的变化。结果进行DFO有效的铁螯合治疗后,患者血清铁蛋白(Fer)明显下降,由基线水平的2019.95±630.77 ng/m L降至843.61±91.01 ng/m L(P0.05);股骨颈和腰椎的骨密度明显增加,分别由基线水平的0.73±0.12 g/cm2、0.92±0.14 g/cm2增加至0.77±0.09 g/cm2、0.94±0.14 g/cm2(P0.05);骨量正常、骨量减少和骨质疏松患者分别由治疗前的4、12、6例变为治疗后的10、11、1例(P0.05)。结论 DFO降铁治疗可改善输血相关铁过载患者的低骨量状态。本研究为DFO可能用于伴有铁过载的骨质疏松症的辅助治疗提供了有意义的支撑。     

Efficacy of nafamostat mesilate as a regional anticoagulant in experimental direct hemoperfusion and in plasma exchange on humans

As an anticoagulant, we compared Nafamostat mesilate (FUT) to heparin in experimental direct hemoperfusion (DHP) and studied the efficacy of FUT in clinical plasma exchange (PE). In in vitro study, FUT (5 micrograms/ml) inhibited the activation of C4 more strongly than heparin (100 U/h), and larger dose of FUT (50 micrograms/ml) inhibited the activation of C3. Experimental DHP with FUT on jaundiced dogs was safely performed, but not with heparin. Clinical PE with FUT was safely performed and the hemostatic condition was not aggravated either during or after PE in patients with bleeding.