西米替丁降低吡喹酮在大鼠体内的消除

研究了西米替丁对吡喹酮(praziguantel PQT)在大鼠体内消除的影响.结果表明西米替丁100 mg/kg,ip×2能使静脉注射和口服 PQT 后的清除率分别降低60%和69%。西米替丁亦降低大鼠肝血流量58%,并抑制 PQT 在大鼠肝微粒的体内代谢,抑制率55%。静脉注射吡喹酮清除率的降低可归于西米替丁降低肝血流的结果,而口服 PQT 清除率的降低主要可能与西米替丁对肝药酶的抑制有关。     

氯解磷定在急性辛硫磷中毒大鼠体内药代动力学

目的　探讨氯解磷定 (PAM Cl)在急性辛硫磷中毒大鼠体内药代动力学性质变化和PAM Cl对乙酰胆碱酯酶 (AChE)的复能作用 ,为治疗辛硫磷中毒合理利用PAM Cl提供科学依据。方法　给大鼠腹腔注射 80mg kgPAM Cl,采用高效液相色谱法测定PAM Cl血浆浓度。PAM Cl的血药 时间曲线用 3P97拟合。改良Ellman法测AChE活力。结果　PAM Cl在急性辛硫磷中毒大鼠和正常大鼠体内血药浓度经时过程均符合一室开放模型。与正常大鼠相比 ,PAM Cl在急性辛硫磷中毒大鼠体内血药最高峰浓度〔(2 2 85± 2 5 5 ) μg ml〕和血药 时间曲线下面积〔(13 0 4 0 2± 10 9 87) μg (min·ml)〕明显增高 (P <0 0 5 ) ,全身清除率〔(0 0 6± 0 0 1)L (min·kg)〕和中室表观分布容积〔(2 66± 0 3 7)L kg〕显著降低 (P <0 0 5 )。结论　PAM Cl在急性辛硫磷中毒大鼠体内的排泄较正常大鼠慢。     

胃舒散对四氯化碳慢性肝损伤大鼠的保护作用

目的　观察胃舒散对四氯化碳 (CCl4)所致大鼠慢性肝损伤的影响。方法　采用CCl4诱导大鼠慢性肝损伤模型 ,测定血清丙氨酸氨基转移酶 (ALT)、天门冬氨酸氨基转移酶 (AST)、血清白蛋白 (ALB)、透明质酸(HA)、肝组织羟脯氨酸 (Hyp)含量 ,并进行肝脏病理组织学检查。结果　CCl4慢性肝损伤大鼠血清ALT、AST、HA、肝组织Hyp含量升高 (与正常组比较P <0 0 1～ 0 0 0 1) ,血清ALB含量降低 (与正常组比较P <0 0 1) ,肝细胞坏死程度和肝组织纤维化程度显著增加 ,造模成功。胃舒散能显著降低血清ALT、AST、HA、肝组织Hyp含量(与模型组比较P <0 0 5～ 0 0 1) ,升高血清ALB值 (与模型组比较P <0 0 5～ 0 0 1) ,并能使肝细胞坏死程度和肝组织纤维化程度减轻。结论　胃舒散对大鼠CCl4慢性肝损伤有明显的保护作用。     

茵陈蒿汤对实验性肝纤维化大鼠肝细胞的保护作用及超微结构观察

目的 :观察茵陈蒿汤对实验性肝纤维化大鼠肝细胞损伤的保护作用及超微结构变化。方法 :Wistar大鼠被随机分为 4组 :正常对照组、CCl4 模型组、秋水仙碱组、茵陈蒿汤组。采用 4 0 % CCl4 皮下注射制备大鼠实验性肝纤维化模型 ,观察茵陈蒿汤对肝功能、肝脏组织病理变化和超微结构变化的影响。结果 :茵陈蒿汤能明显改善实验性肝纤维化大鼠的肝功能、肝脏组织病理变化和超微结构变化 ,与 CCl4 组比较差异有显著性意义 (P <0 .0 5 )。结论 :茵陈蒿汤对 CCl4 损伤性肝细胞有保护作用 ,可改善肝功能 ,对线粒体等细胞器的损伤具有保护作用     

混合蔬菜汁对四氯化碳染毒大鼠脂质过氧化和转氨酶活性的影响

目的　以四氯化碳 (CCl4 )染毒大鼠为肝损伤动物模型 ,观察了胡萝卜、西红柿、甘蓝、莴苣、芹菜、洋葱、茄子、菠菜等 8种蔬菜的混合菜汁对大鼠脂质过氧化和转氨酶活性的影响 ,并探讨其可能机制。方法　将 110只大鼠随机分为 5组 :对照组、CCl4 组、CCl4 +提前给予混合蔬菜汁组、CCl4 + 10 0 %混合蔬菜汁组、CCl4 + 5 0 %混合蔬菜汁组。CCl4 按0 3 5ml kg 1次性腹腔注射 ,混合蔬菜汁按 1ml 10 0g体重灌胃。分别于染毒后第 1天、第 2天、第 7天将各组大鼠随机处死 6只 ,测定血清丙氨酸转氨酶 (ALT)、天冬氨酸转氨酶 (AST)活性 ,血清脂质过氧化 (LPO)水平 ,血清铜蓝蛋白 (CP)含量 ,血清、肝匀浆超氧化物歧化酶 (SOD)活性 ,血清、肝匀浆过氧化氢酶 (CAT)活性。结果　各染毒组肝 体比值增加 ,血清ALT、AST活性增高 ,LPO水平升高 ,各混合蔬菜汁组血清AST、ALT活性均低于CCl4 组 ,以 5 0 %组血清AST、ALT活性最低。结论　在染毒同时给予 5 0 %混合蔬菜汁 ,对CCl4 引起LPO有明显的拮抗作用 ,可能与其能清除·CCl3有关。     

虫草菌丝对实验性肝硬化大鼠肝组织胰岛素酶活性的影响

目的 :探讨虫草菌丝对实验性肝硬化大鼠肝组织匀浆上清液胰岛素酶活性的动态影响及其可能机制。方法 :以CCl4诱导大鼠肝硬化模型 ,设立正常组、模型组和虫草组。正常组于实验开始时便处死大鼠 ,而后 2组则于造模 3 ,6,9wk分批处死 ,取血及肝组织标本。生化法测定血清丙氨酸转氨酶(ALT)、清蛋白 (ALB)含量 ,放射免疫法测定血清透明质酸 (HA)、血清胰岛素 (INS)含量及肝组织匀浆上清液的胰岛素酶活性。结果 :(1 ) 3 ,6wk虫草组大鼠血清ALT ,ALB及HA含量与对应模型组差异无显著意义 (P >0 .0 5 ) ,9wk虫草组大鼠血清ALT ,HA含量显著低于对应模型组 (P <0 .0 5 ) ,而其血清ALB含量则显著高于对应模型组 (P<0 .0 5 ) ;(2 ) 3wk虫草组及模型组大鼠血清INS水平及肝组织胰岛素酶活性与正常组大鼠差异无显著意义 (P >0 .0 5 ) ,6,9wk虫草组及模型组大鼠血清INS水平显著高于正常组 (P <0 .0 5 ) ,而对应的肝组织胰岛素酶活性则显著低于正常组 (P <0 .0 5 ,或P <0 .0 1 ) ;(3 ) 3 ,6,9wk虫草组大鼠血清INS水平及肝组织胰岛素酶活性与对应模型组差异无显著意义(P >0 .0 5 )。结论 :虫草菌丝可减轻CCl4对肝细胞的损伤 ,并可抑制肝纤维化 ;造模 6wk后实验性肝硬化大鼠肝组织胰岛素酶活性开始降低 ,血清INS含量开始升高     

他克莫司在溃疡性结肠炎模型大鼠体内的药代动力学研究

目的:考察他克莫司(FK506)在葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎(UC)模型大鼠体内的药代动力学特点。方法:将12只大鼠随机分为UC组和正常组各6只,UC组给予5%DSS连续自由饮用7 d诱导建立UC模型,第8天分别给予两组大鼠灌胃FK506 1 mg/kg,于给药前和给药后不同时间点采血,测定FK506血药浓度,比较分析两组大鼠主要药代动力学参数。结果:与正常组相比,UC组体内的FK506暴露强度增加,AUC_0-t增加了44.06%,半衰期延长了1.85 h(近50%),体内滞留时间(MRT_0-∞)延长了37.0%,清除率下降了32.25%(P均<0.05)。结论:FK506在大鼠体内的药代动力学会受到UC的影响,导致FK506代谢下降,半衰期延长,暴露强度增加,可能与UC影响P糖蛋白和CYP3A酶活性有关。     

小柴胡汤抗肝纤维化的形态学和血清学实验研究

目的 :观察小柴胡汤对肝纤维化形态结构和血清学的影响及作用机理。方法 :采用大鼠四氯化碳 (CCl4 )中毒性肝纤维化模型 ,实验分正常对照、病理模型对照、预防和治疗 4组。采用光镜、电镜观察形态学改变 ,并检测血清生物化学的变化。结果 :与 CCl4 组相比 ,预防组和治疗组 AL T、AST均显著降低 (P <0 .0 1) ,AL B显著增加 (P <0 .0 5 )。结论 :小柴胡汤有明显的改善肝功能和抗肝纤维化的作用。     

小柴胡汤和柴胡—黄芩含药血清对CCl_4损伤肝细胞的影响

目的　建立CCl4肝细胞损伤模型 ,考察小柴胡汤及柴胡—黄芩配方含药血清对CCl4损伤肝细胞的保护作用。方法　制备小柴胡汤及柴胡—黄芩配方的大鼠含药血清 ,体外10mol·L-1CCl4诱导肝细胞损伤模型 ,观察体积分数为 0 1的含药血清对损伤肝细胞增殖率、GPT、细胞形态学以及凋亡率的影响。结果　与正常组比较 ,模型组肝细胞增殖率降低 (P <0 0 1) ,细胞培养上清液中GPT含量升高 (P <0 0 1) ;与模型组比较 ,小柴胡汤及柴胡—黄芩配方组的肝细胞增殖率提高 (P <0 0 1) ,细胞培养上清液中GPT含量降低 (P <0 0 1)。倒置显微镜和Giemsa染色观察到模型组肝细胞存在着明显的坏死和凋亡 ,小柴胡汤及柴胡—黄芩配方的凋亡细胞明显减少。与正常组比较 ,CCL4模型组细胞凋亡增高 (P <0 0 1) ;与模型组比较 ,柴芩组和小柴胡汤全方组的细胞凋亡率降低 (P <0 0 1)。结论　小柴胡汤及柴胡—黄芩配方含药血清对体外CCl4诱导的肝细胞损伤有保护作用。CCl4引起的肝损伤同时存在着明显的凋亡和坏死 ,小柴胡汤及柴胡 -黄芩配方可能具有抗CCl4诱导的肝细胞凋亡的作用。     

丹参与黄芪配伍对实验性肝纤维化作用的观察

目的 :观察丹参与黄芪配伍提取物对大鼠肝纤维化的作用及机制。方法 :采用 CCl4 复制大鼠肝纤维化模型 ,同时予以丹参与黄芪配伍提取物灌胃治疗 ,观察大鼠血清丙氨酸氨基转移酶 (AL T)、天门冬酸氨基转移酶 (AST)、白蛋白 (Alb)、肝组织羟脯氨酸 (Hyp)含量及肝组织病理改变。结果 :模型组大鼠 AL T、AST、Hyp显著升高 ,Alb显著降低 ,肝纤维化病变明显 ,给药组 AL T、AST、Hyp明显降低 ,Alb明显升高 ,与模型组比较 ,差异有显著性 (P <0 .0 1或 P <0 .0 5 ) ;并能明显减轻大鼠肝细胞损害和胶原纤维增生的程度。结论 :丹参与黄芪配伍提取物有较好的保护肝功能和防治肝纤维化作用     

Blood clearances of 99mTc-phytate and indocyanine green in carbon tetrachloride treated dogs.

The comparative study of the blood clearances of 99mTc-phytate (99mTc-P) and indocyanine green (ICG) was carried out in dogs with hepatic injury induced by carbon tetrachloride (CCl4), and the blood clearance of 99mTc-P or ICG was compared with the levels of serum transaminase and bilirubin. The blood clearances of 99mTc-P and ICG in dogs decreased with increase in doses of CCl4 and with elapsed time after CCl4 administration. The decreases were correspondent to the increase in serum transaminase activity and bilirubin level. The blood clearance test of 99mTc-P in dogs showed a equal degree of sensitivity and a higher degree of accuracy for the acute hepatic dysfunction induced by CCl4 as compared with the blood clearance test of ICG.     

The effect of chronic captopril administration on hepatic blood flow of the rat

The effect of chronic captopril administration on indocyanine green (ICG) clearance and hepatic extraction has been studied in the rat using the intact liver for ICG clearance and the isolated perfused liver for ICG extraction. The captopril was added to the drinking water to give a calculated daily intake from 0-45 mg kg-1. Hepatic clearance of ICG was dose related from 16.5 +/- 2.4 (control) to 7.2 +/- 1.6 mL min-1 kg-1, respectively. The hepatic extraction of ICG was not significantly different (37 +/- 6%) from the control value in groups on 4 and 45 mg kg-1 daily. Since ICG clearance and extraction are dependent on hepatic blood, a change in ICG clearance without a change in the extraction reflects a similar change in the hepatic blood flow. This remained unchanged at daily captopril intakes of 1 and 4 mg kg-1 and decreased when the daily intake was 10 mg kg-1 or higher. If these results in the rat are applicable to man, the chronic administration of therapeutic doses of captopril (0.5-2 mg kg-1) will not affect the hepatic blood flow.     

Effects of gomisin A on liver functions in hepatotoxic chemicals-treated rats

The effects of gomisin A, which is a lignan component of schizandra fruits, on liver functions in various experimental liver injuries and on bile secretion in CCl4-induced liver injury were studied. Gomisin A weakly accelerated the disappearance of plasma ICG by itself at a high dose (100 mg/kg, i.p.). All of the hepatotoxic chemicals used in this study inhibited the excretion of ICG from plasma. Gomisin A showed a tendency to prevent the delays of the disappearance of plasma ICG induced by CCl4, d-galactosamine and orotic acid, but not that by ANIT. Bile flow and biliary outputs of total bile acids and electrolytes (Na+, K+, Cl- and HCO3-) were decreased in CCl4-treated rats. Gomisin A maintained bile flow and biliary output of each electrolyte nearly to the level of the vehicle-treated group, but did not affect biliary output of total bile acids. These findings suggest that gomisin A possesses a liver function-facilitating property in normal and liver injured rats and that its preventive action on CCl4-induced cholestasis is due to maintaining the function of the bile acids-independent fraction.     

Effect of chlorpromazine on hepatic transport of indocyanine green in rats

The effect of chlorpromazine hydrochloride (CPZ) on the hepatic transport of indocyanine green (ICG) was studied in the rat, in an attempt to elucidate the mechanisms of hepatotoxicity of CPZ in vivo, by comparing the pharmacokinetic parameters of ICG after bolus and chronic administration of CPZ. Delays were shown in both plasma disappearance and biliary excretion of ICG in the CPZ-treated rats (10 and 15 mg/kg intraportal bolus administration). Significant decreases were observed in the pharmacokinetic parameters, V₂ and total body clearance (CL_tot) in CPZ 10 mg/kg treated rats and k₃₄, V₂ and CL_tot in CPZ 15 mg/kg treated rats, while a significant increase was observed in k₂₁ in both CPZ-treated groups; V₁ was not altered. The apparent liver-to-plasma concentration ratio (K_p,app) of ICG at 50 min after i.v. administration was decreased significantly in CPZ 15 mg/kg treated rats when compared to control rats, suggesting an alteration in the distribution of ICG to the liver by CPZ. Bile flow rates decreased immediately after bolus intraportal administration of CPZ in both CPZ-treated groups, and they then returned progressively to the basal levels. The output of bile acids was also inhibited by CPZ in a time-dependent and reversible manner and the bile acid independent fraction of bile flow was decreased significantly in both CPZ-treated groups. Chronic treatment with CPZ (10 or 20 mg/kg, i.p., per day for 3 weeks) did not alter either the pharmacokinetic parameters or the bile secretion profile of ICG, although there were significant decreases in body and liver weights in CPZ-treated groups. This may have been due to the rapid metabolism and excretion of CPZ in the rat when compared to humans. It is proposed that the acute toxic effect of CPZ on hepatic transport of ICG in the rat may be due mainly to the time-dependent and reversible cholestasis induced by CPZ, and that chronic treatment with CPZ may not alter the hepatic transport of ICG in the rat.     

Effect of 2-methylaminoethyl-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2-carboxylic acid-2'-carboxylate monohydrochloride (DDB-S) on indocyanine green (ICG) clearance in rats

The clearance of ICG, a known hepatic blood flow marker was investigated in rats in order to examine whether DDB-S influences hepatic blood flow. The effect of DDB-S on the protein binding and blood-to-plasma partition of ICG was measured. The steady-state plasma concentration of ICG was monitored before and after co-administration of various concentration of DDB-S, and ICG clearance was estimated from the steady-state concentration and the infusion rate of ICG. There was no significant difference in protein binding and blood-to-plasma partition of ICG with and without addition of DDB-S (10, 20, and 40 microg/mL). When ICG was infused into DDB-S pretreated rats, the steady-state concentrations of ICG decreased and the calculated ICG clearance increased. However, no dose-dependency of ICG Css on DDB-S Css was observed. Since DDB-S did not affect the protein binding and blood-to-plasma partition of ICG, the increased clearance of ICG with co-administration of DDB-S seems to be due to the increased hepatic blood flow by DDB-S.     

Development of dosage design of hepatic metabolizing drugs using serum albumin level in chronic hepatic failure

We have previously reported good correlations among serum aminotransferase (AST) activity, metabolic enzyme activity of CYPs, and total clearance (CL(tot)) of probe drugs in rats with acute hepatic failure induced by CCl4. In this study, we searched for new biochemical indicators that correlate with hepatic function and tried to simulate appropriate drug dosage in chronic hepatic failure. Model rats were prepared by administration of CCl4 (1 ml/kg, s.c., 3 times/week) and used at 48 h after the last administration. Serum albumin concentration was time-dependently decreased and correlated well with 3 major biologic determinants of drug clearance, hepatic blood flow (HBF), intrinsic clearance (CL(int)), and the unbound fraction of drugs in plasma (fp) after intravenous administration of cyclophosphamide, tolbutamide, zonisamide, and chlorzoxazone (as probe drugs for low hepatic extraction) and propranolol and lidocaine (as high-hepatic extraction drugs). By calculating these parameters based on prediction equations by the level of albumin, CL(tot) was obtained. As a result of having evaluated this model using administration of cyclosporin, there was a statistically significant relationship between predicted CL(tot) and observed CL(tot). In conclusion, the value of serum albumin level is a useful parameter that correlates well with chronic hepatic function. We have shown that this quantitative administering design using serum albumin level can predict appropriate dosages of hepatic metabolizing drugs in chronic hepatic failure.     

Effects of Sho-saiko-to extract and its components, Baicalin, baicalein, glycyrrhizin and glycyrrhetic acid, on pharmacokinetic behavior of salicylamide in carbon tetrachloride intoxicated rats.

To elucidate the effects of Sho-saiko-to extract and its components, baicalin, baicalein, glycyrrhizin and glycyrrhetic acid, against the effects of longer periods of acute hepatic injury induced by CCl4, we measured serum ALT activity in male Wistar rats for five days after ip administration of CCl4 (0.2 ml/kg), and examined the daily changes of the pharmacokinetic behavior of salicylamide (SAM) for five days. Serum ALT activity rose to a maximum level within a day after administration of CCl4 and then decreased to the control level after three. Sho-saiko-to extract and its components could suppress this acute change in serum ALT activity to less than 50% of CCl4 alone. However, the pharmacokinetics of SAM showed that liver function recovers in a biphasic manner, so that plasma clearance (CL) decreased significantly at days 1 and 3 after administration of CCl4 (P<0.05). We concluded that the CL change at day 1 corresponds to the acute action of CCl4 intoxication, and that the change at day 3 is effect of physiologically reduced liver function due to the liver regeneration for tissue repair after the CCl4 hepatic injury. Sho-saiko-to extract and its components were shown to suppress acute hepatic injury induced by CCl4, and to bring about an early recovery in liver function.     

Thermal Injury Decreases Hepatic Blood Flow and the Intrinsic Clearance of Indocyanine Green in the Rat

The influence of severe thermal injury (full-thickness burns involving 50% of the body surface area) on hepatic blood flow in the rat was assessed using the tricarbocyanine dye indocyanine green (ICG). In a randomized crossover fashion, rats received sequential infusions of ICG through both the femoral vein and the portal vein, allowing the estimation of total hepatic plasma clearance and trans-hepatic extraction of the dye. These two parameters, along with the hematocrit, were used to calculate intrinsic hepatic clearance of ICG and hepatic blood flow. Animals were examined at 0 (control), 0.5, 12, or 24 hr following infliction of scald burns. Hepatic blood flow was decreased significantly by 0.5 hr postburn and remained approximately 20% below normal throughout the remainder of the study. The intrinsic efficiency of the liver in removing ICG from the systemic circulation was also decreased by thermal injury. The potential mechanisms involved in these two physiologic perturbations are discussed.     

Pharmacokinetics of phenol red in rat models of liver damage prepared by liver targeting of carbon tetrachloride

Animal models prepared by treatment with carbon tetrachloride (CCl(4)) have been used to examine drug disposition in hepatic disorder. However, previous studies demonstrated that systemic administration of CCl(4) impaired not only hepatic but also renal function. We recently reported that application of CCl(4) to the rat liver surface produced hepatic damage without impairing renal function. In the present study, we examined the pharmacokinetics of phenol red in our developed rat model. The rats treated with CCl(4) by liver surface application exhibited decreases in the biliary clearance of phenol red in comparison with normal rats from 0.54+/-0.03 to 0.31+/-0.06 ml/min, suggesting hepatic damage. In these rats, the renal clearance of phenol red did not decrease (0.50+/-0.16 ml/min vs. 0.46+/-0.07 ml/min in normal rats). On the other hand, oral and intraperitoneal treatments with CCl(4) reduced not only the biliary clearance of phenol red (0.34+/-0.03 ml/min in p.o. treated rats, 0.18+/-0.01 ml/min in i.p. treated rats) but also the renal clearance (0.26+/-0.05 ml/min in p.o. treated rats, 0.18+/-0.06 ml/min in i.p. treated rats) as compared with normal rats. These findings indicate that the rat model of liver damage prepared by liver surface application of CCl(4) is useful to investigate the effects of hepatic disorder on the pharmacokinetics of drugs.     

Effect of colchicine on hepatobiliary function in CCl4 treated rats.

A number of toxic chemicals affect the biliary excretory function of liver. Organochlorines and halomethanes are known to enhance bile flow. Despite the demonstration that a diversity of agents modify biliary function, the mechanism by which these chemicals manifest this effect is not fully understood. This study was designed to assess the effect of colchicine (0.1, 1.0, or 2.5 mg/kg, i.p., in saline) administration on biliary excretory function 6 and 24 hr later. Additionally, the effect of colchicine (1 mg/kg, i.p. in saline) pretreatment in rats 2 hr prior to the administration of a single low dose of CCl4 (100 microL/kg, i.p., in corn oil) or corn oil alone (1 mL/kg, i.p.) on hepatic biliary excretory function was also assessed at 6 and 24 hr after the last treatment. The hepatotoxicity was evaluated by serum enzymes, alanine and aspartate aminotransferases, and histopathological alterations of the liver. Biliary excretion of intravenously administered phenolphthalein glucuronide (PG) was assessed in bile duct cannulated anesthetized rats. Only the highest dose of colchicine (2.5 mg/kg) resulted in detectable liver injury as revealed by elevations of serum transaminases. While the lowest dose of colchicine (0.1 mg/kg) did not influence bile secretion, the two higher doses caused a slight choleretic effect at 24 hr. The highest dose caused a transient inhibition of bile flow, but this effect was no longer evident at 6 hr. Biliary excretion of PG was inhibited significantly by colchicine within 6 hr after administration, an effect that was also persistent at 24 hr. Colchicine at a 1 mg/kg dose did not cause any adverse effect on hepatobiliary function. Therefore, for the interactive toxicity study with CCl4, 1 mg colchicine/kg was chosen as a moderate dose which did not cause any significant adverse effect on hepatobiliary function. Biliary excretion of PG was significantly lower in rats at 6 and 24 hr after the combination treatment with colchicine + CCl4 than in rats receiving either CCl4 or colchicine alone. In contrast, rats receiving CCl4 alone or colchicine + CCl4 showed a significant increase in cumulative bile flow at 6 hr, whereas, at 24 hr, the bile flow was increased significantly in rats receiving colchicine regardless of CCl4 treatment. The data suggest that colchicine pretreatment leads to significant inhibition of hepatobiliary excretion in CCl4 treated rats. Serum alanine transaminase and aspartate transaminase levels were elevated significantly after the colchicine + CCl4 combination, indicating hepatic injury.(ABSTRACT TRUNCATED AT 400 WORDS)