异甘草酸镁与硫普罗宁在乳腺癌术后化疗过程中保肝作用的比较

目的探讨异甘草酸镁与硫普罗宁二种保肝药物对治疗乳腺癌化疗所致肝损伤的保护作用。方法选取2010年6月—2013年6月经病理学诊断为乳腺癌的女性患者共60例,随机分为二组,每组30例。分别使用异甘草酸镁与硫普罗宁对二组患者进行治疗,为期1周。统计患者肝脏酶学水平变化及不良反应发生率并进行比较。二组患者在治疗前年龄、体重、肝功能等方面差异无统计学意义(P>0.05)。结果二组患者经药物治疗后,血清谷丙转氨酶(Alanine aminotransferase,ALT)及谷草转氨酶(Aspartate aminotransferase,AST)水平均下降,差异具有统计学意义(P<0.05);在二组患者肝损伤程度相一致的情况下,经药物治疗后,异甘草酸镁组患者血清ALT、AST水平及出现不良反应患者数(3.3%)明显低于硫普罗宁组(30.0%),差异有统计学意义(P<0.05)。结论异甘草酸镁及硫普罗宁均有保肝作用,但异甘草酸镁降低血清肝酶的效果明显优于硫普罗宁,且不良反应较少,应在临床上广泛推广。     

肝复康颗粒保肝作用的实验研究

探讨肝复康颖粒的保肝作用。方法：评价肝复康对,D-半乳糖胺、硫化乙酰胺致大鼠急性肝损伤、四氯化碳致小鼠急性肝损伤的作用,并与联苯双醋作对照。结果：肝复康能明显抑制D-半乳糖胺和硫化乙酰胺、四氯化碳致急性肝损伤动物的SGPT、SGOT值的升高（P〈0．05）。结论：肝复康具有一定的保肝作用。     

Pharmacological evaluation of Ipomoea asarifolia (Desr.) against carbon tetrachloride-induced hepatotoxicity in rats

Ethnopharmacological relevance

Ipomoeaasarifolia (Desr.) Roem. and Schult. is used traditionally in some parts of Africa for the treatment of a variety of diseases. This study attempts to validate its hepatoprotective activity by evaluating the prophylactic and curative properties of the methanolic extract of Ipomoea asarifolia (IA) leaves.

Materials and Methods

Liver damage was induced by administering 0.5 ml/kg of an equal mixture of carbon tetrachloride (CCl₄) in olive oil intraperitoneally on alternate days, for 5 days and the plant extract was given orally daily, for 7 days at doses of 100, 200 and 400 mg/kg.

Results

Pre-treatment with the extract significantly (P<0.05) decreased CCl₄-induced elevation in serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, triglycerides, bilirubin and cholesterol, better than the standard drug silymarin at 100 mg/kg. In the curative study, IA significantly (P<0.05) reversed CCl₄-induced liver damage, comparable to silymarin. Hepatoprotective potential was further supported by decrease in pentobarbitone sleeping time and improved hepatic tissue histopathology.

Conclusion

These results indicate that I. asarifolia leaves have potent hepatoprotective activity against CCl₄-induced hepatic damage in rats.     

Effects of four Indian medicinal herbs on Isoniazid-, Rifampicin- and Pyrazinamide-induced hepatic injury and immunosuppression in guinea pigs

AIM: To evaluate and compare the hepatoprotective and immunomodulatory effects of Curcuma longa (CL), Ocimum sanctum (OS), Tinospora cordifolia (TC) and Zizyphus mauritiana (ZM) on liver injury and immunosuppression induced by Isoniazid (INH), Rifampicin (RIF) and Pyrazinamide (PZA). METHODS: Duncan Hartley guinea pigs, weighing 700-1050 g, were treated orally with 50 mg/kg of INH, 100 mg/kg of RIF and 300 mg/Kg of PZA for 21-d. 200 mg/kg (bw) of each herb crude extract was administered to the herb control group and 2-h previous to INH + RIF + PZA (AKT) doses to the Herb + AKT groups. Serum alanine aminotransferase (ALT), aspertate aminotransferase (AST) bilirubin and Alkaline Phosphatase (ALP) were assessed on d 0 and 21 in all the groups. Phagocytic % (P%), Phagocytic Index (PI) and Chemotactic Index (CI) were also measured as immunologic parameters. Histological analysis was carried out to assess injury to the liver. RESULTS: The AKT treated control group showed hepatotoxicity as judged by elevated serum AST 5-fold, AST/ALT ratio 4-fold, ALP 2-fold and hepatological changes, such as focal necrosis, portal triaditis and steatosis. Immune function was suppressed as judged by decreased P% (51.67 ?1.68 vs 40.61 ?1.28, P < 0.01), PI (2.0725±0.05 vs 0.61±0.05, P < 0.001) and CI (1.8525±0.04 vs 0.695±0.07, P < 0.001). All four herb treated groups showed normal liver histology, enzyme levels and increased P%, while PI and CI were enhanced in the TC and ZM treated groups, respectively. CL + AKT, TC + AKT and ZM + AKT showed nearly normal histology with minimal inflammation and microvesicular steatosis, while OS + AKT showed partial protection. Hepatotoxicity was prevented by restricting the rise of AST by 2-fold in CL + AKT and TC + AKT groups and by 3-fold in OS + AKT and ZM + AKT groups, AST/ALT by 2-fold and ALP to normal levels in all four groups. All four herb + AKT groups showed normal to enhanced neutrophil function. CONCLUSION: All four herbs showed hepatoprotective potential and prevented immunosuppression. CL and TC showed the highest hepatoprotective activity, while TC and ZM showed strong immunostimulatory activity.     

Hepatoprotective effect of manual acupuncture at acupoint GB34 against CCl4-induced chronic liver damage in rats

AIM: To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan (GB34) on CCl4-induced chronic liver damage in rats. METHODS: Rats were injected intraperitoneally with CC4l (1 mL/kg) and treated with manual acupuncture using reinforcing manipulation techniques at left GB34 (Yanglingquan) 3 times a week for 10 wk. A non-acupoint in left gluteal area was selected as a sham point. To estimate the hepatoprotective effect of manual acupuncture at GB34, measurement of liver index, biochemical assays including serum ALT, AST, ALP and total cholesterol, histological analysis and blood cell counts were conducted. RESULTS: Manual acupuncture at GB34 reduced the liver index, serum ALT, AST, ALP and total cholesterol levels as compared with the control group and the sham acupuncture group. It also increased and normalized the populations of WBC and lymphocytes. CONCLUSION: Manual acupuncture with reinforcing manipulation techniques at left GB34 reduces liver toxicity, protects liver function and liver tissue, and normalizes immune activity in CCl4-intoxicated rats.     

Protective Activity of the Stem Bark Aqueous Extract of Musanga Cecropioides in Carbon Tetrachloride- and Acetaminophen-induced Acute Hepatotoxicity in Rats

The hepatoprotective activities and the mechanisms of actions of Musanga cecropioides stem bark aqueous extract (MCW) were investigated on acute hepatocellular injuries induced by intraperitoneal (IP) carbon tetrachloride (CCl₄) (20% CCl₄/olive oil, 1.5 mL/kg) and 800 mg/kg/IP of acetaminophen (APAP) in normal saline, in male Wistar rats. Among the Yorubas (South-West Nigeria), cold decoction of MCW is used as a natural antidote for oral gastric poisonings, infective hepatitis and other liver diseases. Its hepatoprotective activities were monitored by assaying for the serum aminotransferases, ornithine carbamoyl transferase and the toxicant-induced histopathological lesions in rat livers 24 hours post-induction. These enzymes are markers of acute hepatic injuries and their elevations are indications of acute liver injuries. Pretreatment of rats with graded doses (125 – 500 mg/kg) of MCW significantly attenuated the acute elevation of the liver enzymes and the hepatotoxin-induced histopathological lesions in the rat livers. The presence of two active natural antioxidants (flavonoids and alkaloids) in high concentrations in MCW may account for the hepatoprotective activities observed in this study. These results, thus, support the folkloric use of MCW for treatment of hepatic injuries resulting from acute gastric poisonings, infective hepatitis or other liver diseases.     

Hepatoprotective constituents in plants 15: protective effects of natural-occurring flavonoids and miscellaneous phenolic compounds as determined in an HepG2 cell cytotoxicity assay

In order to clarify the efficacy of natural-occurring hepatoprotective flavonoids and related miscellaneous compounds, we have investigated the hepatoprotective activity of 41 phenolic compounds on human liver-derived HepG2 cells and evaluated their structure-activity relationships. The hepatoprotective activity of catechin (cyanidanol), which has been used to treat chronic hepatitis, was almost equal to that of glycyrrhizin at 200 M. The structure-activity relationships of flavanol derivatives as revealed by this investigation suggest that (1) the configuration of the hydroxy group at C-3 does not affect the hepatoprotective activity; (2) the pyrogallol and catechol groups in the B-ring are almost comparable in terms of hepatoprotection; (3) the galloyl group is a key factor for enhancing hepatoprotective activity; (4) the free carboxyl group of gallic acid reduces hepatoprotective activity. The common structural features of the most potent hepatoprotective phenolic compounds are summarized.     

An isocoumarin with hepatoprotective activity in Hep G2 and primary hepatocytes fromAgrimonia pilosa

Phytochemical investigation of the aqueous extract of the roots of Agrimonia pilosa Ledeb. (Rosaceae), as guided by hepatoprotective activity in vitro, furnished two isocoumarins, agrimonolide (1) and agrimonolide 6-O-beta-D-glucoside (3), and (+)-catechin (2). Compound 1 showed hepatoprotective effects on both tacrine-induced cytotoxicity in human liver-derived Hep G2 cells and tert-butyl hydroperoxide-induced cytotoxicity in rat primary hepatocytes with EC50 values of 88.2 +/- 2.8 and 37.7 +/- 1.6 microM, respectively.     

Synthesis of Allylthiopyridazine Derivatives and Inhibition of Aflatoxin B<Subscript>1</Subscript>-Induced Hepatotoxicity in Rats

Five kinds of allylthiopyridazine derivatives were synthesized and their chemoprotective activities examined in rats exposed to aflatoxin B1-toxicant. Rats were pretreated with five allylthiopyridazine derivatives at daily oral doses of 50 mg/kg for 10 consecutive days, and during this period with one or three repeated doses of the potent hepatotoxin, aflatoxin B1. The hepatoprotective effects of the allylthiopyridazine derivatives against aflatoxin B1 (1 mg/kg, three times at intervals of 3 days, i.p., or at 3 mg/kg, once at final days, i.p.) administration were showed the significantly normal as compared with control in body and liver weights. Aspartate aminotransferase and alanine aminotransferase levels were markedly elevated after aflatoxin B1 administration, and pretreatment with allylthiopyridazine derivatives, before aflatoxin B1 administration, resulted in decreased levels of these enzymes. In addition, the allylthiopyridazine derivatives, K6 (3-methoxy-), K8 (3-chloro-), K16 (3-ethoxy-) and K17 (3-n-propoxy), induced elevated hepatic GSH levels. Four kinds of allylthiopyridazine derivatives investigated were effective against aflatoxin B1-induced hepatotoxicity.     

Chemopreventive effects of 2-(Allylthio)pyrazine

A series of organosulfur compounds were synthesized with the aim of developing chemopreventive compounds active against hepatotoxicity and chemical carcinogenesis. 2-(Allylthio) pyrazine (2-AP) was effective in inhibiting cytochrome P450 2E1-mediated catalytic activities and protein expression, and in inducing microsomal expoxide hydrolase and major glutathione S-transferases. 2-AP reduced the hepatotoxicity caused by toxicants and elevated cellular GSH content. Development of skin tumors, pulmonary adenoma and aberrant crypt foci in colon by various chemical carcinogens was inhibited by 2-AP pretreatment. Anticarcinogenic effects of 2-AP at the stage of initiation of tumors were also observed in the aflatoxin B₁ (AFB₁)-induced three-step medium-term hepatocarcinogenesis model. Reduction of AFB₁-DNA adduct by 2-AP appeared to result from the decreased formation of AFB₁-8,9-epoxide via suppression of cytochrome P450, while induction of GST by 2-AP increases the excretion of glutathione-conjugated AFB₁. 2-AP was a radioprotective agent effective against the lethal dose of total body irradiation and reduced radiation-induced injury in association with the elevation of detoxifying gene expression. 2-AP produces reactive oxygen speciesin vivo, which is not mediated with the thiol-dependent production of oxidants and that NF-κB activation is not involved in the induction of the detoxifying enzymes. The mechanism of chemoprotection by 2-AP may involve inhibition of the P450-mediated metabolic activation of chemical carcinogens and enhancement of electrophilic detoxification through induction of phase II detoxification enzymes which would facilitate the clearance of activated metabolites through conjugation reaction.