Bile Secretion In Rats Research Articles

CHOLERETIC EFFECT OF THE COMPLEX PLANT SUPPLEMENT IN EXPERIMENTAL LIVER DAMAGE

Relevance. The search for supplements with choleretic activity is of great interest due to their detoxicant properties and possible hepatoprotective ef-fect. The aim of our study was to evaluate choleretic effect of the complex plant supplement comprised of Hypecoum erectum L.; Hedysarum dahuri-cum Turcz. ex B.Fedtsch.; Glycyrrhiza uralensis Fisch. ex DC.; Calendula officinalis L.; Scutellaria baicalensis Georgi. dry extracts. Material and methods. The research was conducted on an animal model of acute liver damage induced by CCl4 in 84 albino Wistar rats. The studied complex plant supplement was researched in doses of 100mg/kg, 200 mg/kg and 300 mg/kg in the course of 14 days starting from the 2nd day of the experiment. Choleretic properties were evaluated by both the speed of bile secretion (mg/min) per 100 g of animal weight and the total amount of bile secreted during four hours of observation. Results. It has been established that the use of the dry extract in tetrachloromethane hepatitis in white rats has a choleretic effect characterized by an increase in the rate of bile secretion, an increase in the amount of discharged bile and the growing concentration of bile acids.

Pharmacological study of original extracts of corn silk

Aim: the aim of the research is a pharmacological study of the original extracts of corn silk. Materials and methods. The object of the study were 4 original extracts of corn silk, obtained by extraction with water and ethanol of different concentrations, namely: aqueous extract of corn silk (ACSE), extract of corn silk, extracted with ethanol 30 % (ECSE 30 %) , extract of corn silk, extracted with ethanol 50 % (ЕCSЕ 50 %), extract of corn silk, extracted with ethanol 70 % (ЕCSЕ 70 %). A screening study of the antioxidant properties of corn silk extracts was carried out in vitro using models of spontaneous and ascorbate-induced lipid peroxidation (LPO) in rat liver homogenate. Results. As can be seen from the given data, ECSE 50 % at a dose of 20 mg/kg showed a pronounced protective effect on the hepatotoxicity of TСM. Its use led to a probable restoration of the bile-forming function of the liver against the background of tetrachloromethane hepatitis: in response to an increase in the cholesterol content (by 43 %, p<0.05), the content of bile acids increased 2 times (p<0.05), as a result of which cholate -cholesterol ratio approached the level of indicators of intact animals, the rate of bile secretion normalized. Based on the analysis of the results of the study, it can be concluded, that in terms of bile-forming and choleretic activity on the tetrachloromethane hepatitis model, ECSE 50 % was not inferior to silibor and superior to quercetin (р<0.05). Conclusions. Biologically active substances of corn silk affect not only the diffusion and filtration processes of the liver parenchyma, but also the biosynthesis and transport of its organic components, that is, they affect the bile-forming function

Metformin impairs bile acid homeostasis in ethinylestradiol-induced cholestasis in mice

Metformin, an oral antidiabetic drug, recently demonstrated a reducing effect on bile acids (BA) plasma concentrations in one patient with intrahepatic cholestasis of pregnancy (ICP) by unknown mechanism. Therefore, the aim of the present study was to examine the effect of metformin on BA homeostasis and related molecular pathways in the liver and intestine using a mouse model of ICP. The cholestasis was induced in female C57BL/6 mice by repeated administration of ethinylestradiol (10 mg/kg BW s.c.) and/or metformin (150 mg/kg BW orally) over 5 consecutive days with subsequent bile collection and molecular analysis of samples. We demonstrated that metformin significantly increased the rate of bile secretion in control mice. This increase was BA dependent and was produced both by increased liver BA synthesis via induced cholesterol 7α-hydroxylase (Cyp7a1) and by increased BA reabsorption in the ileum via induction of the apical sodium-dependent BA transporter (Asbt). In contrast, metformin further worsened ethinylestradiol-induced impairment of bile secretion. This reduction was also BA dependent and corresponded with significant downregulation of Bsep, and Ntcp, major excretory and uptake transporters for BA in hepatocytes, respectively. The plasma concentrations of BA were consequently significantly increased in the metformin-treated mice. Altogether, our data indicate positive stimulation of bile secretion by metformin in the intact liver, but this drug also induces serious impairment of BA biliary secretion, with a marked increase in plasma concentrations in estrogen-induced cholestasis. Our results imply that metformin should be used with caution in situations with hormone-dependent cholestasis, such as ICP.

Compartmental model to estimate bile acid concentration in different clinical manifestation

Objectives: To design a bio-compartmental model of enterohepatic circulation; and to estimate the concentration of bile acid in a different compartment and to understand the various pathological states connected to bile concentration. Methods: The model is based on parameters of volume of bile juice, the mass of bile acid, and the rate of bile secretion in all compartments. The model estimates various clinical manifestations of gallbladder and intestine describing the variable concentration of bile acid based on pathological state and application of mathematical simulation of fractional derivative (MATLAB). Findings: Compatibility of the model results considering pathological data allows us to estimate bile acid concentration in different pathological conditions, thus alters the physiology of enterohepatic circulation. Based on a pathological case the bile acid concentration was estimated and then the fractional derivative was applied to understand the severity of bile-related disorder with the help of mathematical simulation. The graphical results are obtained by applying fractional-order derivative (A Caputo sense) in different pathological cases depicts the varying bile acid concentration in the intestine, liver, and gallbladder comparative to a normal concentration. All findings clearly mentioned in section 4 (Results and Discussion). Novelty/Applications: Mathematical simulation of deposition of bile acid in conjugation with enterohepatic circulation, compartment model helps to understand the pathological disorder and etiology with the clinical symptoms of bile secretion. Keywords: Intestine; Gallbladder; Liver; Enterohepatic circulation; Bile acid concentration; Mathematical modeling.

Pharmacognostic Study of Collection and Study of its Hepatoprotective Activity

Background: The aim of this work is pharmacognostic study of herbal formulation consisting of elecampane rhizomes and roots (Inula helenium L.), fruits of rose (Rosa sp.) and hawthorn (Crataegus sp.), leaves of pepper mint (Mentha piperita L.) and cowberry leaves (Vaccinium vitis-idaea L.), spiny eleuterococcus rhizomes and roots (Eleutherococcus senticosus (Rupr.et Maxim.) Maxim., low cudweed herb (Gnaphalium uliginosum L.s.l.) as well as determination of its hepatoprotective activity. Materials and methods: An electron microscope, HPLC and methods of the State Pharmacopoeia of Russia were used in pharmacognostic study of herbal formulation. The hepatoprotective, antioxidant and choleretic activities of the herbal formulation were studied in vivo model of liver damage induced by tetracycline hydrochloride and 40% ethanol. Results: The content of biologically active substances (BAS) collected: essential oils - at least 0.30%; flavonoids in terms of luteolin - not less than 1.0%; ascorbic acid - not less than 0.5%; tannins - not less than 3.0%; arbutin - at least 0.4%; eleutheroside B - not less than 0.01%.It has been found that the course administration of herbal formulation to white Wistar rats with liver damage eliminates the prooxidant effect of tetracycline and ethanol, reduces the manifestation of cholestasis and increases the rate of bile secretion for 1-3 hours. Conclusion: The herbal formulation has hepatoprotective activity, antioxidant, choleretic effect and stimulates regenerative and antitoxic processes in the liver in rats with a model of combined liver damage induced tetracycline and ethanol. The obtained research results argue the possibility of using herbal formulation for prevention and complex treatment of liver diseases.

Alterations of bile secretion indicators with blunt multiple abdominal injury and underlying ischemia-reperfusion of the limbs

It is known that ischemia-reperfusion has a significant negative impact on combined trauma. It is clear that there is an impression and dysfunction of internal organs against the background of activation of systemic pathological processes, especially those responsible for detoxification processes. However, these processes are little studied in detail, in particular regarding the violation of bile secretion. There is no clear data, and evidence of exactly how ischemia-reperfusion affects liver function in the case of blunt combined trauma to the abdominal organs and how much bile production deteriorates. This is what has become the subject of research.Objective of research: to study dynamic peculiarities of the liver bile secreting function in response to abdominal injury complicated by hypovolemic shock and ischemic-reperfusion syndrome. Materials and methods. 80 mature albino male Wistar rats with the body weight of 190-220 grams kept on standard vivarium forage were used in the experiment. The animals were divided into the control and 3 research groups (containing 8 animals each). Arresting bleeding tourniquet was applied proximally on the lower limbs of rats from the first research group for 120 minutes under thiopental-sodium anesthesia (40 mg/kg-1), which caused development of ischemic-reperfusion syndrome. Closed abdominal injury was simulated by means of delivering two dosed blows in the region of the abdominal cavity in the second research group; hypovolemic shock was simulated by means of cutting the femoral vessels and bloodletting from 20 to 22 % of the circulating blood volume in the group. Injuries from the first two groups were combined in the third group. The control group of animals received anesthesia without formation of any injuries. Bile secreting function of the liver was studied on the basis of identification of the content of total, conjugated/direct and unconjugated/indirect bilirubin in bile, and the volume of bilirubin conjugation degree in bile. The animals of the research groups were removed from the experiment under thiopental-sodium anesthesia by means of the total bloodletting from the heart.Results. A considerable disorder of the bile secreting function of the liver was found in response to simulated injuries: bile secretion rate in the first research group in comparison with the control one achieves minimal values in 3 days and remains on the same level till the seventh day of the post-traumatic period. In the second group the parameter does not change during 1-3 days, though it decreases sharply in seven days. Unidirectional decrease was found in the third group till the seventh day of the experiment.The data obtained are clearly indicative of a negative effect of ischemic-reperfusion syndrome on the bile-forming and bile secreting functions of the liver. Effect of the liver function was found both with isolated action and with multiple injuries of the abdominal organs, when bilateral compromised syndrome is observed. Conclusions: The study proved that the combined blunt trauma of the abdominal organs negatively affects the process of bile formation. Also, in the presence of ischemia-reperfusion of the limb, pathological processes are characterized by a tendency to increase significantly.

The role of mandible injury in the pathogenesis of biochemical and functional liver disorders caused by acute blood loss and two-hour ischemia of limbs, and the efficiency of their correction by carbacetam

Introduction. In the modern world, the prevalence of gunshot wounds has increased significantly. The main cause of death under conditions of gunshot wounds is acute massive blood loss from the extremities. Applying hemostatic tourniquet according to these conditions belongs to the basic aid measures for the wounded on the battlefield. In the structure of gunshot wounds, despite the injury of the extremities, has recently significantly increased the frequency of frontal part injuries of the skull, which remains the least protected part of the body of combatants. There are lesions of the face and facial skeleton in a third of cases with such injuries. However, the effect of mandibular fracture on systemic disorders of acute blood loss complicated by two-hour ischemia-reperfusion of the limb, practically not studied, there are no data on the effectiveness of carbacetam in the case of these conditions.Objective of research: to determine the role of mandibular injury in the pathogenesis of metabolic and functional disorders of the liver caused by acute blood loss and two-hour ischemia of the limb, and to establish the effectiveness of their correction with carbacetam.Materials of the research and their discussion. The experiments were performed on 106 nonlinear male rats weighing 200-220 g. All animals were divided into four groups: control and three experimental. In the first experimental group, the animals were modeled acute blood loss (20% of the circulating blood volume) by intersection of the femoral vein. Ischemia-reperfusion of the limb was simulated on the adjacent thigh by applying a strip of elastic tourniquet "SWAT-T" (USA)10 mm wide for 120 minutes proximately on the left foot. In the second experimental group, animals with acute blood loss and ischemia-reperfusion of the limb, a fracture of mandible from the left was additionally simulated. In the third experimental group, animals with acute blood loss, ischemia-reperfusion of the limb and mandibular fracture for corrective purposes were intraperitoneally administered carbacetam at a dose of 5 mg per kilogram of animal weight.After 1 and 2 hours, as well as after 1, 7 and 14 days in experimental animals were determined indicators of bile-forming, biliary and absorption-excretory function of the liver. Liver homogenate was used to determine the content of thiobarbituric acid reagents (TBA-active LP products), catalase activity, antioxidant-prooxidant index (API) was calculated, and alanine aminotransferase (ALT) activity was determined in serum.Result of the research and their discussion. It is established that modeling of acute blood loss complicated by ischemia-reperfusion of the limb is accompanied by increased intensity of lipid peroxidation processes in the liver, depletion of antioxidant protection with a shift of antioxidant-prooxidant balance towards the strengthening of prooxidant mechanisms. This leads to increased cytolysis and the formation of liver disorder, which is manifested by a slowdown in the formation of total bile acids and the rate of bile secretion with a maximum after 1 day of observation.In the case of these conditions, additional fracture of the mandible contributes to the deterioration of the biochemical and functional state of the liver with a maximum of 1-7 days of observation. By 14 days, the indicators improve, but do not reach the level of control.Thus, a fracture of the mandible exacerbates the severity of systemic disorders caused by acute blood loss and ischemia-reperfusion of the limb. The use of carbacetam under these conditions caused a significant decrease in the content of TBA-active products in the liver, an increase in catalase activity and the value of API after 7-14 days of use. There is also a decrease in the activity of ALT in the blood serum, an increase in the content of total bile acids in the bile, the rate of bile excretion and a decrease in the duration of excretion of bromosulfalein.Conclusions: Additional simulation of mandibular fracture on the background of acute blood loss and ischemia-reperfusion of the limb is accompanied by a deepening of metabolic and functional disorders in the liver. The use of carbacetam for 7-14 days in the reperfusion period for animals with acute blood loss, ischemia-reperfusion of the limb and mandibular fracture, compared with animals without correction, causes a significant decrease in the intensity of lipid peroxidation and cytolysis, less depletion of bile-forming, biliary and absorption -excretory function of the liver.

Вплив екстракту листя лепехи звичайної (Acorus calamus L.) на показники холестазу та жовчовидільну функцію печінки за експериментального гепатиту

Однією з складових уражень печінки є холестатичний синдром, який обумовлено порушенням утворення та відтоку жовчі в кишечник, накопиченням її компонентів у печінці та крові, що проявляється підвищенням активності в крові лужної фосфатази (ЛФ), γ-глутамілтранспептидази (γ-ГТТП), трансаміназ, вмісту холестерину, білірубіну, жовчних кислот тощо. Для корекції синдрому холестазу за алкогольної хвороби та інших уражень печінки часто використовують рослинні та синтетичні засоби з гепатопротекторною й жовчогінною активністю. Мета дослідження – вивчення впливу деалкоголізованого екстракту листя лепехи звичайної (Acorus calamus L.) на процеси жовчоутворення, жовчовиділення та холестазу за умов етанолтетрахлорметанового гепатиту в щурів. Встановлено, що використання деалкоголізованого екстракту листя лепехи звичайної в лікувально-профілактичному режимі за умов гепатиту в щурів, спричиненого введенням тетрахлорметану та етанолу, достовірно зменшує інтенсивність процесу холестазу, покращує жовчосектеторну та жовчоутворювальну функції печінки. Антихолестатичні властивості деалкоголізованого екстракту листя лепехи звичайної підтверджено достовірним зменшенням рівня непрямого та прямого білірубіну, зниженням активності ЛФ і γ-ГТТП. За показниками нормалізації швидкості секреції жовчі, вмісту в жовчі жовчних кислот і холестерину, зменшенням процесів холестазу деалкоголізований екстракт листя лепехи звичайної не поступався препаратам порівняння. Отримані дані свідчать про доцільність подальших поглиблених досліджень екстракту листя лепехи звичайної для створення на її основі ефективних гепатопротекторів.

Morphological rearrangement of large joints of the lower extremities under the conditions of a combination of abdominal and orthopedic trauma complicated by ischemia-reperfusion of the extremity

Introduction. Injuries are among the pressing problems of modern urban society. The structure of injuries is dominated by multiple and combined injuries, which are characterized by significant severity and high mortality and lead to multiple organ dysfunction and insufficiency. In recent years, studies of the functional state of the liver have been widely used as a model for the development of multiple organ dysfunction in conditions of severe experimental trauma.The objective is to determine the nature of disorders of biliary function of the liver in conditions of combined trauma to the abdomen and chest of rats in the early period of traumatic disease and to evaluate the effectiveness of their correction with thiotriazoline.Research materials and their discussion. The experiments were performed on 86 nonlinear white male rats weighing 200-220 g. All animals were divided into five groups i.e. one control group and four experimental ones. Injuries were performed under thiopental-sodium anesthesia. The control group included intact animals that had just been anesthetized. In the first experimental group, the animals were simulated chest trauma. In the second experimental group, a blunt trauma was simulated. In the third experimental group, these injuries were combined. In the fourth experimental group, animals with combined trauma were injected intraperitoneally with thiotriazoline at a dose of 9.1 mg-kg-1. 1, 3 and 7 days after injury under thiopentalone sodium anesthesia in animals, the common bile duct was catheterized and bile was collected for 60 min. It was set the rate of bile excretion. The concentration of total bile acids and conjugated bilirubin was determined in bile, and the rate of their excretion was calculated.Research results and their discussion. Under conditions of isolated trauma of the chest, abdomen and their combination, there is a significant violation of biliary function of the liver, which is primarily manifested by a decrease in the rate of bile secretion and excretion of its main components - cholates and conjugated bilirubin. According to the severity of hepatic dysfunction, they can be divided as follows: isolated chest injury ← isolated abdominal injury ← combined injury. Under conditions of isolated chest trauma, the studied parameters in comparison with the control reach a minimum level of up to 3 days and normalize up to 7 days. After applying an isolated abdominal injury, the rate of bile secretion and the rate of excretion of total bile acids are reduced after 1 day. However, all the studied indicators reach a minimum value after 3 days and remain at the same level until 7 days. After a combined injury, the rates gradually decrease to 7 days and in each subsequent period become significantly lower than in the previous one. The use for the correction of detected disorders of thiotriazoline in the group of animals with combined trauma compared with animals without correction contributed to a significant increase in the rate of bile excretion, excretion of total bile acids and conjugated bilirubin. Although up to 7 days the indicators did not reach the level of the control group, it can be argued that thiotriazoline has a positive effect on biliary function of the liver.Conclusion. Combined trauma to the abdomen and chest contributes to a greater decrease in liver function, compared with isolated lesions. They are based on the suppression of the rate of bile secretion and excretion of total bile acids and conjugated bilirubin. The use of thiotriazoline at a dose of 9.1 mgkg-1 in animals with combined abdominal trauma is accompanied by a significant decrease in biliary dysfunction.

Correction of Toxic Liver Damage with a Multicomponent Herbal Extract in an Animal Experiment

Background: Digestive diseases constitute a significant part in the overall structure of human diseases. Herbal cholagogues are indicated for a treatment of chronic liver, gall bladder, and bile ducts diseases. The aim of the work is to determine the choleretic effect of a new multicomponent plant extract. Materials and Methods: Multicomponent plant extract was obtained from the following types of plant materials: 300 g of immortelle flowers (Helichrysum arenarium L.), 100 g of tansy flowers (Tanacetum vulgare L.), 100 g of rose fruits (Rosa sp.), 100 g of leaves of common nettle (Urtica dioica L.), 50 g of mint leaves (Mentha piperita L.), 50 g of licorice roots (Glycyrrhiza glabra L.). The extract was standardized by the total flavonoid content. It was calculated and expressed in terms of luteolin and isosalipurposide standards (total flavonoids content: not less than 4% and 15% respectively). The animal experiments being done in 80 nonlinear male rats with initial body weight 180-200 g. In order to study a choleretic effect of multicomponent herbal extract, naive rats recieved the single experimental dose of 250 mg/kg. Pharmacotherapeutic activity was studied in white rats with CCl4-induced hepatitis. Results: Studies indicate a pronounced choleretic effect of the studied plant extract, that is comparable with the effect of “Allochol” in intact rats experiments. The course administration of a per os (peroral) multicomponent plant extract in a dose of 250 mg/kg to white non-linear rats with tetrachloromethane liver damage has a choleretic effect: it increases the rate of bile secretion, stimulates the synthesis and secretion of cholates with bile, and also the excretion of cholesterol and bilirubin. Conclusion: The obtained research results argue the feasibility of using a multicomponent plant extract containing biologically active substances of phenolic nature in the prevention and comprehensive treatment of liver diseases.

ВПЛИВ ЕНДОГЕННИХ ПРОСТАНОЇДІВ НА ЖОВЧОСЕКРЕТОРНУ ФУНКЦІЮ У ЩУРІВ РІЗНИХ ВІКОВИХ ГРУП

In acute experiments on different age group of 30 white wild-type rats: juvenile (weight 130–175 g), mature (weight 200–250 g) and old (weight 300 g and more) we were investigated the changes in the volume rate of bile secretion with cyclooxygenase inhibition by acetylsalicylic acid (100 mkg/kg weight of animal) which is a blocker of the prostaglandin synthesis enzyme. We explored the changes of the level of choleresis and bile biochemical components by thin-layer chromatography In vivo. The relative abundances of cholecycle, henodeoxycholic, taurocholic and glycocholic bile acids in the liver of rats were determined by chromatography, with the subsequent densitometry. The biliary acid flow rate was calculated as the sum of the bile acid concentration multiplied by the volume of secreted biliary in one relevant thirty-minute sample. The conjugation coefficients were calculated for each thirty minute sample. Reduction of bile secretion by endogenous prostanoids was shown, because inhibition of prostaglandins synthesis caused the hypercholeresis on 42–112,5 % in different rat age groups, compared to control. Endogenous prostaglandins suppressed the processes of conjugation in old and juvenile age group on 117–189,1 %, in contrast these regulators have no significant effect on bile acids association with glycine and taurine in mature rats. The binding of endogenous prostanoids probably increased the conjugation processes in juvenile rats, whereas in the old experimental group acetylsalicylic acid was significantly reduced by 123 % on average. Analysis of changes in free and conjugated bile acids in the rats of different age groups showed that the ratio of qualitative changes in structure of the liver bile in rats with the cyclooxygenase blockade is mainly due to enhanced synthesis of free bile acids de novo. Therefore, endogenous prostanoids affect in the opposite way. There are have multi-directional impact on bile secretion in different age groups of rat that means ambiguous role of these drugs in liver function regulation at different stages of ontogenesis.

Increased bioavailability of celecoxib under fed versus fasted conditions is determined by postprandial bile secretion as demonstrated in a dynamic gastrointestinal model

The objective of this study was to utilize physiologically relevant dynamic dissolution testing with the TNO intestinal model (TIM-1) in vitro gastrointestinal model to investigate the bioaccessibility of celecoxib. A single 200-mg dose of celecoxib was evaluated under average adult human physiological conditions simulated in the TIM-1 system. The in vitro data were compared with the clinically established pharmacokinetic data. When expressed as a percent of drug that progresses from the duodenum to the jejunum and ileum compartments (bioaccessible sites), the study demonstrated a 2-fold increase in the total bioaccessibility for celecoxib when co-administered with a high-fat meal as opposed to co-administration with a glass of water (fasted conditions). That increase in bioaccessibility was similar to a 1.2 to 1.6-fold increase in systemic exposure in adults and children following co-administration with a high-fat meal when compared to the exposure measured when celecoxib was co-administered with only water. Following that comparison, the flexibility of the TIM-1 system was used to more specifically investigate individual parameters of gastrointestinal conditions, such as the rate of bile secretion (emptying of the bile bladder) that accompanies high-fat meal consumption. We demonstrated that increased bile secretion after co-administration of a high-fat meal played a more important role in the increased celecoxib bioaccessibility than did the food matrix. This indicates that in humans without a bile bladder the exposure of celecoxib administered with food might be as low as under fasted state.

Lysimachia christinae Hance regresses preestablished cholesterol gallstone in mice

Ethnopharmacological relevanceWhole herb of Lysimachia christinae has long been used as a remedy for cholelithiasis extensively in China. This study was aimed to validate the effect of L. christinae on eliminating preestablished cholesterol gallstone (CGS) in model animals. Materials and methodsAcute toxicity of aqueous extract of L. christinae (LCAE) was estimated in male C57BL/6 mice, so was the efficiency of LCAE on preformed CGS induced by lithogenic diet. The effects of LCAE were also examined on bile secretion rate, the lipid profiles of bile and serum, body weight, main visceral organ indexes, and histomorphology of main visceral organs. ResultsSingle dose of LCAE did not lead to death and changes on body weight gain, main visceral organ indexes, histomorphology of main visceral organs, and blood hemogram and biochemical indexes, even at dose of 50g material/kg body weight. Preestablished CGSs were almost entirely eliminated after administration of LCAE for 2wk at high dose or for 4wk at low dose. LCAE promoted bile secretion and lowered cholesterol levels in either cystic bile or hepatic bile. LCAE also decreased serum cholesterol content, especially LDL-C content, tremendously, reduced the levels of serum HDL-C, phospholipid, and triglycerine a little, and lowered body weight and liver index significantly. After medication of LCAE for 8wk , neither visceral indexes nor histomorphology of heart, kidney, and spleen were influenced, but fatty degeneration of liver induced by high fat and high cholesterol diet was reverted. ConclusionL. christinae can be considered as non-toxic. It showed prominent efficiency of eliminating preexisted CGS in mice and indicated a hypolipidaemic effect.

Altered biliary flow rate and bile composition following consumption of ethanolic fruit extract of Dennettia in rats

Background:Dennettia tripetala is a tropical plant with some ethno-medicinal uses; it enhances uterine contraction/involution in pregnant and post-partum women, it is also a mild laxative, with anti-bacteria, antifungal properties etc.,Aims:This study sought to elucidate the impact of D. tripetala fruit extract intake on biliary flow rate and bile composition in rats.Materials and Methods:A total of 18 albino Wistar rats were randomly assigned into three groups of 6 rats each and fed on normal rat chow + drinking water and/or 85 mg/kg, 170 mg/kg body weight of D. tripetala extract for 14 days.Results:The rate of bile secretion in the control, low dose (LD) and high dose (HD) D. tripetala extract treated rats was 4.40 ± 0.24 ml/h, 3.20 ± 0.20 ml/h and 4.60 ± 0.25 ml/h respectively. Showing a significant (P < 0.05) decrease in LD and an increase in HD. Na+ concentration increased significantly (P < 0.01) in the LD extract recipients, but was reduced in the HD. LD of the extract increased K+ significantly (P < 0.001) while HD decreased it (P < 0.05). Both low and HD of the extract reduced Cl– concentration significantly (P < 0.05 and P < 0.001 respectively). HCO3– increased significantly (P < 0.05) in the HD extract recipients. However, total cholesterol, total and conjugated bilirubin concentrations were not significantly altered by D. tripetala fruit extracts.Conclusion:In conclusion, this study showed that LD of D. tripetala may reduce bile flow rate while HD may increase it without altering the saturation of cholesterol and bilirubin.

Increased bile flow rate and altered composition of bile induced by ethanolic leaf extract of Azadirachta indica (neem) in rats

Background: Azadirachta indica (neem) is an ever green tropical plant with ethno-medicinal uses; it is a very potent anti-malaria plant. There is a paucity of the scientific literature on the impact of A. indica on the biliary flow rate and bile composition, considering that alterations in bile composition may lead to gall stone. Aim: This study therefore sought to elucidate the impact of A. indica leaves extract on biliary flow rate and bile composition in rats. Materials And Methods: Eighteen (18) albino Wistar rats were randomly assigned into three groups of six rats each and fed on normal rat chow and/or 150 mg/kg, 300 mg/kg body weight of A. indica extract for 21 days. Results: The rate of bile secretion is in the control, low dose (LD) and high dose (HD) A. indica extract treated rats was 3.0 ± 0.02 ml/h, 5.60 ± 0.46 ml/h and 5.38 ± 0.32 ml/h respectively, showing a significant (P < 0.001) increase in LD and HD compared with control. Na + concentration increased significantly (P < 0.05) in the HD extract recipients compared with control. LDs of the extract increased K + significantly (P < 0.001) compared with control and HD. HDs of the extract increased Cl− concentration significantly (P < 0.05) compared with LD. HCO3− did not alter significantly among these groups. LDs of the extract significantly (P < 0.01) increased total cholesterol, total and unconjugated bilirubin concentrations, HDs reduced it. Conclusion: Hence, A. indica leaves extract increases bile flow rate, LDs of the extract increases cholesterol and bilirubin saturations while HDs reduces it.

Dipeptidyl Peptidase 4-Deficient Rats Have Improved Bile Secretory Function in High Fat Diet-Induced Steatosis

Rodent obesity models have been shown to display impaired bile secretory functions. We have shown that glucagon-like peptide 1 (GLP-1) attenuates hepatic lipogenesis, and in the present study we investigated whether GLP-1 also improves high fat diet-associated cholestatic injury. Wild type (WT) and dipeptidyl peptidase 4-deficient rats (DPP4-) with chronic elevated serum levels of active GLP-1 were fed regular chow and a Western diet for 2months. Primary hepatocytes were used to assess GLP-1 effects on mRNA expression and transcription of genes encoding bile acid synthesis enzymes and transporters. DPP4- exhibited attenuated liver injury as expressed by lower serum AST and ALT after 2months of a Western diet. In addition, DPP4- had better insulin sensitivity, lower serum triglycerides, cholesterol and bile acids. Hepatic expression of cyp7A1, the rate limiting enzyme in conversion of cholesterol into bile acids, was strongly attenuated in DPP4- fed with a Western diet. Moreover, hepatic expression of bile transporter, ABCB11, was increased, facilitating a higher rate of bile secretion. Mechanistically, we showed that GLP-1 directly reduced basal and LXR-induced cyp7A1 mRNA expression and suppressed cyp7A1 transcription in transient transfection assays in primary hepatocytes. However, GLP-1 and its analog exendin 4 also induced mRNA expression of bile acid transporter ABCC3 in primary rat hepatocyte cultures. Our data suggest that GLP-1 analogs may serve as a novel therapeutic drug to alleviate obesity-induced liver injury by reducing bile acid synthesis and improving liver bile secretory function.

Troxerutin protects the isolated perfused rat liver from a possible lipid peroxidation by coumarin

For more than 40 years coumarin has been successfully used in the therapy of chronic venous insufficiency (CVI). The occurrence of liver injuries is rather rare and happens predominantly when doses are administered which are significantly higher than necessary for therapeutical use. Such effects caused by high coumarin concentrations are reproducible in in vivo experiments in mice or rats and HepG2-cells. In order to characterize the mechanism of liver injuries, the isolated perfused rat liver has been chosen as model. Since liver injuries are quite rare, if coumarin is used in co-medication with troxerutin, a possible protective influence of this flavonoid has been investigated. In concentrations higher than 4 mmol/l, coumarin alone is effective in the isolated perfused rat liver. Then the release of the enzymes alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) increases and there is a measurable reduction of perfusion flow, oxygen consumption and rate of bile secretion. Additionally, the concentrations of hepatic adenosine triphosphate (ATP) and oxidized and total glutathione (GSSG/GSH) decrease. In the livers of fasting animals, coumarin doubles the concentration of hepatic malondialdehyde (MDA). This effect cannot be detected if troxerutin is added. In general, troxerutin reduces the concentration of all coumarin-metabolites in the perfusate and bile and changes the ratio of the main metabolites, coumarin: 3-hydroxycoumarin: 7-hydroxycoumarin. An analysis of the metabolic steps also shows that the amount of coumarin eliminated via faeces does not stem from absorbed coumarin, because the amount of orally applied coumarin detectable in the bile is less than 1%. The study demonstrates that troxerutin has hepatoprotective properties and thus protects the liver from a possible lipid peroxidation caused by coumarin. However, it is necessary to point out that these adverse effects caused by coumarin can be detected only in very high concentrations considerably above the regular therapeutical dosage. This allows the conclusion that troxerutin is a beneficial cofactor in coumarin preparations used for the therapy of chronic venous insufficiency.

Stimulatory Influence of Select Spices on Bile Secretion in Rats

Stimulatory Influence of Select Spices on Bile Secretion in Rats

Stimulatory influence of select spices on bile secretion in rats

Spices - cumin, coriander, ajowan, fennel, mint, and garlic, were examined for their influence on bile secretion rate and bile acid content of bile in experimental rats both as a result of continued dietary intake and single oral dose of the test spice. Groups of animals were maintained for 8 weeks on the following spice diets : Cumin (1.25 %), Coriander (2.0 %), Ajowan (0.2 %), Fennel (0.5 %), Mint (1.0 %), and Garlic (0.5%). In a separate set of rats, these test spices were also administered as a single intragastric dose (mg/kg body wt : Cumin, 600; Coriander, 400; Ajowan, 80; Fennel, 200; Mint, 400; and Garlic oil, 0.02. Bile flow rate was significantly enhanced by dietary cumin, ajowan, and garlic. Ajowan had this beneficial effect even with a single oral dose. The biliary solids were higher in the case of dietary cumin, coriander, ajowan, fennel and mint. A pronouncedly higher rate of secretion of bile acids was caused by all the test spices except garlic, compared to control, both in dietary treatment as well as in single oral dosage of the spice. Higher rate of bile acids secretion would probably contribute to the digestive stimulant action of the test spices.

General pharmacological properties of the new proton pump inhibitor (+/-)-5-methoxy-2-[[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulf inyl]- 1H-imidazo[4,5-b]pyridine.

The general pharmacological profiles of a novel proton pump inhibitor, (+/-)-5-methoxy-2-[[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulfi nyl]- 1H-imidazo[4,5-b]pyridine, TU-199) on the central nervous system, cardiorespiratory system, autonomic nervous system, gastrointestinal system and renal functions were investigated. TU-199 had no effects on general signs and behavior in mice. TU-199 (300 mg/kg p.o.) decreased locomotor activity 3 h after administration in mice. TU-199 had no effect on pentobarbital-induced hypnosis, analgesic activity and electroshock-induced convulsion in mice, and on rectal temperature in rats. However, TU-199 (300 mg/kg p.o.) showed slight anticonvulsant activity on pentylenetetrazole-induced convulsion in mice. TU-199 had no effect on respiratory rate, blood pressure, heart rate, femoral blood flow and electrocardiogram in anesthetized dogs. TU-199 (10(4) M) caused the cumulative concentration-response curve obtained with acetylcholine in isolated guinea pig ileum to shift to the right. However, TU-199 showed no effect on contraction of isolated guinea pig ileum and had no effect on intestinal motility in mice, gastric emptying in rats, bile secretion in rats and carbachol-induced salivary secretion in mice. TU-199 had no effect on urinary volume and excretion of electrolytes in rats. These results suggest that TU-199 does not induce serious adverse effects on the central nervous system, cardiorespiratory system, autonomic nervous system, gastrointestinal system and renal functions with the exception of a decrease in spontaneous motor activity with high doses.