Effects of glibornuride versus metformin on eye lenses and skin in experimental diabetes

The aim of the study was to investigate the effect of glibornuride (CAS 26944-48-9) and metformin (CAS 657-24-9) on eye lenses and skin of streptozotocin (STZ)-induced diabetic rats. The drugs were administered daily to one diabetic and one control group separately from day 14 to day 42. After 42 days, diabetes caused significant increases in blood glucose levels, non-enzymatic glycosylation (NEG) of skin and lens proteins and skin lipid peroxidation (LPO) levels as well as decreases in body weights and lens glutathione (GSH) levels. Metformin administration to the diabetic rats produced more significant reduction in blood glucose than glibornuride. Metformin produced non-significant increase in NEG levels in lenses and skin. Unlike metformin, glibornuride increased NEG levels significantly in lenses. Both drugs produced non-significant increase in lens GSH levels and decreases in skin LPO levels in diabetic rats. Sodium dodecyl sulphate (SDS) polyacrylamid gel electrophoresis revealed no significant difference in any of the protein bands between any of the groups. These observations suggest that metformin and glibornuride as oral antidiabetics have similar protective effects on tissues in STZ induced diabetic rats.     

Clinical trial of glibornuride in diabetes.

Glibornuride is an addition to the second-generation sulphonylureas, that has been shown in clinical trials to be effective and non-toxic. Twenty-three diabetics who were poorly controlled on other oral hypoglycaemic agents and seven newly diagnosed diabetics were treated with glibornuride. The efficacy and lack of toxicity of this drug was confirmed, but there was no evidence to suggest that it is significantly more potent than other sulphonylureas. It does not seem to represent a significant therapeutic advance.     

Effect of prenatal and perinatal acrylamide on the biochemical and morphological changes in liver of developing albino rat

Acrylamide has been employed as an experimental probe to investigate biochemical and morphological changes in developing rat liver following toxin administration in pregnant rats. Non-anesthetized pregnant rats were given acrylamide by gastric intubation at a dose of 10 mg/kg/day. The pups were divided into three groups: Group A, mothers were treated with saline (control group); Group B, mothers were treated with acrylamide from day D7 of gestation till birth (prenatal intoxication); Group C, mothers were treated with acrylamide from D7 of gestation to D28 after birth (perinatal intoxication). Acrylamide-induced biochemical changes (in liver and serum) and morphological changes (in liver) were studied in control and acrylamide-treated developing pups. Prenatally and perinatally administered acrylamide significantly increased lipid peroxidation and reduced glutathione and total thiol levels in liver. Significant inhibition of peroxidase and superoxide dismutase activities was observed in liver tissue. Total lipids including cholesterol and triglycerides were significantly increased in the serum. Acrylamide treatment increased serum alanine aminotransferase and aspartate aminotransferase activities and inhibited alkaline phosphatase activity. Sodium and potassium concentrations were increased, but calcium, phosphorus and iron levels were significantly reduced in the serum. Acrylamide produced significant electrophoretic changes in serum proteins. The most noticeable change was splitting of β-globulin into β1- and β2-globulins. Light microscopy showed acrylamide-induced fatty deposits, congested central vein, vacuolization and chromatolysis in hepatocytes. Ultrastructural studies revealed vacuolated cytoplasm, lipid droplets of variable size and mitochondria with damaged cristae and vacuolization. The nuclei in acrylamide-treated groups showed marked decrease in the staining of nuclear DNA.     

Histochemical and biochemical observations on the cytotoxicity of paracetamol and its effects on glycogen metabolism in rat liver

The effects of paracetamol overdose on glycogen metabolism in rat liver have been investigated and related to its cytotoxicity. Paracetamol was administered to male rats by gavaging after a 24-h fast and refeeding was not permitted. An early (9-12-h) increase in histochemically demonstrable glycogen phosphorylase alpha activity in perivenous hepatocytes preceded major loss of membrane integrity as assessed by serum glutamate-pyruvate transaminase (SGPT) activity and uptake of trypan blue during perfusion. These changes occurred only after a decrease in the concentration of reduced glutathione, which is generally observed about 4 h after paracetamol treatment. The activation of glycogen phosphorylase in perivenous hepatocytes occurred concurrently with an increase in glycogen content of periportal hepatocytes, indicating a clear heterogeneity in the response of the two-cell populations to the hepatotoxin. The use of trypan blue perfusion together with histochemical techniques allowed changes in glycogen content and phosphorylase alpha activity of individual hepatocytes to be assessed with reference to the extent of membrane damage evident. The relevance of the results to possible mechanisms of hepatotoxicity is discussed.     

The effects of miconazole on rat liver mitochondria

The antifungal agent Miconazole nitrate has been shown to cause uncoupling and at higher concentrations an inhibition of oxidative phosphorylation in isolated rat liver mitochondria, with concurrent damage to the mitochondrial membranes.     

Effect of experimental diabetes on epidermal growth factor (EGF) receptors in the rat liver

The effect of streptozotocin-induced diabetes on 125I-labeled epidermal growth factor (EGF) binding was studied in microsomal membranes from rat liver. The binding of EGF in membranes from diabetic animals was significantly low, the value being about 60% of the control level. Scatchard analysis of the binding data clearly showed that the decrease in EGF binding was due to a decrease in the number of receptors. Treatment of diabetic animals with insulin restored EGF receptors to control levels, whereas the treatment with triiodothyronine had no effect. Serum EGF concentrations measured were almost the same among the control, diabetic, and insulin-treated diabetic groups. These results suggest that insulin deficiency in vivo causes a decrease in hepatic EGF receptors.     

The effects of flavonoids on rat liver during chronic palloidin intoxication/Morphological and biochemical studies (author's transl)

Continuous intraperitoneal administration of phalloidin (0.5 mg/kg body weight/day) leads to an alteration of intracellular contractile acto-myosinfilaments in rat liver. The hepatocytes show an accumulation of fibrillar material with some loss of contractile function of the pericanalicular web. Biochemically an increase of serum transaminases and alkaline phosphatase occurs. Histochemically the liver exhibitis changes in the distribution of some hepatocellular enzymes. The influence of the flavonoid (+)-cyanidanol-3 on these phalloidin-induced lesions was studied by histochemical, immunofluorescence and biochemical methods. The results imply, that (+)-cyanidanol-3 is probably protecting the plasma membrane of hepatocytes and therefore reduces the entrance of phalloidin into the cytoplasm. In addition an increased activity of the reticuloendothelial system was observed, perhaps resulting from the flavonoid administration. Both effects could be discussed as mechanisms of flavonoid action in the liver.     

Protective effects of glurenorm (gliquidone) treatment on the liver injury of experimental diabetes

Oxidative stress plays an important role in chronic complications of diabetes mellitus, and hence the regulation of free radicals is essential in the treatment of diabetes. The aim of the current study is to investigate the effect of glurenorm (10 mg/kg) on liver tissue in experimental diabetes. Diabetes was induced by intraperitoneal injection of 65 mg/kg streptozotocin. Glurenorm was administered to one diabetic and one control group separately, from days 14 to 42. On day 42, cardiac blood samples and liver tissue were taken from each rat. In diabetic rats, blood glucose, serum alkaline phosphatase and serum amino transferase activities, serum uric acid, serum sodium and potassium levels, liver nonenzymatic glycosylation, and lipid peroxidation increased, whereas body weight and liver glutathione levels decreased. The diabetic group given glurenorm blood glucose, serum alkaline phosphatase and aminotransferase activities, serum uric acid, sodium and potassium, liver nonenzymatic glycosylation, and lipid peroxidation levels decreased, and liver glutathione levels increased. As a result of all the biochemical findings obtained, it was concluded that glurenorm has a protective effect on damage of liver of streptozotocin-induced diabetes in rats.     

Comparison of acute response to polychlorinated biphenyl in liver of rat and channel catfish: a biochemical and morphological study.

The acute response of liver of channel catfish and rat to polychlorinated biphenyl was compared on a structural and functional basis. Both the rat and the fish had elevated microsomal enzyme activities. However, in the rat the response was quantitatively greater in all respects. Morphologically, rats responded with lipid accumulation and marked increases in smooth endoplasmic reticulum. Fish liver showed lipid accumulation and increased profiles of rough endoplasmic reticulum with alterations in arrangement that appeared as vesicles and parallel cisternae. Minimal changes were seen in smooth endoplasmic reticulum, which appeared to be increased as discrete foci.     

正丁酸钠对大鼠肝脏缺血再灌注损伤的保护作用的研究

目的：观察正丁酸钠拮抗高迁移率族蛋白B1（HMGB1）表达对大鼠肝脏缺血再灌注损伤中的保护作用。方法：建立大鼠肝脏缺血再灌注模型．将40只雄性Wistar大鼠随机先分成5组（n-8）：假手术组,缺血组,预处理组、治疗1组、治疗2组。分别于缺血再灌注6h前后给药观察血清AST、ALT、TNF—α水平及肝组织HMGB—1含量变化,并行肝组织病理学检查。结果：缺血再灌注组中HMGB—1的含量高,预处理组、治疗1组、治疗2组这三组中相应时间点的HMGB-1含量、AST、ALT水平、TNF—α含量均较缺血再灌注组中低,预处理组较治疗1组、治疗2组效果显著且肝细胞病理损害较轻。结论：正丁酸钠预处理组对肝脏缺血再灌注损伤具有明显的保护作用。     

Hepatoprotective effects of Cassia semen ethanol extract on non-alcoholic fatty liver disease in experimental rat

Context: Cassia semen (Cs), a seed of Cassia obtusifolia L. (Leguminosae), is a popular functional beverage. Previous studies reported that Cs displayed antioxidant, antifungal and strong liver protective effects.

Objective: This study evaluates the hepatoprotective effects of Cs on non-alcoholic fatty liver disease (NAFLD).

Materials and methods: Seventy-two male Wistar rats raised with high-fat diet (HFD) were randomly allotted into model, metformin (0.2?g/kg) and Cs (0.5, 1, and 2?g/kg)-treated groups. Another 12 rats were raised with normal feed as control group; all the rats were orally administrated with drugs and vehicle for 6?weeks. Alanine transferase (ALT), aspartate transaminase (AST), triglycerides (TG), total cholesterol (TC), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 and low density lipoprotein receptor (LDL-R) mRNA levels were measured at the end of the experiment.

Results: Twelve weeks of HFD administration significantly increased the levels of AST, ALT, TG, TC, TNF-α, IL-6, IL-8 and MDA, decreased SOD (199.42 vs. 137.70?U/mg protein) and GSH (9.76 vs. 4.55?mg/g protein) contents, compared to control group. Cs administration group significantly decreased the elevated biomarkers with the ED₅₀?=?1.2?g/kg for NAFLD rats. Cs treatment also prevents the decreased expression of LDL-R mRNA, and improved the histopathological changes compared to model group.

Conclusions: The hepatoprotective effect of Cs on NAFLD may possibly be due to its antioxidant effect. Cs may become a potent hepatoprotective agent in clinical therapy in the future.     

The effects of vigabatrin on rat liver antioxidant status

The anti-epileptic drug vigabatrin was developed as an inhibitor of gamma-aminobutyric acid transaminase, and its ability to increase inhibition in the central nervous system led to its testing in an animal model. In animal models chronic use of vigabatrin is associated with irreversible myelin vacuolation. Antioxidant drugs change the antioxidant capacity of the body. Oxidative stress of the body increased when valproic acid and carbamazepine were used chronically. To assess whether vigabatrin may affect protein oxidation and lipid peroxidation, glutathione, glutathione peroxidase (GPx), and glutathione-S-transferase (GST) levels were studied in the livers of 57 rat fetuses after administration of vigabatrin to the mothers (19 in the first week of pregnancy, 20 in the second week, and 18 in the third week) and in 19 control rat fetuses without vigabatrin. We compared the results of administration of vigabatrin in each group with the controls. Rat fetus protein oxidation in group I (0.686 nmol/mg protein) and group II (0.723 nmol/mg protein) was higher than in the control group (0.388 nmol/mg protein). Lipid peroxidation (0.209, 0.224, 0.253 nmol/mg protein, respectively) and GPx levels (345.4, 329.0, 283.2 nmol/mg protein, respectively) of groups I, II, and III were higher than in the control group (0.104, 167.2 nmol/mg protein, respectively). GST in group II (79.2 nmol/mg protein) and group III (77.8 nmol/mg protein) were not different from that in the control group (78 nmol/mg protein). It was found that vigabatrin affected all the parameters that were studied, especially in group I, which was given the drug in the first week of pregnancy.     

Investigating the role of endogenous opioid system in chloroquine-induced phospholipidosis in rat liver by morphological,biochemical and molecular modelling studies

Drug-induced phospholipidosis (DIPL) is characterized by phospholipid storage in the lysosomes of affected tissues. Many severe effects and toxicities have been linked to DIPL. The aim of this study was to determine whether the endogenous opioid system is involved in chloroquine-induced phospholipidosis. The effect of naltrexone as an antagonist of opioid receptors in chloroquine-induced phospholipidosis in rat liver was investigated by morphological, biochemical, and molecular modelling studies. Transmission electron microscopy (TEM) showed that morphological characteristic changes of rat liver, including the number of lamellar bodies, grade of vacuolization and cell steatosis, were markedly attenuated in rats treated with naltrexone alone or in combination with chloroquine, in comparison with chloroquine-treated rats. The results of liquid chromatography mass spectrometry (LC/MS) showed that the concentrations of phenylacetylglycine (PAG) and hippuric acid (HA) were significantly decreased and increased, respectively, in target groups. Besides, the concentration ratio of PAG/HA was significantly decreased. Spectrophotometry resulted in a notable decrease in alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities in target groups. The results from the molecular docking and molecular dynamic simulation studies demonstrated clear chloroquine interaction with the active site cavity of the µ opioid receptor. These data suggest that administration of naltrexone alone, or in combination with chloroquine, notably attenuates the side effects of chloroquine-induced phospholipidosis, as well as demonstrating an increased probability of the endogenous opioid system involvement in chloroquine-induced phospholipidosis in rat liver.     

The metabolic effects of diuron in the rat liver

A systematic study on the effects of diuron on the hepatic metabolism was conducted with emphasis on parameters linked to energy metabolism. The experimental system was the isolated perfused rat liver. The results demonstrate that diuron inhibited biosynthesis (gluconeogenesis) and ammonia detoxification, which are dependent of ATP generated within the mitochondria. Conversely, it stimulated glycolysis and fructolysis, which are compensatory phenomena for an inhibited mitochondrial ATP generation. Furthermore, diuron diminished the cellular ATP content under conditions where the mitochondrial respiratory chain was the only source of this compound. Besides the lack of circulating glucose due to gluconeogenesis inhibition, one can expect metabolic acidosis due to excess lactate production, impairment of ammonia detoxification and cell damage due to a deficient maintenance of its homeostasis. Some of the general signs of toxicity that were observed in diuron-treated rats can be attributed, partly at least, to the effects of the herbicide on energy metabolism.     

胆宁片对实验性急慢性肝损伤的保护作用

目的：研究胆宁片对实验性小鼠急性肝损伤预防作用，及对大鼠慢性肝损伤的预防和治疗作用。方法：分别用D-氨基半乳糖和四氯化碳复制小鼠急性肝损伤和大鼠慢性肝损伤模型，检测小鼠和大鼠血清谷草转氨酶（AST）和谷丙转氨酶（ALT）的改变，观察胆宁片对大鼠血清总蛋白、白蛋白、A／G的影响、同时观察肝脏病理学改变。结果：胆宁片可明显抑制D-氨基半乳糖和四氯化碳引起的ALT、AST升高（P〈0．05或P〈0．01）；可显著升高四氯化碳引起的血清总蛋白和白蛋白含量降低（P〈0．05或P〈0．01）；肝脏病理组织学检查显示胆宁片可减轻肝细胞脂肪变性程度和纤维化程度。结论：胆宁片对小鼠D-氨基半乳糖急性肝损伤有较好的保护作用，对四氯化碳所致大鼠慢性肝损伤有一定的预防及治疗作用。