Involvement of mitochondria in acetaminophen-induced apoptosis and hepatic injury: roles of cytochrome c,Bax, Bid,and caspases

The role of apoptosis in acetaminophen (AAP)-induced hepatic injury was investigated. Six hours after AAP administration to BALB/c mice, a significant loss of hepatic mitochondrial cytochrome c was observed that was similar in extent to the loss observed after in vivo activation of CD95 by antibody treatment. AAP-induced loss of mitochondrial cytochrome c coincided with the appearance in the cytosol of a fragment corresponding to truncated Bid (tBid). At the same time, tBid became detectable in the mitochondrial fraction, and concomitantly, Bax was found translocated to mitochondria. However, AAP failed to activate the execution caspases 3 and 7 as evidenced by a lack of procaspase processing and the absence of an increase in caspase-3-like activity. In contrast, the administration of the pan-inhibitor of caspases, benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone (but not its analogue benzyloxycarbonyl-Phe-Ala-fluoromethylketone) prevented the development of liver injury by AAP and the appearance of apoptotic parenchymal cells. This correlated with the inhibition of the processing of Bid to tBid. The caspase inhibitor failed to prevent both the redistribution of Bax to the mitochondria and the loss of cytochrome c. In conclusion, apoptosis is an important causal event in the initiation of the hepatic injury inflicted by AAP. However, as suggested by the lack of activation of the main execution caspases, apoptosis is not properly executed and degenerates into necrosis.     

中成药中对乙酰氨基酚含量测定的4种方法及比较

目的：运用4种含量测定方法测定中成药中对乙酰氨基酚的含量,并比较其精确度、回收率和适应性。方法：采用滴定法、双波长分光光度法、紫外吸收系数法及高效液相色谱法。结果：四种方法所测的含量有所不同。结论：用高效液相色谱法测定中成药中对乙酰氨基酚的含量,方法简便、准确、专属性强。     

Substances used in deliberate self-poisoning 1985-1997: trends and associations with age, gender, repetition and suicide intent

Background: Rates of deliberate self-poisoning have increased in recent years. While over-the-counter availability and prescribing patterns may influence trends in substances used in overdose, these may also be related to clinical characteristics of patients. We investigate trends in substances used for self-poisoning and the influence of age, gender, suicidal intent and repetition status on the substances used. Method: Data collected by the Oxford Monitoring System for Attempted Suicide were used to review trends and patterns of self-poisoning between 1985 and 1997. Results: There were substantial increases in self-poisoning with paracetamol and antidepressants. While the increase in antidepressant self-poisoning closely paralleled local prescribing figures during 1995–97, SSRI antidepressant overdoses occurred somewhat more often than expected compared with tricyclic overdoses. Paracetamol overdoses were more common in first-timers and young people, whereas overdoses of antidepressants and tranquillizers were more common in repeaters and older people. Self-poisoning with gas and non-ingestible poisons was associated with high suicidal intent. Conclusions: There have been marked changes in the substances used for self-poisoning, which seem primarily to reflect availability, as do the influences of age and repeater status on choice of substances used. Degree of suicidal intent may also influence choice of method of self-poisoning. Accepted: 31 January 2001     

HPLC-ELSD-UV法同时测定氨酚那敏三味浸膏胶囊中长梗冬青苷、白花前胡甲素、白花前胡乙素

目的 建立氨酚那敏三味浸膏胶囊中长梗冬青苷、白花前胡甲素和白花前胡乙素的定量分析方法.方法 采用HPLC-ELSD-UV法测定长梗冬青苷、白花前胡甲素和白花前胡乙素,色谱柱为Venusil XBP-C18 (4.6 mm× 250 mm,5 μm),流动相为乙腈-水,梯度洗脱,体积流量为1.0 mL/min,紫外检测波长为320 nm;ELSD参数:漂移管温度为80℃,氮气体积流量为2.5 mL/min,雾化温度为36 ℃,柱温30℃.结果 长梗冬青苷在1.071 6～5.358 μg范围内的线性关系良好(r =0.999 1),平均回收率100.3％,RSD为2.05％(n=9);白花前胡甲素和白花前胡乙素分别在0.892 4～4.462 μg(r =0.999 9)和0.486 8～2.434 μg(r =0.999 7)范围内线性关系良好,平均回收率分别为100.03％、99.02％,RSD为2.01％、1.98％(n=9).结论 本方法测定结果准确可靠,重复性好,可为氨酚那敏三味浸膏胶囊的质量控制提供定量评价方法.     

HPLC法测定小儿氨酚黄那敏片中对乙酰氨基酚和马来酸氯苯那敏的含量

目的：建立HPLC法同时测定小儿氨酚黄那敏片中对乙酰氨基酚和马来酸氯苯那敏含量。方法：采用HypersilC18（150mm×4．6mm,5μm）色谱柱,甲醇-0．05mol·L^-1磷酸二氢钾溶液-三乙胺（10：90：0．02）（用磷酸调pH=3．4）为流动相,检测波长为216nm,柱温为30℃,流速为1．0ml·min^-1,进样量为20μl。结果：对乙酰氨基酚、马来酸氯苯那敏分别在40．08-240．48μg·ml^-1（r=0．9992）和0．37～2．21μg·ml^-1（r=0．9971）浓度范围内呈现出良好的线性关系;方法平均回收率分别为99．75％和98．95％;RSD分别为0．23％和0．36％。结论：该方法简便、快速,两组分分离度好,其他成分无干扰,测定结果准确可靠,可作为该制剂质量控制的有效方法。     

含对乙酰氨基酚的感冒药及柴芩清宁胶囊对脂多糖和干酵母大鼠发热模型的解热作用研究

目的 研究含对乙酰氨基酚的西药对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片及中成药柴芩清宁胶囊对脂多糖（LPS）及干酵母大鼠发热模型的解热作用。方法 制备大鼠100 μg/kg LPS及20%干酵母发热模型;乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片高、中、低剂量分别为205.67、102.83、51.42 mg/kg,以对乙酰氨基酚计;柴芩清宁胶囊高、中、低剂量分别为1110.60、555.30、277.65 mg/kg,以胶囊内容物质量表示,ig给药。观察大鼠体温变化,计算平均最大体温上升高度（△T）及体温反应指数（TRI）,绘制平均升温曲线。结果 对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片及柴芩清宁胶囊各剂量组对LPS及干酵母大鼠发热模型均具有显著解热作用,且均存在一定剂量效应关系。结论 对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片及柴芩清宁胶囊对LPS及干酵母大鼠发热模型均有一定解热作用,3种西药的解热作用起效快但是作用时间短,而柴芩清宁胶囊表现为起效慢但是作用时间长。     

氮酮对扑热息痛渗透裸鼠皮肤的促透作用

以裸鼠皮肤为隔膜的上下扩散的２个简单扩散小室研究氮酮对扑息痛透皮渗透促进作用。     

Acute effects of vitamin B6 and fixed combinations of vitamin B1, B6, B12 on nociceptive activity evoked in the rat thalamus: Dose-response relationship and combinations with morphine and paracetamol

Summary Nociceptive activity was elicited in neurones of the thalamus by supramaximal electrical stimulation of afferent C fibres in the sural nerve of rats under urethane anesthesia. The fixed combination of vitamin B₁, B₆, B₁₂ (Neurobion^®) as well as of vitamin B₆ administered by i.p. injection dose-dependently reduced the evoked nociceptive activity. The ED₅₀ of Neurobion^® is 4.6 ml/kg (at 100 min after injection) and that of vitamin B₆ is 189mg/kg (at 90 min after injection). The minimum effective doses of Neurobion^® and vitamin B₆ are 0.5 ml/kg and 40 mg/kg, respectively. When Neurobion^® or vitamin B₆ were given at their minimum effective doses, and the minimum effective doses of morphine (0.025 mg/kg) or paracetamol (5 mg/kg) were injected i.v. 80 min later, i.e., when the maximum effect of higher doses of Neurobion^® or vitamin B₆was about to develop, no supraadditive effect developed. It is concluded that the antinociceptive effect caused by a single injection of Neurobion^® is largely due to vitamin B₆. Vitamin B₁₂ may contribute to this effect, whereas vitamin B₁ alone exhibited only a slight effect on nociception. Moreover, it appears that Neurobion^® produces its antinociceptive effect after a single injection and after repeated administration during several days by different mechanisms so that the effect of analgesic agents is not enhanced following a single injection of Neurobion^® but may be enhanced after repeated administration of the compound.     

Hepatoprotective studies on Sida acuta Burm. f.

Ethnopharmacological relevance

Sida acuta Burm. f. (Malvaceae) is used in Indian traditional medicine to treat liver disorders and is useful in treating nervous and urinary diseases and also disorders of the blood and bile.

Aim of the study

Evaluation of the hepatoprotective properties of the methanolic extract of the root of Sida acuta (SA) and the phytochemical analysis of SA.

Materials and methods

The model of paracetamol-induced hepatotoxicity in Wistar rats, liver histopathological observations, hexobarbitone-induced narcosis and in vitro anti-lipid peroxidation studies were employed to assess the hepatoprotective efficacy of SA. Phytochemical assay of SA was conducted following standard protocols.

Results

Significant hepatoprotective effects were obtained against liver damage induced by paracetamol overdose as evident from decreased serum levels of glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, alkaline phosphatase and bilirubin in the SA treated groups (50, 100, 200 mg/kg) compared to the intoxicated controls. The hepatoprotective effect was further verified by histopathology of the liver. Pretreatment with Sida acuta extract significantly shortened the duration of hexobarbitone-induced narcosis in mice indicating its hepatoprotective potential. Phytochemical studies confirmed the presence of the phenolic compound, ferulic acid in the root of Sida acuta, which accounts for the significant hepatoprotective effects observed in the present study.

Conclusion

The present study thus provides a scientific rationale for the traditional use of this plant in the management of liver disorders.