Possible antiosteoporotic mechanism of Cicer arietinum extract in ovariectomized rats

Objective: The present study aimed to throw the light on the anti-osteoprotic mechanism of Cicer arietinum extract (CAE) seeds against ovariectomized (OVX) rats. Methods: Seventy female rats were divided into two groups. The first group (14 rats/group) represented normal rats (Sham operated) while the second group (56 rats/group) underwent bilateral ovariectomy (OVX). After one week of recovery from ovariectomy surgery, the second group was randomly subdivided into 4 subgroups (14 rats/ each subgroup). The rats administered orally; distilled water (vehicle) (1^st subgroup), Cicer arietinum extract (CAE) (500 or 1000 mg/kg body weight/day) (2^nd and 3^rd subgroups), alendronate (6.5 mg/kg mg/kg body weight) as a positive control one time/week (4^rh subgroup), daily for 10 weeks. Results: The present study demonstrated that ovariectomy caused significant decrease in bone mineral; density (BMD) and content (BMC), Bone-specific alkaline phosphatase (BALP), calcium (Ca), phosphorus (P), parathyroid hormone (PTH) and calcitonin levels. Furthermore, ovariectomy induced significant elevation of tartrate-resistant acid phosphatase 5b (TRAP 5b) and receptor activator of nuclear factor (NF-kappa β) ligand (RANKL) concentration. Conversely, osteoprotegerin (OPG) and OPG/RANKL ratio were decreased following ovariectomy. The present work suggests that CAE has antiosteoporotic action against ovariectomy effects and its activity may results from its phytochemical and/or phytoestrogen contents. Conclusion: The ongoing study speculates that the CAE exerts its action through regulation of RANK/RANKL/OPG system. As, CAE not only promotes osteoblast differentiation, but also up-regulates OPG and downregulates RANKL secretion in osteoblasts, subsequently prevents bone loss and osteoporosis.     

Kupffer cell phagocytosis blockade decreases morbidity in endotoxemic rats with obstructive jaundice

OBJECTIVE AND DESIGN: The consequences of Kupffer cell phagocytosis blockade were studied in endotoxemic rats with obstructive jaundice. MATERIAL OR SUBJECTS: 159 male Wistar rats. TREATMENT: Obstructive jaundice was induced by bile duct ligation (BDL). Gadolinium chloride (1 mg/100 g iv) was given 6 days after BDL to inhibit Kupffer cell activity and the animals were challenged with 1 microg/g endotoxin 24 h later. METHODS: Endotoxin sensitivity, tumor necrosis factor-alpha and interleukin-6 production were studied, liver and lung injury were assessed by neutrophil infiltration assay, tissue adenosine triphosphate, aspartate aminotransferase, alanine aminotransferase level determinations and histology, respectively. For statistics non-parametric methods were used. RESULTS: BDL sensitized the animals to endotoxin, increased endotoxin-induced tumor necrosis factor-alpha and interleukin-6 production and reduced ATP contents of the liver and the lung. Kupffer cell blockade significantly increased the resistance against endotoxin, diminished the inflammatory cytokine release and reduced endotoxin-induced tissue injury in BDL animals. CONCLUSION: Attenuation of Kupffer cell function decreases endotoxin-induced lethality and morbidity in obstructive jaundice.     

Cholera toxin-induced fluid secretion in rat gut ligated loops: influence of bile from normal or cholera toxin-immunized rats.

Fresh normal rat bile premixed with cholera toxin (CT) did not significantly affect the CT-induced fluid accumulation in rat jejunal ligated loops. Bile from rats intrajejunally (i.j.) immunized three times with CT definitely inhibited CT-induced fluid secretion. Bile duct ligature (BDL) for 1-4 days in unimmunized rats, in contrast with mice, did not significantly affect subsequent CT-elicited fluid secretion in their ligated loops. BDL for 4 days in rats i.j. immunized with CT, only slightly decreased the CT-neutralizing ability of their gut loops. Passive transfer during 24 hr of bile from i.j.-immunized rats, but not from normal rats, into gut of normal recipient rats with BDL, significantly protected loops made in such recipients. The affinity-purified antibodies of immune bile, mixed with CT, neutralized its effect. Our data show that, unlike mice, rat bile acids are not required for expression of the CT effect in gut loops. In addition, bile from i.j.-immunized rats contains enough anti-CT antibodies to be protective on its own, but is not necessary for substantial gut protection against CT in i.j.-immunized BDL rats. Our results confirm a major and complementary role of both biliary and intestinal secretory IgA antibodies in protection of the rat gut mucosa against CT-induced fluid secretion.     

Chronic bile duct obstruction induces changes in plasma and hepatic levels of cytokines and nitric oxide in the rat.

Chronic bile duct ligation (BDL) is a useful model of cirrhosis. However, its parallel plasma and liver changes in levels of cytokines and nitric oxide (NO), involved in liver damage, remain unknown. The aims of this work were to quantify both the plasma and hepatic levels of five cytokines and NO in cirrhotic rats, 28 days after bile BDL, and to analyze their relationship with liver damage markers. One group of male Wistar rats was bile duct ligated and another group was sham operated, both groups were sacrificed 28 days after BDL. Plasma and liver cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, -1beta, -10 (IL-6, -1beta, -10) and interferon-gamma (IFN-gamma), were measured by ELISA. Plasma and hepatic NO was determined as NO(2)(-)+NO(3)(-) by an enzymatic method. Alkaline phosphatase, gamma-glutamyl transpeptidase, alanine aminotransferase and bilirubins were determined in plasma. Collagen, lipid peroxidation and glycogen were quantified in liver. Two histopathological staining techniques were performed. BDL-induced cirrhosis was corroborated by the elevated liver damage markers and histopathological analysis. Chronic BDL significantly increased (P<0.05) most of plasma and hepatic cytokine levels and diminished the hepatic IFN-gamma amount. NO was increased in both tissues, but such change was only significant in plasma. Biliary cirrhosis produces interesting changes in plasma and hepatic levels of cytokines and NO. This finding in chronic BDL model in rats has not been previously described in both tissues for such cytokines and NO. Cytokines and NO imbalance favor establishment and perpetuation of cirrhosis.     

Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction in growing animals: immunohistochemical analysis of the expression of TGF- β and VEGF

OBJECTIVE:

During the neonatal and infancy periods, some chronic liver diseases may lead to progressive hepatic fibrosis, which is a condition that can ultimately result in the loss of organ function and severe portal hypertension necessitating hepatic transplantation. In a previous report, pharmacological interventions were demonstrated to modulate hepatic fibrosis induced by bile duct ligation in young rats. The administration of pentoxifylline or prednisolone, or the combination of both, resulted in reduced fibrogenesis in portal spaces. The objectives of the present study were to evaluate the expression of transforming growth factor β and vascular endothelial growth factor after bile duct ligation in young rats and to assess the effect of those same drugs on cytokine expression.

METHODS:

In this experimental study, 80 young rats (21 or 22 days old) were submitted either to laparotomy and common bile duct ligation or to sham surgery. The animals were allocated into four groups according to surgical procedure, and the following treatments were administered: (1) common bile duct ligation + distilled water, (2) sham surgery + distilled water, (3) common bile duct ligation + pentoxifylline, or (4) common bile duct ligation + prednisolone. After 30 days, a hepatic fragment was collected from each animal for immunohistochemical analysis using monoclonal antibodies against transforming growth factor β and vascular endothelial growth factor. Digital morphometric and statistical analyses were performed.

RESULTS:

The administration of pentoxifylline reduced the transforming growth factor β-marked area and the amount of transforming growth factor β expressed in liver tissue. This effect was not observed after the administration of prednisolone. There was a significant reduction in vascular endothelial growth factor expression after the administration of either drug compared with the non-treatment group.

CONCLUSIONS:

The administration of pentoxifylline to cholestatic young rats resulted in the diminished expression of transforming growth factor β and vascular endothelial growth factor in liver tissue. The administration of steroids resulted in the diminished expression of vascular endothelial growth factor only. These pathways may be involved in hepatic fibrogenesis in young rats submitted to bile duct ligation and exposed to pentoxifylline or prednisolone.     

Gadolinium chloride suppresses hepatic oval cell proliferation in rats with biliary obstruction.

Liver injury due to bile duct ligation (BDL) is histologically characterized by cholestasis, bile ductular proliferation, hepatocellular damage, portal fibrosis, and ultimately biliary cirrhosis. Stem cells within the liver may act as progenitor cells for small epithelial cells termed oval cells that can differentiate into bile duct cells or hepatocytes, whereas myofibroblasts are the principal source of collagen production in fibrosis. The aims of this study were to determine 1) whether BDL induces oval cell proliferation and 2) whether blockade of Kupffer cells affects oval cell proliferation, bile duct proliferation, and myofibroblast transformation in experimental biliary obstruction. Male Sprague-Dawley rats were divided into two groups to receive either a single dose of gadolinium chloride (a selective Kupffer cell blocking agent) or vehicle. One day later, the gadolinium- and vehicle-treated groups were further subdivided to receive either BDL or sham operation. The rats were sacrificed on day 7 postoperatively. Serum was collected for measurement of aspartate aminotransferase, gamma-glutamyl transpeptidase, and bilirubin levels. Liver tissue was taken for evaluation of fibrosis, bile ductular cells, oval cells, and myofibroblasts. BDL resulted in elevated aspartate aminotransferase, gamma-glutamyl transpeptidase, and bilirubin in serum, and gadolinium pretreatment did not modify these effects. BDL induced marked oval cell proliferation, which was completely prevented by gadolinium pretreatment. Gadolinium did not affect the induction of bile duct expansion or myofibroblasts after BDL. We conclude that experimental biliary obstruction induces oval cell proliferation, which can be prevented by gadolinium pretreatment. This suggests that bile ductular proliferation and myofibroblast transformation are not mediated by Kupffer cells and that ductular proliferation can proceed in the absence of oval cells. Alternatively, gadolinium may directly affect oval cell proliferation after BDL.     

Beneficial Effect of Caffeic Acid Phenethyl Ester (CAPE) on Hepatocyte Damage Induced by Bile Duct Ligation: An Electron Microscopic Examination

Recently the authors have reported the potent beneficial effect of caffeic acid phenethyl ester (CAPE) on cholestatic oxidative liver injury induced by acute bile ligation in Swiss albino rats. Herein, they report the ultrastructural hepatocellular alterations induced by acute bile duct ligation and the effect of CAPE administration on these alterations. Bile duct ligation resulted in many degenerative changes, such as vacuolization, mitochondrial degeneration, endoplasmic reticulum dilatation, and lysosome accumulation within the cytoplasm of hepatocytes. Mitochondrial degeneration was also observed within the cytoplasm of the cells of biliary ductular epithelium. CAPE potentially protected the hepatocytes from the cholestasis-induced cellular injury.     

Beneficial Effects of Glycocholic Acid (GCA) on Gut Mucosal Damage in Bile Duct Ligated Rats

In order to investigate the effect of bile acids on gastrointestinal inflammations, bile duct ligated rats (BDL) were treated with GCA (25 mM/ml, oral or colonic) or saline 1 h before ethanol challenge and twice daily for 3 days in the ileitis group, while GCA was given twice daily for 3 days in the colitis group. BDL reduced the macroscopic and microscopic damage scores in the ileitis group compared to sham operated group, while it had no significant effect on ulcer or colitis groups. However, GCA given in BDL group reduced the ulcer index and microscopic damage in colitis group compared to saline-treated groups, but had no effect in ileitis group. Both BDL and GCA administration in BDL group reduced ileitis- or colitis-induced elevations in MPO levels. GCA administration in BDL group inhibited gastric acid output and volume. Our results suggest that oral or colonic administration of primary bile acids may be useful for the treatment of gastrointestinal inflammations.     

Antihyperglycaemic and Antioxidant Effects of Adenia Lobata engl. (Passifloraceae) in Streptozotocin-Induced Diabetic Rats

The antihyperglycaemic and antioxidant activities of a Ghanaian medicinal plant namely Adenia lobata Engl (Passifloraceae), used to treat diabetes mellitus in traditional medicine, was investigated. The dried stem powder of A. lobata was successively extracted by Soxhlet with petroleum ether and 70% ethanol to obtain the crude petroleum ether (PEAL: yield =1.1w/w %) and ethanol (EEAL: yield = 5.4 w/w %) extracts. The extracts were assessed for their antihyperglycaemic and antioxidant activities. The antihyperglycaemic activity of PEAL and EEAL were determined in streptozotocin-induced diabetic rats (70 mg/kg body weight). Five groups of diabetic rats were given 150, 300 and 600 mg/kg body weight of PEAL and EEAL orally once daily for 20 days. Glibenclamide (5 mg/kg body weight) was used as positive control while distilled water (5 ml) acted as the normal diabetic control. The blood glucose levels were monitored initially for 6 hours and subsequently over 24 days. Both extracts exhibited statistically significant (p< 0.001) antihyperglycaemic activity throughout the study period, with EEAL showing the greatest activity. The antioxidant properties of the petroleum ether and ethanol extracts of A. lobata (PEAL and EEAL) were evaluated using five assays; total phenolic content, total antioxidant capacity, reducing power, DPPH scavenging effect and lipid peroxidation activity. In all these assays, the antioxidant properties increased with increasing concentration of the extracts.     

Evaluation of the Toxicological Profile of the Leaves and Young Twigs of Caesalpinia Bonduc (Linn) Roxb

Acute and sub-acute toxicological effects of ethanolic extract of the leaves and young twigs of Caesalpinia bonduc were carried out on albino rats. Single extract doses from 2000 to 5000 mg/kg body weight were administered orally and monitored for 14 days in acute study, while extract doses from 200 to 1600 mg/kg body weight were orally administered daily for 28 days in sub-acute study and recovery was assessed 14 days after dosing. Biochemical, haematological and histopathological examinations were carried out. There was no mortality in the experimental animals in all acute treatment doses. However, there were significant alterations in the biomarkers and induced cellular damage to the liver in all acute treatment doses. In the sub-acute toxicity treatment, the assessed biomarkers were unaffected at extract dose of 200 mg/kg body weight compared to control, while significant changes were observed in rats administered with extract doses of 400 mg/kg body weight and above. No significant difference was observed between the tested groups and the recovery groups in the sub-acute toxicity study. In conclusion, the ethanolic extract of C. bonduc could be toxic to selected organs of the rat body in acute and sub-acute treatments.     

Hepatoprotective Properties of Aqueous Leaf Extract of Persea Americana,Mill (Lauraceae) ‘Avocado’ Against CCL4-Induced Damage in Rats

Background

Natural products from plants have received considerable attention in recent years due to their diverse pharmacological properties, including antioxidants and hepatoprotective activities. The protective effects of aqueous extract of Persea americana (AEPA) against carbon tetrachloride (CCl₄)-induced hepatotoxicity in male albino rats was investigated.

Materials and Methods

Liver damage was induced in rats by administering a 1:1 (v/v) mixture of CCl₄ and olive oil [3 ml/kg, subcutaneously (sc)] after pre-treatment for 7 days with AEPA. Hepatoprotective effects of AEPA was evaluated by estimating the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and levels of total bilirubin (TBL). The effects of AEPA on biomarkers of oxidative damage (lipid peroxidation) and antioxidant enzymes namely, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were measured in liver post mitochondrial fraction.

Results

AEPA and Reducdyn® showed significant (p<0.05) hepatoprotective activity by decreasing the activities of ALT, AST, ALP and reducing the levels of TBL. The activities of antioxidant enzymes, levels of malondialdehyde and protein carbonyls were also decreased dose-dependently in the AEPA-treated rats. Pre-treatment with AEPA also decreased the serum levels of glutathione significantly.

Conclusion

These data revealed that AEPA possesses significant hepatoprotective effects against CCl₄-induced toxicity attributable to its constituent phytochemicals. The mechanism of hepatoprotection seems to be through modulation of antioxidant enzyme system.     

Splenectomy ameliorates portal pressure and anemia in animal models of cirrhotic and non-cirrhotic portal hypertension

PurposePortal hypertension (PH)-associated splenomegaly is caused by portal venous congestion and splanchnic hyperemia. This can trigger hypersplenism, which favors the development of cytopenia. We investigated the time-dependent impact of splenectomy on portal pressure and blood cell counts in animal models of non-cirrhotic and cirrhotic PH.Materials and methodsNinety-six rats underwent either partial portal vein ligation (PPVL), bile duct ligation (BDL), or sham operation (SO), with subgroups undergoing additional splenectomy. Portal pressure, mean arterial pressure, heart rate, blood cell counts and hemoglobin concentrations were evaluated throughout 5 weeks following surgery.ResultsFollowing PPVL or BDL surgery, the animals presented a progressive rise in portal pressure, paralleled by decreased mean arterial pressure and accelerated heart rate. Splenectomy curbed the development of PH in both models (PPVL: 16.25 vs. 17.93 ?mmHg, p ?= ?0.083; BDL: 13.55 vs. 15.23 ?mmHg, p ?= ?0.028), increased mean arterial pressure (PPVL: +7%; BDL: +9%), and reduced heart rate (PPVL: ?10%; BDL: ?13%). Accordingly, splenectomized rats had lower von Willebrand factor plasma levels (PPVL: ?22%; BDL: ?25%). Splenectomy resulted in higher hemoglobin levels in PPVL (14.15 vs. 13.08 ?g/dL, p ?< ?0.001) and BDL (13.20 vs. 12.39 ?g/dL, p ?= ?0.097) animals, and significantly increased mean corpuscular hemoglobin concentrations (PPVL: +9%; BDL: +15%). Thrombocytopenia only developed in the PPVL model and was alleviated in the splenectomized subgroup. Conversely, BDL rats presented with thrombocytosis, which was not affected by splenectomy.ConclusionsSplenectomy improves both cirrhotic and non-cirrhotic PH, and ameliorates the hyperdynamic circulation. Hypersplenism related anemia and thrombocytopenia were only significantly improved in the non-cirrhotic PH model.     

Evidence for intestinal oxidative stress in obstructive jaundice‐induced gut barrier dysfunction in rats

Aim: An important factor that promotes bacterial and endotoxin translocation in obstructive jaundice is intestinal injury that causes increased permeability. However, little is known of the submicroscopic biochemical events leading to defects of the intestinal barrier. This study was undertaken to investigate the effect of experimental obstructive jaundice on intestinal lipid peroxidation, protein oxidation and thiol redox state. Methods: Rats were randomly divided into controls, sham operated and bile duct ligated (BDL). After 10 days, intestinal barrier function was assessed by measuring endotoxin in portal and aortic blood. Tissue samples from the terminal ileum were examined histologically and morphometrically, while other samples were homogenized for the determination of lipid peroxidation, protein oxidation and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non‐protein mixed disulphides (NPSSR), protein thiols (PSH) and protein disulphides (PSSP)]. Results: Obstructive jaundice compromised intestinal barrier function leading to significant portal and systemic endotoxaemia. The intestinal mucosa in jaundiced rats was atrophic with significantly decreased villous density and total mucosal thickness. Determination of biochemical parameters of oxidative stress in the intestine showed increased lipid peroxidation and protein oxidation in BDL‐rats. Thiol redox state revealed the presence of intestinal oxidative stress in jaundiced rats, indicated by a decrease in GSH and increased GSSG, NPSSR and PSSP. Conclusions: This study shows that experimental obstructive jaundice induces intestinal oxidative stress, which may be a key factor contributing to intestinal injury and leading to endotoxin translocation.     

The effects of the hydroalcohol extract of Rosa canina L. fruit on ischemic acute renal failure in Wistar rats

This research evaluated the possible therapeutic potential of Rosa canina as a preventive agent in ischmia/reperfusiom induced acute renal failure in rats. There were three groups (n?=?10), in which rats received orally 7?days before induction of ischemia, hydroalcoholic extract of R. canina (500?mg/kg) in R. canina?+?ischmia/reperfusiom (I/R) group and distilled water in I/R group. In sham group, the renal arteries were not occluded and distilled was administered orally 7?days before surgery. Renal ischemia was induced by both renal arteries occlusion for 45?min followed by 24?h of reperfusion. Blood samples were collected for biochemical analysis, and finally both kidneys were preserved for future histological examination. R. canina treatment reduced total renal histopathological score as well plasma creatinine and blood urea nitrogen levels in R. canina?+?I/R group in comparison to I/R group. According to these results, R. canina can be useful as a preventive agent against renal damages induced by ischemia/reperfusion injury in rat.     

Protective effect of curcumin against experimentally induced aflatoxicosis on the renal cortex of adult male albino rats: a histological and immunohisochemical study

Background: Aflatoxin contamination of foods is a worldwide problem. Chronic aflatoxin exposure is associated with kidney damage. Curcumin is a herbal agent, used in medicine with a wide range of beneficial therapeutic effects. Objective: to evaluate the effect of curcumin against experimentally induced aflatoxicosis on the renal cortex of adult male albino rats. Materials and methods: Forty adult male rats were included and they were divided equally into 4 groups (10 rats each): Group I (control group), group II (Curcumin group): The rats received curcumin (200 mg/kg b.w.) orally by gastric tube for 5 days/week, group III (Aflatoxin B1 group): The rats received aflatoxin B1 (250 μg/kg b.w./day) orally by gastric tube 5 days/week for 4 weeks, group IV (Aflatoxin B1 and Curcumin group): The rats received aflatoxin and curcumin orally by gastric tube 5 days/week for 4 weeks. Kidney specimens were prepared and sections were stained with hematoxylin and eosin, Masson’s trichrome, Periodic acid Schiff, immunohistochemical detection of desmin and Bcl2. Results: The tubules of group III showed degenerative and necrotic changes with disruption of basal lamina. There was a significant decrease Bcl2 expression in the tubules, but the glomeruli showed an enlargement with dilation of their capillaries lumina in some areas, while the other areas showed glomerular atrophy with obliteration of their capillaries lumina. There was a significant increase in desmin expression in the glomerular cells. The interstitium showed hemorrhage and cellular infiltration. Group IV showed improvement of the histological and immunohistochemical changes described before. Conclusion: Aflatoxin B1 has deleterious effects of on the histological structure of the rat’s renal cortex and curcumin minimized these effects as it has antioxidant, anti-inflammatory and antiapoptotic activities. We advise eating nutritious diets that contain sufficient amounts of curcumin and regulation must implement to avoid the presence of aflatoxins in high concentrations in human food.     

Protective effects of melatonin against spinal cord injury induced oxidative damage in rat kidney: A morphological and biochemical study

Spinal cord injury (SCI) induced oxidative stress affects multiple organ systems including the kidney. We studied the possible protective effects of melatonin on SCI-induced oxidative damage in renal tissues of rats. Wistar albino rats (n = 24) were exposed to SCI and divided into vehicle- or melatonin-treated SCI groups. Melatonin was administred intraperitoneally at a dose of 10 mg/kg for seven days. Renal tissues were investigated by light and electron microscopy. Furthermore, tissue malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and superoxide dismutase (SOD) activities were also determined. In the vehicle-treated SCI group, the renal histology was disturbed compared to controls, whereas the melatonin-treated SCI group showed significantly reduced degeneration of renal tissue as seen by both light and electron microscopy. MDA levels, MPO and SOD activities were increased and GSH levels were decreased in the vehicle-treated SCI group compared to controls. On the other hand, decreased MDA levels and MPO activities and increased GSH levels were observed in the melatonin-treated SCI group compared to vehicle-treated SCI group. These results showed that experimentally induced SCI caused oxidative stress in the rat kidney, whereas melatonin treatment reduced oxidative stress, suggesting that it may be used as a complementary therapy of renal problems occurring following SCI.     

Ingestion of low concentrations of sucrose or hydrochloric acid solutions accelerates mortality in rats with cholestatic liver disease

Mortality rates were monitored in bile duct ligated (BDL) rats which were consuming flavor solutions in addition to water and chow. Following ligation of the common bile duct, animals were offered a single concentration of a flavor solution (200 mM NaCl; 400 mM sucrose; 100 mM urea; 5 mM HCl) in addition to water. During three weeks postligation, mortality rates were compared between groups of ligated animals consuming either one of the taste solutions or consuming only water. Within the first five days postligation, mortality was 70% in ligated animals drinking HCl and 50% in animals consuming sucrose, compared to 30% for urea, 10% for sodium chloride and 0% in animals drinking only water. Total mortality of ligated rats consuming HCl or sucrose solutions was significantly increased compared to animals consuming only water. The results suggest that consumption of low concentrations of sucrose or HCl solutions during the initial stages of liver disease in BDL rats may drastically accelerate their mortality rate.     

Effect of aqueous extract of Cochlospermum planchonii rhizome on some kidney and liver functional indicies of albino rats

Aqueous extract of Cochlospermum planchonii Hook. Ef. x Planch rhizome was investigated for its toxic effects in albino rats using some liver and kidney functional indices as 'markers'. Thirty six albino rats weighing 200.08 ± 10.21 were randomly assinged into six groups (A-F) of six animals each. Animals in groups A-E were orally administered on daily basis with 1 ml of the extract corresponding to 50 mg/kg body weight of the extract for 1, 3, 5, 10 and 15 days while those in the control group received orally 1 ml of distilled water. Rats in all the groups were sacrificed 24 hours after the completion of their respective doses. The extract significantly (P<0.05) decreased alkaline phosphatase (ALP) activities in the liver leading to 80.95% loss by the end of the experimental period. While there was no consistent pattern in the kidney ALP activity and serum bilirubin level, the serum enzyme compared well (P>0.05) with the control value. There was no effect (P>0.05) on the acid phosphatase activity of the tissues and serum of the animals. The extract also reduced the urea, albumin and creatinine content in the serum of the animals. The alterations in the biochemical parameters by the aqueous extract of Cochlospermum planchoni may have consequential effects on the normal functioning of the liver and kidney of the animals. Therefore, the 50 mg/kg body weight of the aqueous extract of Cochlospermum planchoni rhizome may not be completley safe as an oral remedy.     

血必净注射液对急性梗阻性黄疸大鼠心肌损伤的保护作用

目的：观察血必净注射液对急性梗阻性黄疸大鼠心肌损伤的保护作用。方法：采用结扎SD大鼠胆总管的方法制作急性梗阻性黄疽动物模型。将54只SD大鼠随机均分为胆总管结扎（BDL）组、胆总管结扎血必净治疗组（XBJ）、假手术组（SO）3组。XBJ组在胆总管结扎后48h开始尾静脉注射血必净注射液,BDL组和SO组同样方法注射等量生理盐水。分别于给药后第3、7、14天各取6只大鼠采样,观察血清胆红素（TBIL）、肌酸激酶同工酶（CK—MB）、内毒素（ET）含量,心肌组织丙二醛（MDA）和超氧化物歧化酶（SOD）含量,以及光镜下观察心肌病理变化。结果：急性胆道梗阻后,血清TBIL、CK—MB、ET水平及心肌组织MDA含量随梗阻时间延长逐渐增高,心肌组织SOD含量减少。XBJ组与同时相BDL组比较,血清TBIL、CK—MB、ET水平及心肌组织MDA含量减少,心肌组织SOD含量增高。光镜下可见随胆道梗阻时间延长,心肌损伤加重,XBJ组与同时相BDL组比较,心肌损伤减轻。结论：血必净注射液对急性胆道梗阻所致心肌损伤有保护作用,作用机制可能与其抗内毒素血症、TNF—α作用及对抗氧自由基有关。     

Hepatocyte growth factor attenuates liver fibrosis induced by bile duct ligation

Hepatic fibrosis is a common outcome of a variety of chronic liver diseases. Here we evaluated the therapeutic efficacy of hepatocyte growth factor (HGF) on liver fibrosis induced by bile duct ligation (BDL) and investigated potential mechanisms. Mice underwent BDL, followed by intravenous injections of naked HGF expression plasmid or control vector. HGF gene therapy markedly ameliorated hepatic fibrotic lesions, as demonstrated by reduced alpha-smooth muscle actin (alphaSMA) expression, attenuated deposition of type I and type III collagen, and normalized total hydroxyproline content. HGF also suppressed transforming growth factor-beta1 (TGF-beta1) expression. Interestingly, colocalization of alphaSMA and cytokeratin-19 in bile duct epithelium was observed, suggesting the possibility of biliary epithelial to myofibroblast transition after BDL. Cells that were still positive for cytokeratin-19 but actively producing type I collagen were found in the biliary epithelia and periductal region. Laminin staining revealed an impaired basement membrane of the bile duct epithelium in diseased liver. These lesions were largely prevented by HGF administration. In vitro, treatment of human biliary epithelial cells with TGF-beta1 induced alphaSMA and fibronectin expression and suppressed cytokeratin-19. HGF abolished the phenotypic conversion of biliary epithelial cells induced by TGF-beta1. These results suggest that HGF ameliorates hepatic biliary fibrosis in part by blocking bile duct epithelial to mesenchymal transition.