美洛昔康对大鼠致畸敏感期的毒性试验研究

美洛昔康在受孕大鼠致畸敏感期(受孕后第6～15天)给药,剂量分别为7.0,3.5,1.8 mg/kg.结果未发现美洛昔康对胎鼠有致畸作用,但该药可使胎鼠体重减轻,吸收胎和死胎增多,骨骼发育迟缓,尤以给予高剂量美洛昔康时明显.     

拓扑替康对大鼠的胚胎毒性及致畸性研究

目的:观察拓扑替康对大鼠的致畸作用和胚胎毒性.方法:在受孕大鼠致畸敏感期(受孕后第6～15 d),拓扑替康静脉给药,剂量分别为0.200,0.067,0.022 mg/kg.结果:拓扑替康使受孕母鼠和胎鼠体重减轻,吸收胎数增多,胎鼠骨骼发育迟缓,高中剂量组中胎鼠骨骼及内脏均有畸形发生.结论:拓扑替康有较强的致畸作用和胚胎毒性作用.     

新型选择性环氧合酶-2抑制剂的研究及临床应用

目的:对新型选择性环氧合酶-2抑制剂的研究及临床应用进行谈论分析。方法:将100只大鼠根据体重分为溶剂对照组、美洛昔康高剂量组、美洛昔康中剂量组、美洛昔康低剂量组及吡罗昔康对照组,对美洛昔康抗炎镇痛的效果进行讨论分析。结果:美洛昔康低剂量组、美洛昔康中剂量组、美洛昔康高剂量组、吡罗昔康对照组和溶液对照组在给药后1.5小时、3小时及6小时痛阀有明显的升高,数据差异具有统计学意义(P0.05)。结论:美洛昔康具有很好的抗炎镇痛效果。     

熊果酸和环氧化酶-2抑制剂对胃癌细胞增殖的影响

目的 探讨熊果酸和美洛昔康对人胃癌细胞株SGC-7901增殖的调控作用.方法 SGC-7901细胞接种于含10%胎牛血清的RPMI-1640培养液中,常规培养24 h后加熊果酸或美洛昔康,约物终浓度均为10、20、40、80μmol/L,分别培养12、24和48 h,四甲基偶氮唑盐(MTT)比色分析细胞增殖,Western blot检测环氧化酶-2(COX-2)表达.结果 熊果酸和美洛昔康两者均剂量和时间依赖性地抑制SGC-7901细胞增殖,熊果酸的抑制作用小于美洛昔康(P＜0.05).熊果酸和美洛昔康剂量依赖性地抑制SGC-7901细胞COX-2表达,熊果酸抑制COX-2表达的作用小于美洛昔康(P＜0.05).结论 熊果酸和美洛昔康均抑制胃癌细胞增殖;其机制可能与COX-2表达下调有关.     

玻璃酸钠联合美洛昔康治疗类风湿性关节炎

目的观察玻璃酸钠(SH)联合美洛昔康治疗类风湿关节炎的疗效。方法将120例类风湿性关节炎患者随机分为SH组、美洛昔康组、SH+美洛昔康联合用药组,每组40例。SH组仅关节腔内注射SH;美洛昔康组仅服用美洛昔康;联合用药组关节腔内注射SH,并服用美洛昔康。美洛昔康口服7.5 mg/次,2次/d;SH关节腔内注入,2 mL/次,1次/周。对治疗前及治疗5周后结果进行比较。结果经5周治疗后,3组患者的临床指标和血沉均显著改善(P<0.05)。联合用药组的临床指标及血沉、CRP改善值均优于SH组和美洛昔康组(P<0.05)。联合用药组的疗效较SH组及美洛昔康组有显著性差异(P<0.05)。结论 SH联合美洛昔康治疗类风湿关节炎疗效明显优于单用美洛昔康和单用SH,且安全性较好。     

美洛昔康栓剂治疗强直性脊柱炎62例

目的:评价美洛昔康栓剂治疗强直性脊柱炎(AS)患者的疗效和安全性。方法:126例AS患者,随机分为治疗组62例和对照组64例,分别应用美洛昔康栓和美洛昔康片,剂量均为15mg·d~(-1),疗程6周。结果:治疗组与对照组的总有效率分别为84.49％和77.42％,2组比较差异无显著性(P>0.05),2组总计不良事件发生率分别为12.90％和21.87％,不良事件主要集中在胃肠道,无严重不良事件发生。结论:美洛昔康栓对AS患者的止痛效果及安全性与美洛昔康片类似,且总计不良事件发生率和单项最高不良事件发生率均低于片剂组。     

美洛昔康口腔崩解片人体药动学及生物等效性评价

目的评价美洛昔康口腔崩解片的生物等效性。方法22名健康男性志愿者,随机交叉单剂量口服美洛昔康口腔崩解片或美洛昔康片7.5mg后,采用高效液相色谱法测定血药浓度。结果美洛昔康口腔崩解片与美洛昔康片的Cmax分别为(1501.14±323.76)、(1563.74±417.94)ng/ml,tmax分别为(4.77±2.20)、(4.96±2.24)h,t1/2分别为(24.28±6.59)、(24.76±7.35)h,AUC0~t分别为(49179.57±12214.63)、(51414.97±14419.56)(ng.h)/ml;美洛昔康口腔崩解片的相对生物利用度为(98.09±18.03)%。结论美洛昔康口腔崩解片与美洛昔康片的主要药动学参数均无显著性差异,二者具有生物等效性。     

美洛昔康片剂溶出度的考察

对美洛昔康片剂的溶出条件和方法进行了考察,并用分光光度法测定了美洛昔康片剂的溶出度,结果表明本法简便,准确性高,美洛昔康片剂溶出性能良好。     

美洛昔康抗炎作用的实验研究

目的观察美洛昔康的抗炎作用。方法采用大鼠急性、亚急性及免疫性炎症模型,观察美洛昔康对角叉菜胶致大鼠足跖肿胀和大鼠棉球肉芽肿的影响以及美洛昔康对大鼠佐剂性关节炎的预防和治疗作用。结果美洛昔康对多种致炎剂引起的炎性水肿均具有明显的抑制作用,1.0和3.0mg     

国产美洛昔康片相对生物利用度研究

目的24名健康男性志愿受试者随机交叉单剂量口服国产美洛昔康片和进口美洛昔康片15mg,研究国产片剂的人体相对生物利用度。方法采用高效液相色谱法测定血浆中美洛昔康的浓度,并进行药代动力学研究及两制剂生物等效性评价。结果对所测得的血药浓度-时间数据用3P97进行拟合,受试者的药-时曲线符合二室模型。国产美洛昔康片与莫比可的Cmax分别为1.34±0.35mg     

Evaluation of the concomitant use of methotrexate and curcumin on Freund's complete adjuvant-induced arthritis and hematological indices in rats

Objective:

To evaluate the concomitant administration of methotrexate and curcumin for antiarthiritic activity in rats.

Materials and Methods:

Arthritis was induced in rats following a single subplantar injection of Freund''s complete adjuvant (0.1 ml). Rats were divided into six groups of six animals each. Group I and II were control injected with saline and Freund''s complete adjuvant (0.1 ml), respectively. Group III arthritic rats were treated with curcumin (100 mg/kg, i.p.) on alternate days. Group IV received methotrexate (MTX) (2 mg/kg, i.p.) once in a week. Group-V and VI were treated with MTX (1 mg/kg, i.p.) once in a week and after 30 min received curcumin (30 mg/kg and 100 mg/kg, thrice a week, i.p.) from 10^th to 45^th days, respectively. Body weight and the paw volume was measured on 9^th, 16^th, 23^rd, 30^th, 37^th, and 45^th days. Determination of complete blood cell counts, hemoglobin concentration, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin concentration was determined on the 46^th day.

Results:

An improvement in body weight and a significant (P < 0.05) reduction in arthritis was observed with the combination treatment as compared to the positive control. A significant improvement in the hematological profile was also observed in rats treated with curcumin and methotrexate.

Conclusion:

The study showed a significant anti-arthritic action and protection from hematological toxicity with the combination treatment of methotrexate and curcumin.     

Evaluation of developmental toxicity of guaifenesin using pregnant female rats

Objectives:Guaifenesin possesses expectorant, muscle relaxant, and anticonvulsive properties. To the best of our knowledge, the promising data regarding the developmental toxicity of guaifenesin are scarce. The current study investigates the developmental toxic effects of guaifenesin in detail using female rats.Results:A significant reduction in maternal weight, and food/water intake, was observed, however, no mortality and morbidity were observed. About 14 dead fetuses were found in Group-3 and -4 each, while 26 in Group 5. Morphological analysis revealed 21.2%, 45.4%, 67.2%, and 86.9% of total fetuses having hemorrhagic spots in Group-2, -3, -4, and -5, respectively. Dropping wrist/ankle and kinky tail were found in Group-4 and -5 only. Morphometric analysis showed a significant decline in fetal weight, full body length, skull length, forelimb length, hindlimb length, and tail length in all guaifenesin treated groups. Skeletal examination displayed that only Group 5 fetuses had increased intercostal space between 7^th and 8^th rib. We also observed improper development of carpals, metacarpals, tarsals, and metatarsals of the Group 5 fetuses.Conclusion:Guaifenesin showed a significant developmental toxicity at selected test doses; therefore, a careful use is suggested during pregnancy.KEY WORDS: Developmental toxicity, embryotoxicity, fetotoxicity, guaifenesin, teratogen, toxicology     

The Late and Persistent Pathogenic Effects of Cadmium at Very Low Levels on the Kidney of Rats

Cadmium (Cd) is an important nephrotoxic pollutant. To examine late effects on the kidney of individuals previously exposed to chronic Cd at very low levels, male Wistar rats were given 20 nmol/kg i.p. injections of Cd every other day for 4 weeks. At the 20^th, 28^th, 36^th, 44^th and 52^nd week of the study, renal metal accumulation, morphology and function were examined. Immunochemical staining was performed to detect renal 3-nitrotyrosine (3-NT) accumulation, metallothionein (MT) expression, cell proliferation and global DNA methylation. Results showed that renal Cd concentration and MT expression along with 3-NT accumulation were significantly higher in the Cd group than that in the control. Histopathologically renal tubule damage at the early stage and hyperplasia at the late stage were observed in the Cd group. Renal fibrosis in glomeruli was evident in the Cd group, particularly at the late stage of the study. Immunoreactivity of global DNA methylation was markedly diminished in the Cd group at both 20^th and 52^nd weeks. These results suggest that previous exposure to chronic Cd at very low level induced persistent damaging effects on the kidney along with increases in cell proliferation and global DNA hypomethylation.     

The effect of sodium valproate on the biochemical parameters of reproductive function in male albino Wistar rats

Objective:

To assess the effects of sodium valproate on intratesticular testosterone and lactic dehydrogenase level in rats.

Methods:

Male Wistar rats (12 weeks old) were treated with sodium valproate and sacrificed at the end of the 2^nd, 4^th, 5^th, 7^th, 10^th and 15^th week, after the last exposure to sodium valproate. The testes were removed, weighed and processed for biochemical analysis.

Results:

The intratesticular testosterone level was significantly (P<0.001) reduced in 200 mg/kg and 400 mg/kg treated rats. The intratesticular lactate dehydrogenase (LDH) level was significantly (P<0.001) increased by valproate in a time dependent manner.

Conclusion:

Valproate causes reversible change in intratesticular testosterone and LDH level.     

Cardioprotective effect of fenugreek on isoproterenol-induced myocardial infarction in rats

Objectives:

This study is designed to evaluate the cardioprotective effect of fenugreek on isoproterenol- induced myocardial infarction and is investigated by an in vivo method in rats.

Materials and Methods:

Male Wistar albino rats were divided into four groups (n=10). Group I received 0.5% CMC treated as normal control group. Group II received isoproterenol (85 mg/kg body weight) intraperitoneal (i.p.) for two consecutive days (14^th and 15^th days). Group III received fenugreek (250 mg/kg body weight) intragastric intubation for 15 days. Group IV rats received fenugreek as in Group III and additionally isoproterenol was given for two consecutive days (14^th and 15^th days).

Results:

The results described the cardioprotective effect that observed in Group IV showed significantly (P< 0.05) decreased levels of TBARS and enhanced the activities of both enzymatic and non-enzymatic antioxidants (SOD, CAT, GPx and GSH) in myocardial infarcted rats when compared to Groups II and III. Histopathological studies were also co-relating with the above biochemical parameters.

Conclusion:

These findings concluded the cardioprotective effect of fenugreek on lipid peroxidation and antioxidant defense system during isoproterenol-induced myocardial infarction in rats.     

Antiovulatory and abortifacient effects of Areca catechu (betel nut) in female rats

Objectives:

To study the antiovulatory and abortifacient effects of ethanolic extract of Areca catechu in female rats.

Materials and Methods:

For antiovulatory effect, ethanolic extract of A. catechu at 100 and 300 mg/kg doses was administered orally for 15 days. Vaginal smears were examined daily microscopically for estrus cycle. Rats were sacrificed on 16^th day. Ovarian weight, cholesterol estimation, and histopathological studies were done. Abortifacient activity was studied in rats at 100 and 300 mg/kg doses administered orally from 6^th to 15^th day of pregnancy. Rats were laparotomised on 19^th day. The number of implantation sites and live fetuses were observed in both horns of the uterus.

Results:

The extract of A. catechu showed a significant decrease in the duration of estrus at 100 mg/kg (P = 0.015) and 300 mg/kg doses (P = 0.002) as compared with control. Metestrus phase was also significantly reduced at 100 mg/kg (P = 0.024) and 300 mg/kg doses (P = 0.002). There was a significant increase in proestrus (P < 0.001) phase. However, diestrus phase was unchanged. Histopathological study of the ovaries showed mainly primordial, primary, and secondary follicles in the test groups as compared to control. There was also a significant (P = 0.002) decrease in ovarian weight and a significant (P = 0.021) increase in ovarian cholesterol level at 100 mg/kg dose. In the study to evaluate abortifacient effect, the mean percentage of abortion with 100 and 300 mg/kg doses were 75.5% and 72.22%, respectively, which was significantly (P = 0.008 and P = 0.006, respectively) increased when compared with control.

Conclusion:

The ethanolic extract of A. catechu at doses of 100 and 300 mg/kg has antiovulatory and abortifacient effects.     

Cardioprotective effect of ammonium glycyrrhizinate against doxorubicin-induced cardiomyopathy in experimental animals

Objective:

The objective of this study was to evaluate the cardioprotective effect of herbal bioactive compound ammonium glycyrrhizinate against doxorubicin-induced cardiomyopathy, in experimental animals.

Materials and Methods:

Ammonium glycyrrhizinate (50, 100, 200 mg/kg, p.o.) was administered for four weeks in albino rats. Cardiomyopathy was induced with a dose of 2.5 mg/kg i.p. of doxorubicin on 1^th, 7^th, 14^th, 21^th, 28^th day in the experimental animals. At the end of the experiment, on 29^th day, serum and heart tissues were collected and hemodynamic, biochemical and histopathological studies were carried out.

Results:

Administration of doxorubicin in normal rats showed significant (P < 0.001) changes in body weight, feed intake, urine output, hemodynamic parameters like (blood pressure, heart rate, cardiac output) and in lipid profile (cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, very low density lipoprotein) indicating cardiomyopathy symptoms. Animals treated with ammonium glycyrrhizinate significantly (P < 0.05) decreased triglyceride, cholesterol, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels. Moreover, high density lipoprotein (HDL) levels increased in rats treated with ammonium glycyrrhizinate as compared with the normal group.

Conclusion:

Ammonium glycyrrhizinate is effective in controlling serum lipid profile and cardiac complications in experimentally induced cardiomyopathy in animals.KEY WORDS: Ammonium glycyrrhizinate, cardiac failure, cardiomyopathy, doxorubicin     

Die renale Säure- und Ammonium-Ionen-Ausscheidung normaler und adrenalektomierter Ratten und ihre Beeinflussung durch Nebennierenrindenhormone

Summary The renal excretion of acid and ammonium ions after an oral load of monosodium-phosphate (1.2 mEq. per rat) was studied in groups of adrenalectomized er sham-operated rats, maintained on 0.9 per cent NaCI solution and water, on the 6^th or 12^th day after operation. Untreated groups were compared to groups receiving either Corticotropin (25 U./kg./day s.c.) or Cortisone acetate (12.5 mg./kg./day s.c.) er (7.5 mg./kg./day s.c.) or D,L-Aldosterone acetate Cortexone acetate (0.15 mg./kg./day s.c.) from the 3^rd to the 12^th day after opetarion.In sham-operated rats Cortisone increased H⁺ excretion and diuresis on the 6^th day after operation (3^rd day of treatment). This influence did not persist on the 12^th day. Ammonium excretion also was enhanced by Cortisone and Aldosterone on the 6^th day only, by Cortexone on the 6^th and 12^th day after operation.In adrenalectomized salt-maintained rats the renal excretion of H⁺ as weil of NH₄ ⁺ ions after a phosphate load, was considerably depressed. The titratable acidity of the urine, though, was still higher than in adrenalectomized animals not given phosphate. The depression of H⁺ and ₄ ⁺ excretion was counteracted by treatment with Cortisone and Cortexone, both hormones being more active on the 3^rd than on the 9^th day of treatment. Corticotropin or Aldosterone did not improve acid or ammonium excretion.It was concluded that suppression of adrenocortical secretion interferes with the renal tubular secretion of H^th and of NH₄ ⁺ ions. While H⁺ secretion, though depressed, can still be raised by an acid load the excretion of NH₄ ⁺ ions falls under the basic level. Disturbed renal ammonium excretion may, therefore, contribute to the development of metabolic acidosis in adrenalectomized salt-maintained rats .

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Mit 2 Textabbildungen

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Distribution,metabolism, and excretion of musk xylene in rats

Distribution, metabolism and excretion of musk xylene (MX) were investigated in male Wistar rats. Urinary and fecal excretion accounted for 10 and 75% of the dose (70 mg/kg), respectively, on day 7 after orally administration of³H-MX to rats. Total residue of radioactivity in tissues on day 7 was less than 2.0% of the administered dose. The highest concentration was found in adipose tissue and the second was in liver. Some metabolites of MX were identified using GC-MS and NMR after purification by column or thin layer chromatography of feces, bile and urine extracts. MX, 2-NH₂-MX, 2-Ac-MX, 2-NH₂-3-CH₂OH-MX, and 2-NH₂-5-tert-BuOH-MX were found in feces, bile and urine. 4-NH₂-MX and metabolite X were found in feces and urine. 4-NH₂-3-CH₂OH-MX was found in urine. HO-MX was found in bile. The major route of excretion for MX was the feces via bile. The reduction of the 2-nitro group of MX to the amino group was a key step in metabolism. Further metabolism of 2-NH₂-MX may proceed by decreased steric hindrance of functional group.