Hepatoprotective potential of petroleum ether leaf extract of Crossandra infundibuliformis on CCl4 induced liver toxicity in albino mice

ObjectiveTo analyze the hepatoprotective effect of the Crossandra infundibuliformis.MethodsHepatotoxicity was induced by carbon tetrachloride. Petroleum ether extract of dried leaves was administrated to mice for 7 days. The hepatoprotective effect of petroleum ether extract was evaluated by the assay of liver function biochemical parameters.ResultsThe result clearly indicates that petroleum ether extract showed significant hepatoprotection when compared with standard Silumarin.ConclusionsThe petroleum ether extract of the leaves of Crossandra infundibuliformis possess significant acute hepatoprotective activity. Thus further investigation on this species would bring a promising drug for liver disorders.     

The toxicity of a crude enzyme extract from Gliomastix murorum in Swiss Albino mice

A crude enzyme extract from a fungus, Gliomastix murorum, could be used in the synthesis of oligosaccharides that are essential to the food and drug industries. This extract may contaminate such products and lead to serious health problems. An investigation on the possible toxicity and mutagenic effect of the extract from this fungal isolate was carried out in Swiss Albino mice. One hundred and 50% of the crude enzyme extract were injected intraperitoneally into the mice every 2 days for 30 days. Normal saline (0.9%), cultivation medium, and cyclophosphamide (80 mg/kg body weight) were given to the control groups. The results indicated that the white blood cell count, serum creatinine, and uric acid of the treated mice were significantly higher than those of the controls (p<0.05), whereas the serum urea-N was lower. For the micronucleus test, mice treated with the extract, especially the group received 100% crude enzyme extract, showed a higher number of micronuclei in polychromatic erythrocytes, as compared to controls. Nevertheless, the micronucleus values were not as high as those found in mice treated with cyclophosphamide, the mutagenic agent. It can be concluded from the results that crude enzyme extract had minor toxic effects on various organ systems tested; more extensive investigation on the safe use of this extract is therefore necessary.     

Evaluation of antitumour activity of Calotropis gigantea L. root bark against Ehrlich ascites carcinoma in Swiss albino mice

ObjectiveTo investigate experimentally the possible antitumor effect of methanol extract (ME) of Calotropis gigantea L. (C. gigantean) root bark and its petroleum ether (PEF) and chloroform (CF) soluble fractions against Ehrlich ascites carcinoma (EAC) in Swiss albino mice.MethodsThe effects of ME (10 and 20 mg/kg), PEF (40 and 80 mg/kg) and CF (20 and 40 mg/kg) on the growth of EAC and life span of EAC bearing mice were studied. Hematological profile and biochemical parameters (SALP, SGPT and SGOT) were also estimated.ResultsResults of in vivo study showed a significant decrease in viable tumor cell count and a significant increase of life span in the ME and CF treated group compared to untreated one. The life span of ME and CF treated animals was significantly (P<0.05) increased by 43.90% (20 mg ME/kg) and 57.07% (40 mg CF/kg). ME and CF brought back the hematological parameter more or less normal level. ME and CF also restored the altered levels of serum alkaline phosphatase (SALP) and serum glutamate oxaloacetate transaminase (SGOT).ConclusionsMethanol extract (ME) of C. gigantea root bark and its chloroform soluble fraction (CF) possesses significant antitumor activity.     

Comparison of the subacute toxicity and efficacy of 3-hydroxypyridin-4- one iron chelators in overloaded and nonoverloaded mice

Five orally effective iron chelators of the 3-hydroxypyridin-4-one series have been administered intraperitoneally to iron-overloaded and nonoverloaded male mice at a dose of 200 mg/kg/24 h for a total of 60 days to investigate the effect on iron loading and toxicity. There was a significant reduction in hepatic iron at the end of the study in the iron-overloaded mice with all compounds studied using chemical iron quantitation (P less than .001) and with Perls' stain (P less than .01). Liver iron removal with the hydroxypyridinones ranged from 37% with CP20 to 63% with CP51, compared with 46% removal for desferrioxamine (DFO). There was no significant reduction in splenic or cardiac iron with any chelator. There were no deaths in iron-overloaded animals receiving any of the hydroxypyridin-4-ones, but significantly more deaths in the nonoverloaded groups as a whole (P less than .03). No weight loss was observed with any chelator. Significant reductions in hemoglobin and white cell count were observed with CP20(L1). No histologic abnormalities of kidney, spleen, bone marrow, or stifle joints were observed. Intracytoplasmic inclusion bodies were observed in the centrilobular hepatocytes of animals administered each of the hydroxypyridin-4-ones, while the DFO-treated and control groups showed no such changes.     

Clinico-pathological effects of Schistosoma mansoni infection associated with simultaneous exposure to malathion in Swiss outbred albino mice

To investigate whether infection of Swiss outbred mice with the digenetic fluke Schistosoma mansoni is influenced by exposure to environmental pollutants, experimentally infected mice were exposed to 200 and 400 mg/kg of malathion. Pathology of liver and spleen, worm burden and levels of key hematological, biochemical and liver enzymes parameters of these mice were evaluated and were compared with data from infected, unexposed mice, uninfected, exposed mice as well as with data from uninfected, unexposed mice. Oral administration of malathion to mice infected with 20, 40 or 60 S. mansoni cercariae adversely affect architecture of liver and spleen and critically alter hematological, biochemical, histological and hepatic enzymes parameters significantly more than the controls. Alterations observed in infected, exposed mice included (i) higher mortality rate; (ii) severe pathologies in liver and spleen; (iii) increased serum level of bilirubin and alanine aminotransferase/aspartate aminotransferase (ALT/AST) enzymes; (iv) decreased serum level of albumin and total proteins; and (v) decreased red blood cell count (RBC), lymphocytes, leucocytic count, and hemoglobin content. The number of recovered adult worms of S. mansoni or their oviposition capacity did not seem to be affected with malathion treatment. Statistical analysis revealed that the increase alteration in hepatic functions is correlated with increasing the number of S. mansoni cercariae and malathion doses. Such alterations were more significant in mice treated with the higher dose of malathion or infected with the largest numbers of S. mansoni cercariae. These data indicate that schistosomiasis can be exacerbated by simultaneous malathion exposure, which in turn adversely impact the clinical and pathological outcome of the disease.     

Tacrolimus toxicity due to drug interaction with mibefradil in a patient after liver transplantation.

A 54-year-old male liver transplant patient received mibefradil, a novel T-type calcium channel blocker, as antihypertensive treatment while he was on tacrolimus. He subsequently developed dizziness and fatigue of gradual onset as well as shoulder muscle ache. In addition, reversible impairment of renal function occurred with an increase in creatinine and potassium levels. Monitoring of tacrolimus levels, which had been in the desired range (5-8 ng/ml) until recently, revealed an increase to toxic level of 54 ng/ml. After discontinuation of mibefradil, tacrolimus levels returned to the normal range and all symptoms and clinical changes were reversible. Mibefradil and tacrolimus both are metabolized through the cytochrome--P-450 pathway. We suspect that drug interaction due to competitive inhibition of tacrolimus metabolism by mibefradil was responsible for these toxic effects. Therefore, special caution is recommended when administering tacrolimus with other drugs that carry the potential for pharmakokinetic interaction.     

Antioxidant and anti-inflammatory effects of mild hypothermia in the attenuation of liver injury due to azoxymethane toxicity in the mouse

Previous studies have demonstrated protective effects of mild hypothermia following acetaminophen (APAP)-induced acute liver failure (ALF). However, effects of this treatment in ALF due to other toxins have not yet been fully investigated. In the present study, the effects of mild hypothermia in relation to liver pathology, hepatic and cerebral glutathione, plasma ammonia concentrations, progression of encephalopathy, cerebral edema, and plasma proinflammatory cytokines were assessed in mice with ALF resulting from azoxymethane (AOM) hepatotoxicity, a well characterized model of toxic liver injury. Male C57BL/6 mice were treated with AOM (100 μg/g; i.p.) or saline and sacrificed at coma stages of encephalopathy in parallel with AOM mice maintained mildly hypothermic (35°C). AOM treatment led to hepatic damage, significant increase in plasma transaminase activity, decreased hepatic glutathione levels, and brain GSH/GSSG ratios as well as selective increases in expression of plasma proinflammatory cytokines. Mild hypothermia resulted in reduced hepatic damage, improvement in neurological function, normalization of glutathione levels, and selective attenuation in expression of circulating proinflammatory cytokines. These findings demonstrate that the beneficial effects of mild hypothermia in experimental AOM-induced ALF involve both antioxidant and anti-inflammatory mechanisms.     

The antioxidant and neuroprotective effects of the Psychotria camptopus Verd. Hook. (Rubiaceae) stem bark methanol extract contributes to its antiepileptogenic activity against pentylenetetrazol kindling in male Wistar rats

A substantial number of epileptic patients are resistant to the current medication thus necessitating the search for alternative therapies for intractable forms of the disease. Previous studies demonstrated the acute anticonvulsant properties of the methanol extract of the stem bark of Psychotria camptopus (MEPC) in rats. This study investigated the effects of MEPC on pentylenetetrazole-kindled Wistar rats. Kindling was induced by intraperitoneal injection of pentylenetetrazole (37.5 mg/kg) on every alternate day, 1 h after each daily oral pretreatment of rats (8?≤?n?≤?10) with MEPC (40, 80 and 120 mg/kg), vehicle or diazepam (3 mg/kg) for 43 days. The kindling development was monitored based on seizure episodes and severity. Rats’ brains were collected on day 43 for the determination of oxidative stress parameters. The histomorphological features and neuronal cell viability of the prefrontal cortex (PFC) and hippocampus were also assessed using H&E and Cresyl violet stains. Chronic administration of pentylenetetrazole time-dependently decreased the latency to myoclonic and generalized seizures, and increased seizure scores and the number of kindled rats. MEPC and diazepam significantly increased the latencies to myoclonic jerks and generalized tonic-clonic seizures. These substances also reduced seizure score and the number of rats with PTZ-kindling. MEPC improved glutathione status and decreased lipid peroxidation in the brains of kindled rats. MEPC also exhibited neuroprotection against pentylenetetrazole-induced hippocampal and PFC neuronal damages. These results suggest that P. camptopus has antiepileptogenic activity, which might be related to the augmentation of antioxidant and neuroprotective defense mechanisms, and further confirm its usefulness in the management of epilepsy.

     

行气活血饮对慢性乙型肝炎肝纤维化肝郁脾虚证患者铁代谢的影响

目的:观察行气活血饮对慢性乙型肝炎肝纤维化肝郁脾虚证患者铁代谢的影响。方法:65例患者随机分为两组,治疗组34例,对照组31例,治疗组患者用行气活血饮治疗,对照组患者口服复方丹参片。观察比较患者治疗前后血清透明质酸、Ⅲ型前胶原、IV型胶原、层粘连蛋白变化及血清铁、铁蛋白、转铁蛋白水平变化。结果:治疗组患者治疗后血清透明质酸、IV型胶原、血清铁、血清铁蛋白水平较治疗前下降,两组相比差异有显著性意义。治疗组总有效率为85.3%,显著高于对照组58.1%(P<0.05)。结论:行气活血饮有一定的抗肝纤维化作用,对血清铁、血清铁蛋白有显著抑制作用。     

罗格列酮对日本血吸虫病肝纤维化小鼠肝组织核因子-κB和过氧化物酶体增殖物激活受体γ表达的影响

目的:观察日本血吸虫病肝纤维化小鼠肝脏肝组织核因子-κB(NF-κB)的活性和过氧化物酶体增殖物激活受体γ(PPARγ)的表达,及PPARγ配体罗格列酮对其表达的影响.方法:50只昆明小鼠,随机分为正常对照组、感染对照组、吡喹酮治疗组、罗格列酮治疗组及罗格列酮加吡喹酮治疗组.除正常对照组外,其余各组均建立血吸虫病肝纤维化小鼠模型.用HE染色观察肝组织光镜下的病理改变.用Western blot方法,实时荧光定量PCR反应观察小鼠肝组织NF-κB的活性变化与PPARγmRNA的表达.结果:罗格列酮加吡喹酮治疗组小鼠肝脏的炎性反应和纤维化病理改变较其他模型组轻(P＜0.05).感染对照组NF-κB活性(141.11±15.37)最强,明显高于其余各组(正常对照组:78.89±18.12;吡喹酮组:112.89±20.17:罗格列酮组:108.89±20.47;罗格列酮加吡喹酮组:88.89±19.34)(P＜0.05).感染对照组[-27.315±(-6.348)].及吡喹酮治疗组[-25.647±(-5.694)]PPARγ mRNA表达较正常对照组[-16.557±(.3.022)]及罗格列酮治疗组[-18.217±(-4.498)]、罗格列酮加吡喹酮治疗组[-18.212±(-3.909)]显著减弱(P＜0.05).结论:PPARγ及NF-κB在血吸虫病肝纤维化形成中起一定作用.PPARγ配体罗格列酮有明显的抗日本血吸虫病肝纤维化效应,其抗纤维化机制与PPARγ配体激活PPARγ表达的同时抑制NF-κB的活性有关.     

罗格列酮对血吸虫病肝纤维化小鼠肝脏TGF-β1和α-SMA表达的影响

目的 研究过氧化物酶体增殖物激活受体γ (PPARγ)的配体罗格列酮对日本血吸虫病肝纤维化小鼠肝脏转化生长因子β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)含量的影响.方法 将30只日本血吸虫病肝纤维化小鼠均分3组对照组,吡喹酮治疗组和罗格列酮治疗组.对照组不作任何治疗.吡喹酮治疗组用吡喹酮500 mg/(kg·d)灌胃治疗2 d,罗格列酮治疗组在吡喹酮治疗2 d后再用罗格列酮4 mg/(Kg·d)灌胃治疗6周.应用HE染色,免疫组化法及多媒体病理图文定量分析,观察罗格列酮治疗血吸虫病肝纤维化小鼠肝脏的病理改变及TGF-β1和α-SMA表达的变化.结果 罗格列酮能显著抑制血吸虫病小鼠肝脏纤维组织的增生,降低肝脏TGF-β1及α-SMA的表达.结论 PPARγ配体罗格列酮有明显的抗日本血吸虫病肝纤维化作用,其抗纤维化机制与其抑制肝星状细胞(HSC)活化、抑制其表达α-SMA及分泌TGF-β1密切相关.