Detoxification Function Of Liver Research Articles

Isolation and characterization of a hepatoprotective polysaccharide from Lonicera caerulea L. var. edulis Turcz. ex Herd. fruit against APAP-induced acute liver injury mice

The structure and bioactivities of a novel polysaccharide from Lonicera caerulea L. var. edulis Turcz. ex Herd. fruit (THP-3) were investigated. The crude polysaccharides of Turcz. ex Herd. (THP) were extracted by hot water extraction. After purification, the chemical structure of polysaccharides was identified. Then, a mouse model of acute drug-induced liver injury was constructed using 4-acetamidophenol (APAP) and pretreated with THP. The number-average molecular weight of THP-3 was 48.89 kDa and the mass average molar mass was 97.87 kDa. THP-3 was mainly composed of arabinose (42.54 %), glucose (27.62 %), galacturonic acid and galactose (29.84 %). The main linkage types of THP-3 were 1-linked Araf, 1,4-linked Glcp, and 1,3,6-linked Galp. In addition, after THP treatment, serum Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and γ-glutamyl transpeptidase (γGT) in AILI mice were successfully down-regulated. The results showed that THP could prevent the characteristic morphological changes of hepatic lobular injury and lipid depletion caused by APAP, reduced the level of oxidative damage in mice, increased the expression of APAP-induced hypolipidemia and related inflammatory indicators, and improved the detoxification function of liver. In general, the newly extracted THP polysaccharide has a good liver protection effect and is an ideal natural medicine for the treatment of liver diseases.

Effect of drugs regulating acute immune responses on the liver in septic processes

Objective. To study the effect of drugs regulating acute immune responses on liver in septic processes. Materials and methods. The study was conducted on 39 male white rats weighing 250-400 g. The animals were initiated septic process development by intraperitoneal injection of Klebsiella pneumoniae culture suspension with simultaneous intravenous injection of polyvinylpyrrolidone (PVP) and gadolinium in the volume of 0.6 ml. On the 14th day the animals were removed from the experiment by decapitation under light ether anesthesia, blood and liver were taken for biochemical and histological studies. Results. When analyzing the morphometric parameters of liver preparations, an increase in the number of nuclei and a slight increase in the area of nuclei in three experimental groups was established by 1,2 times (p < 0,05) compared to the control group, which reflects the ongoing processes of hepatocyte regeneration due to possible mechanisms, namely hypertrophy nuclei and proliferation with both PVP and gadolinium in systemic inflammatory response and sepsis. Moreover, the use of PVP and gadolinium led to a decrease in the likelihood of perinuclear edema, protein degeneration and large droplet vacuolization (p < 0,05). When using gadolinium, the lumen diameter of the sinusoids was the largest and amounted to 4,47; 3,22-5,63 µm (p<0,05), and in septic shock it did not differ from the group where PVP was used (p > 0,05). Of the laboratory parameters of surviving individuals, the lowest ALaT level was noted in the gadolinium experimental group – 53,7; 51,8-55,1 U/L (p<0,05), while the lowest urea level was observed when using PVP (5,0; 4,99-5,15 mmol/l) (p < 0,05) as part of a systemic inflammatory response. Conclusion. Gadolinium and PVP have a positive effect on the detoxification function of liver. Moreover, the effect of PVP on the morphology and function of the liver differs at the stages of septic process.

КОГНИТИВНЫЕ РАССТРОЙСТВА, АССОЦИИРОВАННЫЕ С НАРУШЕНИЕМ ДЕТОКСИЦИРУЮЩЕЙ ФУНКЦИИ ПЕЧЕНИ, У БОЛЬНЫХ АЛКОГОЛЬНОЙ ЗАВИСИМОСТЬЮ, НОВЫЕ ПОДХОДЫ В ПЕРСОНАЛИЗИРОВАННОЙ ТЕРАПИИ

Introduction. The disruption of the detoxifying function of the liver, the direct toxic effects of alcohol and its metabolites, as the well as increased permeability of the blood-brain barrier lead to alcohol-induced brain damage. A complication of alcoholic liver disease is progressive cognitive dysfunction. Target. Assessment of impairments in the detoxification function of the liver and cognitive disorders in personalized therapy for patients with alcohol dependence. Materials and methods. The study included 30 men 41.5 years of age (32.3-53.0) with mental and behavioral disorders associated with alcohol use, impaired liver detoxification function, and cognitive disorders. To assess cognitive impairment, the following were used: Hamilton Anxiety Scale, Montreal Cognitive Assessment Scale (MoCA), obsessive-compulsive alcohol craving scale, and short-term and long-term memory assessment. Cognitive functions were examined upon admission and on days 10 and 18 of therapy. Biochemical blood parameters (ALT, AST, alkaline phosphatase, total bilirubin, direct bilirubin, indirect bilirubin, cholesterol, malondialdehyde, reduced glutathione) were studied before and after treatment. Results. Against the background of complex therapy, there was a decrease in craving for alcohol, assessed on the obsessive-compulsive scale from 36 (34-39) to 9 (8-11) points on the 10th day of therapy and 3 (2-5) points at the end of the course of treatment (p=0.0001). Biochemical parameters of the blood have improved significantly. Cognitive abilities assessed on the MoCA scale improved from 23.5 (20.3-26.3) to 27 (25.8-28) points, p=0.0001. Prediction of a favorable outcome of therapy (MoCA score greater than 26 points after a course of treatment) is possible based on initial indicators. AST level less than 112 U/L, ALT less than 120 U/L, direct bilirubin less than 9.8 µmol/L and cholesterol less than 6, 7 mmol/l. The probability of achieving less than 7 points on the obsessive-compulsive scale after 10 days of treatment can be predicted by the level of indirect bilirubin before starting therapy of less than 14.2 µmol/l and the initial score on the Hamilton anxiety scale of less than 20.5 points. Conclusions. Restoring liver detoxification function and improving cognitive potential through the use of drugs that combine neuroprotective and hepatoprotective effects in complex therapy is an effective method of treating patients with alcohol dependence. Prediction of a favorable outcome of therapy is possible based on initial biochemical parameters and assessment on the Hamilton Anxiety Scale.

Significance of the liver arginase activity and nitrogen monoxide in the detoxification processes and development of oxidative stress in rats under alcoholic intoxication of different severity

Modern medicine faces the problem of the steady growth of alcoholic pathology. And as you know, morbidity and mortality with regular consumption of alcoholic beverages is associated with the toxic effects of ethanol on the most important human organs and, first of all, the liver. To date, a sufficient number of facts have accumulated indicating the importance of liver arginase and nitrogen monoxide (NO) in vital processes in health and disease.The aim of the study was to elucidate the significance of liver arginase activity and nitrogen monoxide in the detoxification processes and the development of oxidative stress in rats with chronic ethanol intoxication of different severity.In experiments on rats using modern physiological, biochemical research methods and a pharmacological approach, it was found that liver arginase and nitrogen monoxide participate in changes in liver detoxification function and the development of oxidative stress induced by chronic ethanol intoxication. The direction and severity of changes in arginase activity and liver detoxification function during chronic alcoholism depends on the severity of chronic alcohol intoxication. Under the influence of daily intragastric administration for 60 days, a 30 % aqueous solution of ethanol (3.5 g 92 % ethanol per kg of body weight) in animals under conditions of development of oxidative stress inhibited the activity of liver arginase and detoxification function but and the introduction of a 10 % aqueous solution of ethanol (1.0 g 92 % ethanol per kg of body weight) within 2 months leads to an increase in the activity of liver arginase and detoxification processes. The action in the body of the NO-synthase blocker methyl ester NG-nitro-L-arginine weakens, and the arginase inhibitor Nω-hydroxy-nor-L-arginine contributes to the development of characteristic changes in the processes of detoxification and lipid peroxidation in the liver during chronic alcohol intoxication caused by intragastric the introduction of ethanol at a dose of 3.5 g/kg for 60 days.

THE FUNCTIONAL STATE OF LIVER IN PATIENTS WITH METABOLIC SYNDROME WITH TYPE 2 DIABETES

One of the pathogenetic mechanisms of the development of insulin resistance (IR) in type 2 diabetes mellitus (type 2 DM) is the formation of non-alcoholic fatty liver disease (NAFLD). DM and liver pathology can be considered as interrelated processes. The aim of the study was to evaluate the indicator, secretory and excretory enzymes of blood serum in the development of IR in patients with metabolic syndrome (MS) with type 2 DM. The distribution of patients with MS with type 2 DM was carried out, depending on the presence of non-alcoholic steatohepatitis (NASH): a group of patients with NASH - 36, a group of patients without NASH - 32. The degree of IR was determined by the size of the waist circumference, IR indices: HOMA-IR index and Caro index. The obligatory volume of laboratory researches included: the general clinical analysis of blood and urine, research of fasting blood glucose and postprandial glycemia, glycemic profile of blood by glucose oxidase method by means of the «Exan» device was carried out. Glycated hemoglobin (HbA1c) was determined by chromatographic method using a test system (fully automated analyzer) to determine the content of hemoglobin D-10TM by "Bio-Rad" company (USA). Determination of the activity of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, arginase, cholinesterase was performed by diagnostic kits of the Czech company "Lachema" on a spectrophotometer Sf-46. Alkaline phosphatase activity was determined by Phillips-Diagnostic reagent kits. The concentration of endogenous insulin was determined by DRG reagent kit (USA), by enzyme-linked immunosorbent assay using an analyzer "StatFax - 303. To determine the presence of structural changes in the liver the ultrasound on the device "Elegra" Simens Medicol Systems was used. Wefound that the metabolic prerequisites for the development of NASH of the liver are fasting and postprandial hyperglycemia, hyperinsulinemia. The increase in the degree of glycation of hemoglobin and increase in IR. The results of the study of the degree of hemoglobin glycation showed a reliable increase in the relative content of HbA1c in patients with NASH and MS with type 2 diabetes without NASH - 2.1 and 1.9 times, compared with healthy individuals. A study of the content of endogenous insulin in the blood on an empty stomach revealed reliable hyperinsulinemia - in patients with NASH, the content of endogenous insulin on an empty stomach exceeded the norm by 4.3 times. Increased levels of alanine aminotransferase, sorbitol dehydrogenase, arginase, lactate dehydrogenase, alkaline phosphatase and decreased cholinesterase in patients with MS with NASH detected which display the damage of detoxification and synthetic function of the liver and glycogenization. The connection of IR with the deepening of the phenomena of hepatocyte damage, suppression of the synthetic function of hepatocytes, with markers of nonspecific hepatodepsy, reduction of liver detoxification function, glycolysis processes, predictors of necrosis hepatocytes in NASH on the background of MS with type 2 DM determined.

Significance of the activity of liver arginase and Kupffer cells in the detoxification processes and the thyroid status formation in rats under alcoholic intoxication of different severity

Modern medicine faces the problem of a steady growth of alcoholic pathology. As you know, morbidity and mortality with a regular consumption of alcoholic beverages is associated with the toxic effects of ethanol on the most important human organs and, first of all, on the liver. To date, a sufficient number of facts are accumulated, indicating the importance of liver arginase and Kupffer cells in vital processes in health and disease. The aim of the study was to elucidate the significance of the activity of liver arginase and Kupffer cells in the detoxification processes and the thyroid status formation in rats with chronic ethanol intoxication of different severity. In rat experiments using modern physiological, biochemical research methods and a pharmacological approach, it was found that liver arginase and Kupffer cells participate in changes in the liver detoxification function and the thyroid status formation induced by chronic ethanol intoxication. The activity of liver arginase and Kupffer cells determines the severity of detoxification processes and the thyroid status formation in chronic alcohol intoxication. The direction and severity of changes in the arginase activity and the liver detoxification function during chronic alcoholism depends on the severity of chronic alcohol intoxication. Under the influence of daily intragastric administration for 60 days, a 30 % aqueous solution of ethanol (3.5 g 92 % ethanol per kg of body weight) in animals inhibited the activity of liver arginase and the detoxification function, but the introduction of a 10 % aqueous solution of ethanol (1.0 g 92 % ethanol per kg of body weight) within 2 months leads to an increase in the activity of liver arginase and detoxification processes. Kupffer cells depression by GdCl3 as the action in the body of the NO-synthase inhibitor methyl ester NG-nitro-L-arginine weakens and the arginase inhibitor Nω-hydroxy-nor-L-arginine contributes to the development of characteristic changes in the processes of detoxification and triiodothyronine level in plasma during chronic alcohol intoxication caused by intragastric introduction of ethanol at a dose of 3.5 g/kg for 60 days.

ОБ УЧАСТИИ АРГИНАЗЫ ПЕЧЕНИ В ПРОЦЕССАХ ДЕТОКСИКАЦИИ И РАЗВИТИЯ ОКСИДАТИВНОГО СТРЕССА У КРЫС В УСЛОВИЯХ АЛКОГОЛЬНОЙ ИНТОКСИКАЦИИ РАЗЛИЧНОЙ ТЯЖЕСТИ

Modern medicine faces the problem of the steady growth of alcoholic pathology. And as you know, morbidity and mortality with regular consumption of alcoholic beverages is associated with the toxic effects of ethanol on the most important human organs and, first of all, the liver. To date, a sufficient number of facts have accumulated indicating the importance of liver arginase in vital processes in health and disease. The aim of the study was to elucidate the significance of liver arginase in the detoxification processes and the development of oxidative stress in rats with chronic ethanol intoxication of different severity. In experiments on rats using modern physiological, biochemical research methods and a pharmacological approach, it was found that liver arginase participate in changes in liver detoxification function and the development of oxidative stress induced by chronic ethanol intoxication. The direction and severity of changes in arginase activity and liver detoxification function during chronic alcoholism depends on the severity of chronic alcohol intoxication. Under the influence of daily intragastric administration for 60 days, a 30% aqueous solution of ethanol (3.5 g 92% ethanol per kg of body weight) in animals under conditions of development of oxidative stress inhibited the activity of arginase and detoxification function of the liver, and the introduction of 10% aqueous solution of ethanol (1.0 g 92% ethanol per kg of body weight) for 2 months leads to an increase in the activity of liver arginase and detoxification processes. The action in the body of the arginase inhibitor Nω-hydroxy-nor-L-arginine contributes to the development of characteristic changes in the processes of detoxification and lipid peroxidation in the liver during chronic alcohol intoxication caused by intragastric the introduction of ethanol at a dose of 3.5 g / kg for 60 days.

Cortical Visual Impairment as a Manifestation of Hepatic Encephalopathy in a Young Child: A Case Report

Cortical visual impairment (CVI) is an extremely rare manifestation of hepatic encephalopathy (HE), which refers to neuropsychiatric abnormalities as a result of impaired detoxification function of liver. A 16-month-old female Syrian refugee who developed jaundice 4 weeks before referral to our hospital was diagnosed with hepatitis A based on her clinical presentation at a local facility. Overtime, her jaundice worsened, her lower limbs became edematous, and the family noticed sleep disturbances and irritability. On admission to a local hospital, she was deeply jaundiced and irritable, but showed no stigmata of chronic liver dysfunction. During hospitalization, the patient lost the ability to track objects and eventually her sight. However, the results of fundoscopic and neurological examinations were normal, except for a fine tremor. Her laboratory workup showed elevated liver enzymes and ammonia, and a prolongation of prothrombin time. Brain imaging revealed an abnormal signal intensity which is suggestive of metabolic etiology. The patient was diagnosed with CVI secondary to HE and transferred to the pediatric intensive care unit. After a few days of HE management, ammonia levels dropped and vision recovered. In conclusion, CVI may indicate HE in children.

Interaction of liver arginase and L-arginine-NO system in the processes of detoxification, lipid peroxidation and the formation of the thyroid status in rats with chronic ethanol intoxication

A sufficient number of facts testifying the importance of liver arginase and nitrogen monoxide in the life processes in the normal and pathological conditions have been accumulated to date. The aim of the study was to determine the significance of the relationship and interaction of liver arginase and L-arginine-NO system in the processes of detoxification, lipid peroxidation and the formation of the thyroid status in rats with chronic ethanol intoxication. In rat experiments using the modern physiological, biochemical research methods and a pharmacological approach, it was found that chronic ethanol intoxication leads to a decrease in the liver arginase activity and the triiodothyronine concentration. At the same time, the increase in the level of “average molecules”, NO3 – /NO2 –, the content of lipid peroxidation products in the plasma, as well as the increase in the blood toxicity degree, the activity of alanine amino transferase, aspartate amino transferase and the narcotic sleep duration were observed. Hyperthyroid rats demonstrated the increased liver arginase activity, the processes of detoxification, lipid peroxidation and body temperature while rats with the experimental hypothyroidism showed the opposite results. The liver arginase depression caused by the injection of Nω-hydroxy-nor-L-arginine (Nor-NOHA), or L-valine into the body prevents the body temperature increase and the development of characteristic changes in the detoxification and lipid peroxidation processes acted upon by exogenous triiodothyronine. Under the conditions of the liver arginase inhibition by Nor-NOHA or L-valine, the ethanol action is accompanied by a more significant inhibition of the liver detoxification function and an increase of NO3 – /NO2 – levels in blood plasma. The preliminary injection of an NG-nitro-L-arginine methyl ester inhibitor of NO-synthase into the animal’s body weakensthe toxic ethanol effect on the liver, as well asthe development of characteristic changes in the liver arginase activity, in the processes of detoxification and lipid peroxidation in rats with chronic ethanol intoxication. Apparently, the activity of liver arginase and L-arginine-NO system determines the severity of detoxification, lipid peroxidation processes and the formation of the thyroid status in the conditions of chronic alcoholization, which is important in the ethanol intoxication pathogenesis.

A Look into Liver Mitochondrial Dysfunction as a Hallmark in Progression of Brain Energy Crisis and Development of Neurologic Symptoms in Hepatic Encephalopathy.

Background: The relationship between liver disease and neuropathology in hepatic encephalopathy is well known, but the genesis of encephalopathy in liver failure is yet to be elucidated. Conceptually, the main cause of hepatic encephalopathy is the accumulation of brain ammonia due to impaired liver detoxification function or occurrence of portosystemic shunt. Yet, as well as taking up toxic ammonia, the liver also produces vital metabolites that ensure normal cerebral function. Given this, for insight into how perturbations in the metabolic capacity of the liver may be related to brain pathology, it is crucial to understand the extent of ammonia-related changes in the hepatic metabolism that provides respiratory fuel for the brain, a deficiency of which can give rise to encephalopathy. Methods: Hepatic encephalopathy was induced in starved rats by injection of ammonium acetate. Ammonia-induced toxicity was evaluated by plasma and freeze-clamped liver and brain energy metabolites, and mitochondrial, cytoplasmic, and microsomal gluconeogenic enzymes, including mitochondrial ketogenic enzymes. Parameters of oxidative phosphorylation were recorded polarographically with a Clark-type electrode, while other measures were determined with standard fluorometric enzymatic methods. Results: Progressive impairment of liver mitochondrial respiration in the initial stage of ammonia-induced hepatotoxicity and the subsequent energy crisis due to decreased ATP synthesis lead to cessation of gluconeogenesis and ketogenesis. Reduction in glucose and ketone body supply to the brain is a terminal event in liver toxicity, preceding the development of coma. Conclusions: Our study provides a framework to further explore the relationship between hepatic dysfunction and progression of brain energy crisis in hepatic encephalopathy.

Development of liposome as a novel adsorbent for artificial liver support system in liver failure

Artificial liver support systems (ALSS), represented by albumin dialysis, are designed to replace the liver detoxification function and to serve as supportive therapy until liver transplantation or liver regeneration. We introduce liposome, which is majorly formed by soybean lecithin as the adsorbent nanomaterial in dialysate for the removal of protein-bound and liver failure-related solutes. The binding rate was detected by ultrafiltration column. In vitro and in vivo dialysis was performed in a recirculation system. Unconjugated bilirubin (52.83–99.87%) and bile salts (50.54–94.75%) were bound by liposomes (5–80 g/L) in a dose–response relationship. The in vitro haemodialysis model showed that the concentration of unconjugated bilirubin (45.64 ± 0.90 μmol/L vs. 54.47 ± 3.48 μmol/L, p < 0.05) and bile salts (153.75 ± 7.72 μmol/L vs. 180.72 ± 7.95 μmol/L, p < 0.05) were significantly decreased in the liposome dialysis group than in the phosphate buffer saline group. The in vivo haemodialysis model showed that 40 g/L liposome-containing dialysate led to a significant higher reduction ratio in total bilirubin (6.56 ± 5.72% vs. −1.86 ± 5.99%, p < 0.05) and more total bile acids (7.63 ± 5.27 μmol vs. 2.13 ± 2.32 μmol, p < 0.05) extracted in the dialysate in comparison with the conventional dialysate. In conclusion, the liposome-added dialysate proved to impose good extraction effects on the unconjugated bilirubin and bile salts. These findings indicate that conventional dialysate supported by this nanomaterial can markedly improve the removal of protein-bound and liver failure-related solutes, thus suggesting a novel and promising liver dialysis system.

Роль модификаций липидов тканей печени в патогенезе хирургического эндотоксикоза

Цель. Оценка роли модификаций липидов тканей печени в ее детоксикационной способности при остром перитоните. Методика. В эксперименте у собак моделировали острый перитонит различной степени тяжести. Степень эндогенной интоксикации оценивали по уровню токсических продуктов гидрофильной и гидрофобной природы. Представлен новый способ оценки детоксикационной функции печени на основе определения уровня токсических продуктов в крови, притекающей к органу и оттекающей от него. Для характеристики качественного и количественного состава липидов из биопсийного материала печени выделяли липиды, осуществляли их фракционирование и денситометрию. Оценивали интенсивность перекисного окисления липидов, активность фосфолипазы А2 и супероксиддисмутазы. Результаты. Показано, что функциональное состояние печени при хирургическом эндотоксикозе коррелирует с модификацией липидов ее тканевых структур, проявлением чего были существенные изменения состава основных липидов и резкое увеличение хаотропных фракций. Установлена сопряженность изменений состава липидов тканей печени со степенью тяжести патологического процесса. Одними из значимых триггерных механизмов липиддестабилизирующих явлений в тканевых структурах печени являются оксидативный стресс и высокая фосфолипазная активность. При тяжелом течении острого перитонита высока вероятность такого нарушения функционально-метаболического состояния печени, при котором она приобретает самостоятельное патогенетическое значение в продукции токсических субстанций. Заключение. В патогенезе синдрома эндогенной интоксикации при остром перитоните важную патофизиологическую значимость имеет модификация липидов тканей печени, которая является основой острой печеночной недостаточности и формирования нового состояния органа - источника токсинов. Полученные данные определяют векторы патогенетической терапии по предупреждению необратимых повреждений печени с высоким риском неблагоприятного исхода. Background. Despite the interest to the issue of surgical endogenous intoxication, mechanisms of impaired hepatic detoxification function in endogenous intoxication induced by acute peritonitis are studied insufficiently. Aim. To elucidate the role of modifications in membrane lipids of liver cells in imparing its detoxification ability in acute peritonitis. Methods. Acute peritonitis of different severity was modeled in dogs. The authors presented a new method for evaluating the liver detoxification function based on measuring concentrations of toxic products in the blood inflowing to and outflowing from the liver. Hepatic lipids were separated, fractionated and studied by densitometry. The qualitative and quantitative composition of liver lipids, intensity of lipid peroxidation, and activities of phospholipase A2 and superoxide dismutase were measured in liver tissue in the dynamics of experimental peritonitis. Results. In surgical endogenous intoxication, the liver function correlated with the modifications of tissue lipids evident as considerable changes in the composition of major membrane-forming lipids and an increase in chaotropic fractions (fatty acids, lysophospholipids). Changes in the tissue lipid composition correlated with severity of the pathological process. Significant triggering mechanisms for the hepatic lipid modification were oxidative stress and a high phospholipase activity. Conclusion. In severe acute peritonitis, there is a high probability of profound functional and metabolic disorders in the liver so that it acquires an independent pathogenetic significance as a producent of toxic substances.

ENDOTOXINEMIA, DYSREGULATION AND THE PRE-ILLNESS FORMATION

The study of the conditions of pre-illness and early stages of the disease, as well as their mechanisms, are of particular relevance for modern preventive medicine. It is known that dysregulation is the basis of many pathological processes, the leading link in the pathogenesis of which is endotoxinemia, the severity of which is largely determined by the state of detoxification liver function. The aim of the study was to elucidate the significance of the liver detoxification function and endotoxinemia in the occurrence of dysregulation and the pre-illness formation. In experiments on rats and rabbits it was is established that the direction and nature of changes in the processes of heat exchange, energy and plastic supply of the organism, their hormonal and humoral regulation under the action of E. сoli endotoxin (LPS) depend on the severity of endotoxinemia, the state of detoxification liver function. It is shown that in conditions of functional liver failure, the action of LPS in the body in trace concentrations is accompanied by an increase, and with severe endotoxinemia, a decrease in the activity of the processes of energy and plastic supply of the organism, detoxification. It was found that the ambiguous direction and nature of the changes in the processes of heat exchange, energy and plastic supply of the organism, their neurotransmitter, hormonal and humoral regulation under conditions of endotoxinemia depend on its severity and are largely due to a decrease in the level of arginine in blood plasma and cerebrospinal fluid. In experiments on rats it was revealed that the central action of 1-noradrenaline (10 μg) under the conditions of preliminary introduction of L-arginine hydrochloric acid (100 μg) into the brain ventricles (for 15 min) exerts a more pronounced and prolonged decrease in body temperature in comparison with control, while the duration and severity of the hypothermic effect from the introduction of acetylcholine into the brain ventricles at a dose of 2.5 μg with eserine (5 μg) decreased. It was found that in conditions of bacterial endotoxinemia, accompanied by an increase in body temperature and a decrease in the level of arginine in blood plasma and cerebrospinal fluid in rabbits, intensive utilization of 14C-arginine hydrochloric acid from tissues of the hypothalamus takes place. Endotoxinemia is a key link in the pathogenesis of disregulatory pathology and a universal factor in the development of such a condition as pre-illness.

HEPATOPROTECTIVE ACTIVITY OF SPERMATOZOID STIMULATOR — KATIAZYN UNDER CONDITIONS OF EXPERIMENTAL PARACETAMOL-INDUCED LIVER PATHOLOGY

It was investigated hepatoprotective properties of camphor acid derivative — katiazin under experimental model conditions of paracetamol drug-induced hepatitis. It was proved that katiazin in two doses (10 and 50 mg/kg body weight) stimulates the non-enzymatic antioxidant defense unit, increasing the concentration of the reduced glutathione and sulfhydryl groups. The application of katiazin led to an increase in the prothrombin time, which can be interpreted as a sign of the compound anticoagulant effect. It was found out that the administration of katiazin enhances liver detoxification function, normalizes carbohydrate and lipid metabolism in rats.

Nutritional State Impact on the Liver Detoxification Function in Patients Infected by HIV under Antiretroviral Drugs at the Bertoua Day Hospital of Cameroon

The present study aimed at evaluating the nutritional state impact on liver detoxification function in patients infected by the human immunodeficiency virus under antiretroviral drugs. We performed a retrospective and prospective transversal survey on the patients infected by the human immunodeficiency virus, under antiretroviral drugs at the Bertoua day hospital. The retrospective period of our survey went from October 24, 2014 to February 24, 2014 (4 months) and the prospective shutter of the survey went from February 24, 2014 to August 24, 2014 (6 months), a total period of 10 months. We also analysed the socio-demographics parameters (Age and Sex), Biological parameters (HIV type, CD4, Transaminases) and the therapeutics parameters (Therapeutic protocol, Evolution). The hepatic affection has been judged by the remarkable increase of the rate of transaminases (>3N) and by the appearance of hypersensitivity signs (Skin rashes, Fever…). During this survey, 38 hepatic-toxicity cases caused by the intake of ARV drugs were collected. We included 12 men (31.58%) and 26 women (68.42%) with a sex-ratio of 0.46 in favor of the women. The average age was 45.68±13.13 year with age ranging between 10 to 65 years. Age group of 50 years and above was most represented with a percentage of 42.10. The majority of the patients were infected by the HIV 1 (86.85%) against 10.52% for the HIV 2 and 2.63% for the HIV 1+2. The most prescribed therapy was the association of 2 INTI+1 INNTI (Tenofovir+Lamivudine+Nevirapine) and the AIDS stage represented 7.89%. Prior to the antiretroviral therapy, the 38 patients had normal transaminases that followed modifications of the initial therapeutic protocol after a remarkable increase during the antiretroviral therapy. We noted during this survey that the hepatotoxicity intervention of our patients under ARV drugs was correlated to their Body Mass Index (BMI) that allowed us to evaluate the nutritional state of our patients. The intervention of the hepatotoxicity during the antiretroviral therapy, among the HIV patients having a good nutritional state (normal BMI), was very weak in the absence of the predisposing factors.

Recent advances in management of acute liver failure.

Acute liver failure (ALF) is a life-threatening illness, where a previously normal liver fails within days to weeks. Sudden loss of synthetic and detoxification function of liver results in jaundice, encephalopathy, coagulopathy, and multiorgan failure. The etiology of ALF varies demographically. The mortality of ALF is as high as 40–50%. The initial care of patients with ALF depends on prompt recognition of the condition and early detection of etiology. Management includes intensive care support, treatment of specific etiology if present and early detection of candidates for liver transplantation. Liver transplantation remains the only therapeutic intervention with proven survival benefit in patients with irreversible ALF. Living related liver transplantation, auxiliary liver transplantation, and ABO-incompatible liver transplantation are coming up in a big way. Liver assist devices and hepatocyte transplant remain experimental and further advances are required. Public health measures to control hepatitis A, B, E, and drug-induced liver injury will reduce the incidence and mortality of ALF.

Clinical observation of adefovir dipivoxil combined with Anluohuaxian pill in the treatment of chronic hepati-tis B cirrhosis

Objective To explore the clinical effect of adenovirus dipivoxil combined with Anluohuaxian pill in the treatment of chronic hepatitis B cirrhosis .Methods 98 patients with chronic hepatitis B liver cirrhosis were randomly divided into the two groups .49 cases in the control group were treated with adenovirus dipivoxil ,and 49 ca-ses in the observation group were given adenovirus dipivoxil combined with Anluohuaxian pill .The clinical effect of two groups was observed .Results The total effective rate of the observation group was 92.9%,which was significant-ly higher than 69.4% of the control group （χ2 =9.37,P0.05）.After treatment,the ALT,HA and A/G of the two groups were significantly improved compared with those before treatment ,the improvement of the observation group was better than control group ,the difference was statistically significant （ t=11.302 1,9.012 1,7.312 4,all P〈0.05）.Conclusion In clinical practice,adenovirus dipivoxil combined with Anluohuaxian pill in the treatment of patients with chronic hepatitis B cirrhosis has good therapeutic effect ,it can improve the clinical symptoms and pa-tients＇liver function ,so as to improve the liver detoxification function and the clinical treatment effect ,which worthy of clinical application and promotion . Key words: Chronic hepatitis B cirrhosis; Adenovirus dipivoxil; Anluohuaxian pill

Monitoring of liver function in patients with fatty liver disease in combination with coronary heart disease and type 2 diabetes

The aim of the study was to examine the liver detoxification function by comparing a 13C- methacethine breath test, with a Forns formula and with liver transaminases in patients with coronary heart disease and type 2 diabetes mellitus in combination with nonalcoholic fatty disease Comparisons of the rates of metabolism (p &lt;0.01) between cumulative dose at 40 minutes (p &lt;0.01) with those at 120 minutes (p &lt;0.01), in two groups of patients displayed more signs of steatohepatitis than signs of steatosis. Use of the 13C-methacetine test to diagnose pathological changes in the liver in the early stages of NAFLD (steatosis, steatohepatitis) is positively correlated with the Forns formula. It is likely to find fibrosis of the liver when Forns formula is over 4.25, 13C-breath test at least 10%, lower levels of ALT and bilirubin, and elevated triglycerides contrary.

Evaluation of the Potential Effect of Transgenic Rice Expressing Cry1Ab on the Hematology and Enzyme Activity in Organs of Female Swiss Rats

To assess the safety of transgenic rice expressing Cry1Ab protein to vertebrates, the effect of Cry1Ab rice on broad health indicators in blood and various organs of Swiss rats were analyzed. The 30 and 90 day safety studies of Cry1Ab rice on female Swiss rats revealed that Cry1Ab rice had no significant effect on the several elements of blood lymph including hemogram, calcium ion concentration and apoptosis rate of lymphocytes, indicating that Cry1Ab protein could not affect the blood lymph of Swiss rat. Similarly, Cry1Ab rice had no effect on enzyme activities in a variety of organs of Swiss rat. However, Cry1Ab rice did have significant effects on the blood biochemistry indexes including urea, triglyceride (TG), glutamic oxalacetic transaminase (AST) and alkaline phosphatase (ALP) after the rats were fed with Cry1Ab rice for 30 days, but not after 90 days, indicating that Cry1Ab protein may influence blood metabolism for a short duration. Quantitative real-time PCR (qPCR) analysis of the 6 genes encoding enzymes responsible for the major detoxification functions of liver revealed that Cry1Ab rice exerted no influences on the levels of these transcripts in liver of Swiss rat, indicating that significant differences registered in part of the blood biochemical parameters in the 30 day study might result from other untested organs or tissues in response to the stress of exogenous Cry1Ab protein. The results suggest that Cry1Ab protein has no significant long-term (90 day) effects on female Swiss rat.

Cryopreserved Fetal Liver Cell Transplants Support the Chronic Failing Liver in Rats with CCl4-Induced Cirrhosis

Hepatocyte transplantation is a promising method for supporting hepatic function in a broad spectrum of liver diseases. The aim of this work was to test the efficacy of human fetal liver cells to support the chronic failing liver in an experimental model of carbon tetrachloride (CCl4)-induced cirrhosis in rats. Liver cirrhosis was induced by intraperitoneal administration of CCl4 at a dose of 0.2 ml (50% v/v solution)/100 g body weight, twice a week for 3 months in rats. Ten days after stopping CCl4 administration (experimental day 0), rats received intrasplenic injection of cryopreserved fetal liver cells (FLC, 1 x 10(7) cells in 0.3 ml medium). As a cirrhotic control group, CCl4-induced cirrhotic rats were used with intrasplenic injection of an equal volume of medium alone. Animals were sacrificed on experimental day 15. Human fetal liver cell transplantation almost completely prevented the death of cirrhotic animals during the 2 weeks after treatment, while high ongoing mortality was seen in the cirrhotic control group. Cell transplantation into the spleen normalized total bilirubin and TBARSs levels and increased albumin levels in blood serum, as well as restoring mitochondrial function and liver detoxification function (assessed by cytochrome P450 contents and activity) compared with the activities seen in the cirrhosis control group. In parallel with this restoration of biochemical and functional liver indices, morphological patterns of liver recovery or regeneration after liver cell transplantation were demonstrated in day 15 samples by light microscopy. These were absent in the group that had received only medium alone.