In vitro ex vivo assessment of Morinda citrifolia on drug metabolizing enzymes in spontaneously hypertensive rats

Morinda citrifolia Linn. (Rubiaceae), common name noni, has been used as a herbal medicine for over 2000 years. The consumption of noni, and especially the fruit, stresses the importance, urgency, and possibility of the examination of drug interaction when concomitantly administered with a drug. The objectives of this study were to determine the effects of noni juice (NJ) on aminopyrine N-demethylase (APND), uridine diphosphoglucuronosyl-transferase (UGT), and cytosolic glutathione S-transferase (GST) drug metabolizing enzymes and the molecular mechanism elucidation of NJ on APND using different inhibitors and stimulators. The in vitro results for APND showed that different concentrations of NJ significantly increased the activity in isolated hepatocytes at 1.0?ng/mL, 10?ng/mL, 10?μg/mL, 20?μg/mL, 50?μg/mL, and 100?μg/mL. The ex vivo results demonstrated that NJ (210?mg/kg) produced a statistically significant increase in APND activity following 1 day of NJ treatment. The results for UGT and GST showed a decrease in the activity of UGT at a dose of 21?mg/kg following 1 day of treatment, and at 2.1 and 21?mg/kg following 14 days of treatment. GST enzyme demonstrated an increase in activity by 100% for all doses following 1 day of treatment. Molecular mechanism elucidation of the ex vivo effect of NJ on phase I APND showed that KT5720 significantly reduced the activity as compared to control. A change in activity of APND, UGT, and GST following 1 day and 14 days of treatment suggests that all three metabolic pathways may play a role in herb–drug interaction by modulation of metabolic enzymes.     

氨基比林原料药含量测定方法的研究

氨基比林属吡唑酮类解热镇痛药,其通过选择性的抑制下丘脑前部前列腺合成酶,减少前列腺素的生物合成,使体温恢复正常,而实现疗效.目前现行法定标准是用容量分析法来测定氨基比林的含量,但该法终点无明显突跃,难以准确判断.本实验通过紫外分光光度法直接测定氨基比林原料药中氨基比林的含量,其操作简便、快速、可行,通过对两种方法的简单比较说明紫外分光光度法测得的结果准确度较高.     

偏最小二乘紫外分光光度法同时测定克感敏片中三种成分的含量

介绍了偏最小二乘法在分光光度法中同时测定复方药物的原理。用该法对克感敏片中三种成分非那西汀、氨基比林和咖啡因的含量进行了同时测定,所得平均回收率为100.2±0.4%,99.6±0.6%和100.3±0.7%(置信度为95%)。     

双波长一元线性回归分光光度法同时测定复方氨基比林注射液中三组分含量

本文依据一组含有不同比例待测和干扰组分的标准混合液的吸收值,采用一元线性回归方法,在选择最佳测定波长对的同时建立标准工作曲线方程,使其更符合实际作品测定时的情况,提高了结果的精度和可靠性,并使计算量和实验工作量得以降低。应用于复方氨基比林注射液中三组分氨基比林、安替比林和巴比妥的同时测定,其平均回收率分别为99.8%,100.4%和99.8%,变异系数分别为0.59,1.48和1.05,结果优于卡尔曼滤波法、偏最小二乘法和目标因子分析法。     

Ursodeoxycholate has no beneficial effect on liver function or histology in biliary cirrhosis in the rat

In different cholestatic conditions, the beneficial effects of the tertiary bile acid, ursodeoxycholate, have been described. It is unclear, however, whether ursodeoxycholate also affects the functional and structural alterations induced by chronic biliary obstruction. Therefore, we studied the effect of ursodeoxycholate (100 mg/kg/day) on microsomal function as assessed in vivo by the aminopyrine breath test, on portal hypertension and on the structural composition of the liver in rats with chronic (3-week) biliary obstruction. Hepatic composition was assessed stereologically. Ursodeoxycholate had no effect on any of the parameters measured. We conclude that this form of treatment does not affect advanced liver disease due to common bile duct obstruction. This finding supports one of the proposed mechanisms of action of ursodeoxycholate, namely that it interferes with the ileal absorption of more toxic endogenous bile salts.     

EGF加强大鼠胃壁细胞的泌酸活动

以氨基比林聚集为间接的泌酸指标，本实验观察了急性分离的大鼠胃粘膜壁细胞对ＥＧＦ的反应。结果表明：１．急性分离后３０分钟左右，壁细胞对较大剂量的ＥＧＦ（１００ｎＭ）的反应为胃酸分泌的减少；２．急性分离后６０分钟左右，壁细胞对ＥＧＦ（０．１－１００ｎＭ）的反应为泌酸活动的加强。结果提示壁细胞被分离后经历一功能恢复的过程，ＥＧＦ对壁细胞的生理作用可能是加强其泌酸活动。     

Antipyrine clearance,aminopyrine N-demethylase,and bilirubin udp-glucuronyl transferase activity in patients with amoebic liver abscess

Three indices of drug metabolism, antipyrine clearance in vivo, and aminopyrine N-demethylase and bilirubin UDP-glucuronyl transferase activity in liver biopsies, were studied in fifteen patients with amoebic liver abscess (with and without jaundice). The mean (± S.E.) antipyrine half-life in patients with jaundice was 21.64 (±1.52)h and in patients without jaundice was 19.36 ( ± 0.93)h. It was significantly prolonged in both groups of patients as compared to controls (11.63 ± 0.86 h). It showed a good correlation with serum albumin (p<0.01), prothrombin time index (p<0.01), and aminopyrine N-demethylase (p<0.05). Aminopyrine N-demethylase was found to be decreased in patients without jaundice but no significant change could be observed in patients with jaundice. Bilrubin UDP-glucuronyl transferase showed no significant change in either of the groups.     

Central monoamines and antinociceptive drug action

Experiments were perfomed in rats to elucidate the role of central 5-HT and catecholamines in the mediation of the antinociceptive effects of d-amphetamine, d-p-chloroamphetamine, morphine and aminopyrine. The method of Randall and Selitto (1957) was used for determining the antinociceptive effect.     

Effect of methomyl on hepatic mixed function oxidases in rats

Objective:

To study the effect of the methomyl on mixed function oxidase system in rats.

Materials and Methods:

The effect of the methomyl on mixed function oxidase was studied using different dosages, durations and sex. Microsomes were isolated using the calcium precipitation method. The levels of cytochrome P₄₅₀ , and cytochrome b₅ were determined using extinction coefficient of 91 and 85 mM^-1 respectively. The activities of drug metabolizing enzymes, hemoglobin content, liver function enzymes, and serum cholinesterase activity were assayed by using standard methods.

Results:

Intraperitoneal administration of methomyl (4 mg/kg body weight) showed significant decrease in the level of cytochrome P₄₅₀ , and the activities of aminopyrine N-demethylase and aniline hydroxylase on the third day of the treatment. Methomyl (4 mg/kg) treatment of old male rat and adult female rat also showed a decrease in the level of cytochrome P₄₅₀ , and aminopyrine N-demethylase activity. The serum samples from methomyl treated rats (male and female), when analyzed for alanine aminotransferase (SGPT) and aspartate aminotransferase (SGOT) as markers of the liver toxicity, showed significant increase in the activity. The activities of SGPT and SGOT were significantly higher in the treated rats (2 and 4 mg/kg) than in the control group. A significant decrease in the level of hemoglobin and serum cholinesterase activity was observed, when there was an increase in the dose level. A significant increase was observed in alkaline phosphatase activity at all dose levels.

Conclusion:

Methomyl influences mixed function oxidase and creates abnormality of liver functions in the rats. This effect depends on the dose and duration of methomyl.     

水溶性弱碱性药物的线性滴定

前文已谈及水溶性弱酸性药物的线性法测定。迄今为止所发表的各种文献中只涉及到用碱滴定各种弱酸性物质,对弱碱性物质的应用尚未见报道。本文对用盐酸滴定各种弱碱性药物作了尝试,获得了较好结果。