Liver Of Diabetic Rats Research Articles

Effect of aqueous-alcoholic extract of Ducrosia Anethifolia Boiss on the fetal liver of diabetic rats

Objective: Moshgak (Ducrosia anethifolia) is a wild plant with medicinal value. The present study aimed to evaluate the effect of Moshgak on the liver tissue of the diabetic rat fetus. Materials and Methods: In this animal study, the aqueous-alcoholic extract of Moshgak was prepared in the standard method. Forty rats were divided randomly into five groups, including control, sham, and three diabetic groups. The rats were diabetic with intraperitoneal injection of a single dose of streptozotocin (80 mg) and 2 diabetic groups were treated with Moshgak extract (280 and 560 mg/kg/bw) for 19 days. The rats were anesthetized and their blood was taken to measure the blood glucose, insulin, and malondialdehyde. Then, their fetuses were removed. The fetal liver sections were obtained by using the stereological methods. The micrometry of the liver tissue was performed and data were analyzed. Results: The finding showed a statistically significant increase (P < 0.01) in the total volume of liver, connective tissue, sinusoid, and hepatocytes in diabetic rats compared to control rats, while these parameters decreased significantly in treated groups with Moshgak. Hepatic cell count hepatic decreased in the treated groups. Furthermore, the changes in blood glucose, malondialdehyde, and insulin in diabetic rats were improved significantly by Moshgak treatment. The dilation of sinusoids, hepatocyte vacuolation, and mild lymphocytosis was observed in all diabetic groups except the treatment group with Moshgak 560 mg/kg/bw. Conclusions: According to obtained results, Moshgak extract was able to compensate partially the changes induced by diabetes in the fetal liver tissue. Therefore, due to the side effects of diabetes during pregnancy, further research on anti-diabetic properties of Moshgak is suggested.

Antioxidant Effect of Ethanol Extract of C. sativus on Streptozotocin-Induced Diabetic Rat Liver

The present study investigated the antioxidant effect of ethanol extract of Cucumis sativus on streptozotocin (STZ)-induced diabetic rat liver. Adult male Wistar albino rats (n = 25, mean weight = 215 ± 15 g) were randomly assigned to five groups of 5 rats each: normal control, diabetic control, metformin, 200 mg/kg body weight (bwt) extract and 300 mg/kg bwt extract groups. Diabetes mellitus was induced in the rats via intraperitoneal injection of 50 mg/kg bwt STZ. The diabetic rats were then treated for 21 days with either metformin (50 mg/kg bwt) or the extract at doses of 200 and 300 mg/kg bwt, respectively. Activities of antioxidant enzymes such as catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) as well as antioxidant molecules like retinoic acid, ascorbic acid and α-tocopherol were evaluated in liver homogenate. The results showed that induction of diabetes mellitus with STZ significantly increased the fasting blood glucose (FBG) concentrations of the rats (p < 0.05). However, treatment of the diabetic rats with the extract markedly reduced the FBG concentration and body weights of rats (p < 0.05). Treatment of diabetic Wistar rats with ethanol extract of C. sativus significantly increased activities of the antioxidant enzymes and molecules as well as concentrations of nitric oxide (NO), but it markedly reduced the concentrations of hepatic total protein (TP) and malondialdehyde (MDA) (p < 0.05). These results suggest that ethanol extract of the medicinal plant can enhance antioxidant defense in the liver of STZ-induced diabetic rats.

Mechanism of action of quercetin in regulating cellular autophagy in multiple organs of Goto-Kakizaki rats through the PI3K/Akt/mTOR pathway.

This experimental study investigated the protective function of quercetin on the liver, spleen, and kidneys of Goto-Kakizaki (GK) rats and explores its mechanism of action on autophagy-related factors and pathways. GK rats were randomly divided into three groups: DM, DM + L-Que, and DM + H-Que, with age-matched Wistar rats serving as the control group. The control and DM groups were gavaged with saline, and the quercetin-treated group was gavaged with quercetin for 8 weeks each. Weekly blood glucose levels were monitored. Upon conclusion of the experiment, blood samples were gathered for lipid and hepatic and renal function analyses. The histopathologic morphology and lipid deposition in rats were examined. Disease-related targets were identified using molecular docking methods and network pharmacology analysis. Subsequently, immunohistochemical analysis was performed, followed by Western blotting to evaluate the levels of autophagy-related proteins and proteins in the AKT/PI3K/mTOR pathway, as well as their phosphorylation levels. The results showed that, compared with the control group, the DM group exhibited significant increases in blood glucose, serum liver and kidney markers, liver fat vacuoles, and inflammatory cell infiltration. Immunohistochemistry (IHC) results indicated that quercetin reduced the extensive expression of AKT, P62, and mTOR in the liver and spleen of diabetic rats. The expression of autophagy and pathway-related proteins, such as P62, PI3K, P-PI3K, Akt, P-AKT, mTOR, and P-mTOR, was upregulated, while the expression of LC3A/LC3B, Beclin-1, Pink-1, and Parkin was downregulated. Conversely, the quercetin group showed a reduction in liver and kidney injury serum markers by decreasing lipid deposition and cell necrosis, indicating that quercetin has protective effects on the liver, spleen, and kidneys of GK rats. Additionally, in the quercetin group, the expression of autophagy and pathway-related proteins such as LC3A/LC3B, Beclin-1, Pink-1, and Parkin was upregulated, while the expression of P62, PI3K, P-PI3K, Akt, P-AKT, mTOR, and P-mTOR was downregulated, with statistically significant correlations. Quercetin markedly ameliorates liver, spleen, and kidney damage in GK rats, potentially through the inhibition of the PI3K/Akt/mTOR pathway, promoting autophagy. This research offers a rationale to the therapeutic potential of quercetin in mitigating organ damage associated with diabetes.

Effects of Hydrolysates of Aduwa (Balanites aegyptiaca Del.) Seed on Oxidative Stress in the Livers of Streptozocin-induced Diabetic Rats

Effects of Hydrolysates of Aduwa (<i>Balanites aegyptiaca</i> Del.) Seed on Oxidative Stress in the Livers of Streptozocin-induced Diabetic Rats

Protective Mechanism Pathway of Cinnamomum Zeylanicum at High Dosage against Liver and Renal Damage in STZ-Induced Diabetic Rats

INTRODUCTION: Cinnamon zeylanicum (CZ) bark is widely used as supplement for diabetic management, there are concerns about its safety and potential toxicity at high doses, and limited evidence to support its efficacy. To investigate this further, this study examines the effects of Cinnamon zeylanicum aqueous extract (CZAE) on various factors in diabetic rats, including body weight, blood glucose level, biochemical parameters, histological changes, and gene expression. MATERIALS AND METHODS: In the study, 30 male Sprague Dawley rats were divided into five groups of six animals each. Type 2 diabetes mellitus (T2DM) was induced in all groups except the negative control by a single intraperitoneal injection of streptozotocin (STZ). The rats in the intervention groups (Groups C, D, and E) were given CZAE at 1000, 1500, and 2000 mg/kg, dose respectively, for 28 days. The body weight and fasting blood glucose were monitored weekly, and their liver and renal profiles were analyzed. Histology was assessed with hematoxylin and eosin stain, and apoptotic gene expression was examined in liver and renal tissues. RESULTS: The body weight of rats in intervention groups increased compared to the control group. There was a significant decrease (P&lt;0.001) in blood glucose levels. The extract significantly reduced (P&lt;0.05) liver biochemical markers in the intervention groups compared to the control group. The histology of the liver &amp; kidney improved (p&lt;0.001) with upregulated Bcl-2 and down-regulated BAX genes in preventing apoptosis in the intervention groups. CONCLUSIONS: High doses of CZAE are safe and effective for T2DM.

The Effect of Single Clove Garlic Extract (Allium sativum) Against Aspartame-Induced Hepatotoxicity in Diabetic Rats

Background: Aspartame is a widely used synthetic sweetener used for dietary control and by diabetics. Objectives: This study aims to investigate the effect of a single garlic clove extract against aspartame-induced hepatotoxicity in diabetic rats. Methods: Forty-eight experimental male albino rats were randomly divided into eight groups (6 rats per group) as follows: Group (G)1: served as normal control and received distilled water orally, G2: rats treated with single clove garlic (SCG) extract (0.5 g/kg body weight), G3: rats were treated with SCG extract (0.5 g/kg body weight) and alkaline phosphatase (ALP) (200 mg/kg body weight), G4: rats treated with ASP (200 mg/kg body weight), G5: was the diabetic control group (induced by alloxan (ALX) 120 mg/kg body weight), G6: diabetic rats were treated with SCG extract (0.5 g/kg body weight), G7: diabetic rats were treated with SCG extract (0.5 g/kg body weight) and ASP (200 mg/kg body weight) and G8: diabetic rats were treated with ASP 200 mg/kg body weight. Results: The results obtained showed that treatment with ASP caused a significant increase in serum levels of serum alanine transaminase (ALT), aspartate transaminase (AST), and ASP in SCG extract-treated rats in G3 and G4 and diabetic rats in G7 and G8, while treatment with SCG extract caused a significant decrease in serum levels of ALT, AST and ALP in SCG treated rats in G2 and G6 and diabetic rats in G7 compared to the control group (G1). After treatment with ASP, histologic changes in the liver were observed in G4, which were more pronounced in G8, indicating liver damage compared to the control group, while treatment with SCG extract showed further changes in liver tissue in the diabetic rats of G7 and G8. Conclusion: The present study suggests that administering ASP in normal rats leads to liver dysfunction. Moreover, our results proved that the application of ASP in diabetic rats may cause additional damage compared to ASP in normal rats. This study demonstrated that treatment with SCG extract significantly attenuated the biochemical and histopathologic changes induced by ASP and alloxan. From the data obtained, it appears that treatment with SCG extract has a protective effect against the toxicity of ASF and alloxan on the liver of normal and diabetic rats.&#x0D;

A 4D Printed Adhesive, Thermo-Contractile, and Degradable Hydrogel for Diabetic Wound Healing.

Chronic wound healing remains a substantial clinical challenge. Current treatments are often either prohibitively expensive or insufficient in meeting the various requirements needed for effective diabetic wound healing. A 4D printing multifunctional hydrogel dressing is reported here, which aligns perfectly with wounds owning various complex shapes and depths, promoting both wound closure and tissue regeneration. The hydrogel is prepared via digital light process (DLP) 3D printing of the mixture containing N-isopropylacrylamide (NIPAm), curcumin-loaded Pluronic F127 micelles (Cur-PF127), and poly(ethylene glycol) diacrylate-dopamine (PEGDA575-Do), a degradable crosslinker. The use of PEGDA575-Do ensures tissue adhesion and degradability, and cur-PF127 serves as an antibacterial agent. Moreover, the thermo-responsive mainchains (i.e., polymerized NIPAm) enables the activation of wound contraction by body temperature. The features of the prepared hydrogel, including robust tissue adhesion, temperature-responsive contraction, effective hemostasis, spectral antibacterial, biocompatibility, biodegradability, and inflammation regulation, contribute to accelerating diabetic wound healing in Methicillin-resistant Staphylococcus aureus (MRSA)-infected full-thickness skin defect diabetic rat models and liver injury mouse models, highlighting the potential of this customizable, mechanobiological, and inflammation-regulatory dressing to expedite wound healing in various clinical settings.

IMPACT OF MELATONIN ON SOME INDICATORS OF CARBOHYDRATE METABOLISM IN LIVER OF RATS WITH DEXAMETHASONE-INDUCED DIABETES

One frequently employed experimental model, particularly in pre-clinical studies examining the hypoglycemic effects of potential antidiabetic medications, is the metasteroid diabetes model induced by the prolonged administration of glucocorticoids to animals. This experimental study aimed to elucidate the effects of exogenous melatonin (10 mg/kg) on glycogen content and the activity of key enzymes—pyruvate kinase (PK) [EC 2.7.1.40], lactate dehydrogenase (LDH) [EC 1.1.1.27], glucose-6-phosphate dehydrogenase (G-6-PDH) [EC 1.1.1.49], and glucose-6-phosphatase (G-6-P-ase) [EC 3.1.3.9]—in the livers of rats with dexamethasone-induced diabetes. Materials and Methods. The experiments were performed on 44 male 18-month-old white non-linear rats, divided into three groups: 1) control (intact rats), 2) rats with dexamethasone-induced diabetes, 3) rats that amid the progression of dexamethasone-induced diabetes, underwent daily oral administration of melatonin (Sigma, USA) in a dose of 10 mg/kg. Dexamethasone diabetes was modeled by subcutaneous injection of dexamethasone (injection solution 4 mg/ml, KRKA, Slovenia) at a dose of 0.125 mg/kg body weight daily for 13 days (O.V. Stefanov, 2001). Decapitation of animals was carried out in accordance with the norms of the "European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes" (Strasbourg, 1986). Glucose content in blood from the tail vein of rats, taken on the 14th day of fasting before decapitation of the animals, was determined using a portable glucometer (One Touch Ultra Easy, Life Scan, USA). The content of glycogen and the activity of the studied enzymes of carbohydrate metabolism in the liver were determined according to the generally accepted, previously described methods. A 5% homogenate was prepared from the cold-isolated rat liver in a chilled 50 mM Tris-HCI buffer (pH=7.4) to study the activities of pyruvate kinase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase in the cytosolic fraction. The reliability of the difference between the obtained indicators was assessed using the parametric Student's t-test (for normal distribution) and the non-parametric Mann-Whitney U-test (for non-normal distribution). Differences were considered probable at p≤0.05. Results and discussion. According to our results, in the liver of diabetic rats that did not receive any means of correction of carbohydrate metabolism disorders, the glycogen content was 33% lower than in intact animals. The activities of enzymes such as pyruvate kinase and glucose-6-phosphate dehydrogenase were also reduced in the liver of rats with impaired glucose tolerance by 31.6 and 21.5%, respectively, compared to intact animals, indicating inhibition of glucose oxidation pathways, both at the level glycolysis (decrease of pyruvate kinase), as well as at the level of the oxidative stage of the pentose-phosphate pathway of glucose-6-phosphate oxidation. At the same time, the activity of lactate dehydrogenase and especially glucose-6-phosphatase in the liver of rats with diabetes by 19.5 and 56%, respectively, exceeded the indicators of animals of the control group, which demonstrates the increased activity, intensity of glycogenolysis and gluconeogenesis under conditions of insulin resistance, because glucose-6-phosphatase is the terminal enzyme of these processes. Regarding the investigated parameters of carbohydrate metabolism, both the glucose content in the blood of rats, as well as the glycogen content and the activity of all studied enzymes in the liver of rats that were injected with melatonin against the background of the development of diabetes, did not reliably differ from the parameters of intact animals, which confirms the assumption of the probable hypoglycemic effect of melatonin against the background of the development of diabetes. Conclusions: The daily two-week use of melatonin (10 mg/kg), against the background of the development of dexamethasone diabetes in rats, contributes to the normalization of certain indicators of carbohydrate metabolism in the liver of animals.

Hepatic insulin synthesis increases in rat models of diabetes mellitus type 1 and 2 differently.

Insulin-positive (+) cells (IPCs), detected in multiple organs, are of great interest as a probable alternative to ameliorate pancreatic beta-cells dysfunction and insulin deficiency in diabetes. Liver is a potential source of IPCs due to it common embryological origin with pancreas. We previously demonstrated the presence of IPCs in the liver of healthy and diabetic rats, but detailed description and analysis of the factors, which potentially can induced ectopic hepatic expression of insulin in type 1 (T1D) and type 2 diabetes (T2D), were not performed. In present study we evaluate mass of hepatic IPCs in the rat models of T1D and T2D and discuss factors, which may stimulate it generation: glycaemia, organ injury, involving of hepatic stem/progenitor cell compartment, expression of transcription factors and inflammation. Quantity of IPCs in the liver was up by 1.7-fold in rats with T1D and 10-fold in T2D compared to non-diabetic (ND) rats. We concluded that ectopic hepatic expression of insulin gene is activated by combined action of a number of factors, with inflammation playing a decision role.

ß- Caryophyllene Ameliorates Insulin Resistance in Liver of High Fat Diet and Fructose-Induced Type-2 Diabetic Rats

Insulin resistance may impact organs that transmit insulin signals, like skeletal muscle, adipose tissue, and the liver. Hyperglycemia and hypertriglyceridemia in the fasting state of type 2 diabetes mellitus are more significantly impacted by insulin resistance in the liver. Hypertriglyceridemia is the culprit behind beta-cell failure in type 2 diabetes. Treating insulin resistance in liver as a primary mechanism of traditional antidiabetic drugs, but unfortunately traditional drugs has unalterable advisory effect. In the present research, insulin resistance in the liver is addressed with the versatile natural phytonutrient beta-caryophyllene to demonstrate effectiveness in managing diabetes. An effective dose of -Caryophyllene taken by non-parental route (200 mg/kg b.wt) was given for 30 days to experimentally induced (high-fat diet and fructose-fed) type-2 diabetic rats to find out whether β-Caryophyllene regulates the IRS-2/akt pathway of insulin signaling. In the liver of diabetic rats, the data demonstrates that ß-caryophyllene treatment significantly increased the mRNA and protein expression of insulin receptor (IR) and GLUT-2. However, there was a significant variation in the mRNA expression of akt and insulin receptor-substrate-2 (IRS-2) between groups. Taking caryophyllene supplements can be beneficial for the control of type 2 diabetes. Studies conducted with this sesquiterpene could have tremendous potential and benefit for the treatment of type 2 diabetes.

Ectopic expression of insulin in a type 1 diabetic rat model by injection of manipulated mesenchymal stem cells with an insulin construct driven by a glucose-sensitive promoter in the port vein.

The treatment of type 1 diabetes through islet cell transplantation is a complex process, facing challenges such as allograft rejections and a limited supply of donors. One potential solution is to utilize the liver as an alternative for natural insulin production, as hepatocytes can secrete proteins and respond to glucose levels. Recent research has shown promising results in using mesenchymal stem cells as a potential cure for diabetes. The study utilized a diabetic rat model, confirmed through blood sugar measurement. A plasmid vector was designed with specific genetic components, synthesized by biotech company, and then Inserted vector into a plasmid with resistance genes and bacterial origin. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were cultured and transfected with the plasmid using Lipofectamine 3000. Polymerase chain reaction wasemployed to confirm successful transfection using specific primers. For the animal study, 30 male Wistar rats were divided into six groups, each comprising five rats. The control group did not receive any treatment, while the second group received MSCs via Portal Vein Injection. The third group received MSCs transfected with a specific construct via Portal Vein Injection. The fourth group was induced to develop diabetes through streptozotocin(STZ) injection, the fifth group developed diabetes and received untransfected MSCs via Portal Vein Injection, and the sixth group received MSCs transfected with the specific construct via Portal Vein Injection. To manage Pain, appropriate pain control was administered to the rats for 3 days after the surgery. Fixed liver tissues obtained from the euthanized rats were utilized for immunohistochemistry. In this study, immunohistochemical techniques were used to examine insulin expression in different groups of rats. The control groups showed high levels of insulin expression, while the diabetic groups exhibited lower expression. However, there was a significant difference between the diabetic groups treated with MSC and transgenic MSC cells. All groups had similar baseline glucose levels, but the diabetic groups showed a significant increase after STZ injection, whereas the control and MSC groups did not. Postintervention, both the control and MSC groups had similar glucose levels to the post-STZ levels. However, diabetes-induced groups experienced a significant decrease in glucose levels, with the transfected MSCs showing a greater decrease than the untransfected MSCs. The study suggested that treatment with MSCs, especially transfected ones, can effectively reduce glucose levels in rats with diabetes. In this research, rat BM-MSCs were utilized to create insulin-producing mesenchymal cells with glucose-sensitive insulin expression. The cells were transferred to the liver of diabetic rats via portal vein injection, leading to an increase in insulin expression. This study proposes a novel approach for cell therapy and delivery in the treatment of type 1 diabetes.

1H NMR metabolomics techniques demonstrated the effectiveness of methoxy substituted 2-benzylidene-1-indanone, A1 and A2A Adenosine Receptor antagonists, in modulating glucose production in the liver of diabetic rats

The physiological function of the liver in the overall disposal of postprandial glucose is important in the management of diabetes. Our recent research showed that benzylidene indanone derivative 2-(3,4-dihydroxybenzylidene)-4-methoxy-2,3-dihydro-1H-inden-1-one (2-BI) showed antihyperglycemic activity, but its role in glucose homeostasis in the liver is unknown. 1H NMR metabolomics approach was used to unravel the effectiveness of 2-BI, on hepatic glucose production in fructose-streptozotocin (STZ) diabetics. Diabetes was induced in Sprague–Dawley rats using fructose-streptozotocin. Metabolites were extracted from the liver tissue and analyzed by 1H NMR spectroscopy. Pathway analysis was performed on the identified metabolites. The unsupervised principal components analysis score plot showed clear differentiation. The control group (NC) was clearly separated from the diabetic group (DBC) and was clustered near the treated diabetic groups (DBI and DGT). There is a significant (p < 0.01) increased level of 12 metabolites in diabetes rats that are crucial in liver glucose homeostasis. Treatment with 2-BI was able to lower the level of these metabolites. Detailed pathway analysis of the spiked metabolite levels shows an effect on the glycolysis/gluconeogenesis, butanoate, amino acid, nitrogen, and nucleotide (pyrimidine) metabolism. 2-BI reduced hyperglycemia in diabetic rats via the attenuation of hepatic glucose production and advancement of liver insulin sensitivity.

Antidiabetic Effect of Combined Leaf Extracts of Portulaca oleracea L., Beta vulgaris L., and Cichorium intybus L. in Streptozotocin-Induced Diabetic Rats.

Purslane (P), chard (CHA), and chicory (CHI) leaf extracts are individually and traditionally used in the treatment of diabetes mellitus. Polyphenols, flavonoids, the polyphenolic profile of the extracts, and their antioxidant activity were determined. This study evaluated the antidiabetic activity of combinations of these extracts in streptozotocin-induced diabetic rats. Diabetic groups were administered orally and daily for 40 days with the investigated extracts at 250 mg/kg body weight (b.w.) or metformin (100 mg/kg b.w.) as a drug. Fasting blood glucose, oral glucose tolerance, insulin, and fructosamine were assessed. The combined extracts with high levels of P or CHI exerted potent hypoglycemic activity compared with metformin in addition to the restoration of the histopathological changes in the liver and pancreas of diabetic rats to a near-normal state. Therefore, these combined extracts could be developed as natural drugs for diabetes.

SAT072 Choline Deprivation Aggravates Hyperglycemia And Fatty Liver In Non-obese Streptozocin-induced Diabetic Rats

Abstract Disclosure: C. Liapi: None. A. Kyriakaki: None. H. Al Humadi: None. R. Al-Saigh1: None. A. Al Humadi: None. A. Lazaris: None. Background: Choline deprivation (CD) is an established model of steatohepatitis. There is a strong association between non-alcoholic fatty liver disease and diabetes mellitus that has a significant impact on the global health system. The combined state of CD and diabetes can resemble common cases in clinical practice including parenteral nutrition, pregnancy, chronic liver disease malnutrition and/ or alcoholism in diabetic individuals. The aim of this study was to investigate the effects of choline deprivation on glycemic control, insulin signaling pathway and lipid metabolism in non-obese streptozocin-induced diabetic rats. Methods: Thirty-two male adult Wistar rats were divided into four groups; control, diabetes (DM), choline-deprived diet (CDD), and combined group (DM+CDD); DM was induced by intraperitoneal streptozotocin administration. Body weight, fasting blood glucose and plasma insulin levels, lipid profile, liver biochemistry, liver histopathology and gene expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), glucose transporters 2 &amp; 4 (GLUT-2 &amp; -4) in hepatic tissue, were assessed. Results: The combination group (CDD+DM) showed a significant increase in blood glucose associated with a significant decrease in plasma insulin level and evidence of dyslipidemia with a significant increase in liver enzymes, histopathology showed extensive micro- and macrovesicular steatosis and a significant decrease in weight gain versus the control, CDD and DM group. A significant increase was observed in gene expression of IR, IRS-1, GLUT-2, and GLUT-4 in all the experimental groups versus the control. Conclusion: The combination of choline deficiency and diabetes has drawn some new scenarios on insulin and some hepatic metabolic pathways: (i) plasma insulin resistance with progressive hyperglycemia and hyperlipidemia.(ii) attenuation of hepatic insulin resistance or sensitization of insulin signaling pathways in the liver, due to the hepatotoxic effects of choline deficiency that could ultimately simulate features of the metabolic syndrome, and (iii) experimentally simulation of metabolic conditions seem to act synergistically, leading to poor glycemic control along with aggravation of hepatic steatosis. Presentation: Saturday, June 17, 2023

Gastroprotective evaluation of Medicago sativa L. (Fabaceae) on diabetic rats

Traditional uses for the plant Medicago sativa (M. sativa) (Alfalfa) (Family: Fabaceae) include liver protection, antioxidant activity, and the treatment of bleeding and digestive issues. This study aims to assess the effect of ethanol extract of M. sativa (EEMS) on experimental-induced ulcers in diabetic rats. By pylorus ligation and ethanol administration, gastric ulcers were induced in diabetic rats. Five groups each consisting of six rats in each model were used. All other groups except Group I were made diabetic by giving rats alloxan (140 mg/kg i.p.). Vehicles were given to Group I (normal control) and Group II (diabetes control) rats. Group III (positive control) received ranitidine 50 mg/kg, and Group IV and V received EEMS at doses of 100 and 400 mg/kg, respectively. In the pylorus ligation and ethanol-induced stomach ulcer model of rats, the findings demonstrated that EEMS (100 mg/kg) showed a decreased ulcer index of 2.01 ± 0.41 and was found statistically significant against the diabetes control group (p < 0.001) as well as, an ulcer index of 0.68 ± 0.22 by EEMS (400 mg/kg) with a significant reduction in the ulcer index (p < 0.001). EEMS (100 and 400 mg/kg) reduce free acidity by 13.16 ± 0.65 mEq/L and 9.83 ± 0.30 mEq/L, respectively. EEMS also showed a protective impact on the liver and kidneys of diabetic rats. Antihyperglycemic action was also discovered in diabetic animals. The findings of the current investigation demonstrated that ethanolic extract of M. sativa possesses anti-ulcer activity in diabetic rats. Ethanolic extract of M. sativa may be a treatment option for stomach ulcers that also have diabetes.

The Potential Hepatoprotective Effect of Vaccinium arctostaphylos L. Fruit Extract in Diabetic Rat.

Vaccinium arctostaphylos has traditionally been employed in Iranian folk medicine to treat diabetes. However, the precise molecular mechanisms underlying its antidiabetic properties remain incompletely understood. The current experiment intended to explore the modulatory effects of V. arctostaphylos fruit ethanolic extract (VAE) on biochemical and molecular events in the livers of diabetic rats. In this experimental study, male Wistar rats were randomly assigned to four groups: normal control, normal rats with VAE treatment, diabetic control, and diabetic rats with VAE treatment. Following 42 days of treatment, the impact of VAE on diabetes-induced rats was assessed by measuring various serum biochemical parameters, including insulin, free fatty acids (FFA), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), and adiponectin levels. The activities of hepatic carbohydrate metabolic enzymes and glycogen content were determined. Additionally, expression levels of selected genes implicated in carbohydrate/lipid metabolism and miR-27b expression were evaluated. H and E-stained liver sections were prepared for light microscopy examination. Treatment with VAE elevated levels of insulin and adiponectin that reduced levels of FFA, ROS, and TNF-α in the serum of diabetic rats. VAE-treated rats exhibited increased activities of hepatic glucokinase (GK), glucose-6-phosphate dehydrogenase (G6PD), and glycogen concentrations, in conjunction with decreased activities of glucose-6-phosphatase (G6Pase) and fructose-1,6-bisphosphatase (FBPase). Furthermore, VAE significantly upregulated the transcription levels of hepatic insulin receptor substrate 1 (Irs1) and glucose transporter 2 (Glut2), while considerably downregulated the expression of peroxisome proliferator-activated receptor gamma (Pparg) and sterol regulatory element-binding protein 1c (Srebp1c). VAE remarkably enhanced the expression of miR27-b in the hepatic tissues of diabetic rats. Abnormal histological signs were dramatically normalized in diabetic rats receiving VAE compared to those in the diabetic control group. Our findings underscore the hypoglycemic and hypolipidemic activities of V. arctostaphylos and assist in better comprehension of its antidiabetic properties.

Melatonin and probiotic administration ameliorated hyperglycaemia, oxidative stress, and enhanced cytoprotective effect on beta-cells of diabetic rats.

The study aimed at investigating the effects of administering melatonin and a probiotic to streptozotocin-induced diabetic rats on hyperglycaemia, oxidative stress biomarkers and beta-cells. Type 1 diabetes was induced in 5 months-old male Wistar rats by single intraperitoneal (i.p.) administration of freshly-prepared STZ (60mg/kg body weight). Six groups of 10 rats were used and treated once daily for six weeks; (1) Healthy control: normal saline only; (2) Pre-treated with Melatonin (MEL); (3) Diabetic control; (4) Diabetic + Treated with MEL; (5) Diabetic + Treated with Probiotic (Prob); (6) Diabetic + Treated with MEL + Prob. Blood glucose, body weight, activities of antioxidant enzymes and malondialdehyde concentration in serum and tissues, reduced glutathione and immunohistochemical assay. Data obtained were expressed as mean ± standard error of the mean (Mean ± SEM) and subjected to ANOVA followed by Tukey's post hoc test. Melatonin + Probiotic significantly decreased blood glucose concentrations in diabetic treated rats, compared to the diabetic control rats. MEL + Probiotic increased (p < 0.05) superoxide dismutase activity in serum and liver of diabetic rats. MEL + Probiotic reduced (p < 0.05) malondialdehyde concentration in the serum, liver and kidneys, respectively. MEL + Probiotic treated diabetic rats displayed islets with much greater content of insulin. Melatonin + Probiotic combination was more effective in mitigating hyperglycaemia, oxidative stress, and exerted cytoprotective effect on the beta-cells.

Antihyperglycemic and Histological Effect of Aloe vera on Alloxan-Induced Diabetes in Wistar Rats

Introduction: Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia and is associated with various complications if not properly managed. Aloe vera, a medicinal plant with diverse pharmacological properties, has shown promise as a potential therapeutic intervention for diabetes. This study aimed to investigate the antihyperglycemic and histological effects of Aloe vera in an alloxan-induced diabetic Wistar rat model. Method: Forty-eight Wistar rats were divided into six groups and treated with different regimens of Aloe vera and metformin, a standard antidiabetic drug. The effects of the treatments on blood glucose levels and histology of the pancreas, liver, and kidney were evaluated. Result: The results of the study revealed that alloxan injection induced hyperglycemia and pathological changes in the pancreas, liver and kidney of Wistar rats. The treatment with 100mg/kg, 200mg/kg and 400mg/kg of Aloe vera significantly reduced blood glucose levels in a dose-dependent manner. Additionally, Aloe vera administration preserved the histological integrity of the pancreas, liver, and kidney in diabetic rats. This preservation of organ histology can be attributed to the antioxidant, anti-inflammatory, and tissue-protective properties of Aloe vera. Conclusion: Aloe vera demonstrated antihyperglycemic effects and preserved organ histology in an alloxan-induced diabetic Wistar rat model. The bioactive compounds present in Aloe vera are believed to contribute to these effects. Aloe vera holds potential as an alternative or adjunctive therapy for diabetes management, but its clinical efficacy and safety need to be further explored.

Effect of Hydroxytyrosol on Prdx6 Expression in Diabetic Rat Liver

Aim: Oxidative stress caused by hyperglycemia, which is the most important complication of diabetes mellitus, causes liver damage. Hydroxytyrosol is a polyphenolic compound abundant in olive oil that protects the liver against oxidative damage. Peroxiredoxin 6 (Prdx6) is an anti-oxidative enzyme known to exist in the liver. The aim of this study was to investigate the effect of hydroxytyrosol on Prdx6 expression in diabetes-induced liver injury.&#x0D; Material and Methods: Male Wistar rats were grouped into four as the control group (n=10), hydroxytyrosol group (n=10), streptozotocin group (n=10), and hydroxytyrosol+streptozotocin group (n=10). Blood glucose levels of the animals were measured after streptozotocin injection and at the end of the experiment. The general structure of the liver was examined with a hematoxylin-eosin stain. Prdx6 protein expression was determined with an immunohistochemical method.&#x0D; Results: In the streptozotocin+hydroxytyrosol group, blood glucose level was found to be lower when compared with the streptozotocin group (p

Effects of Caraway and (S)-(+)-carvone Extract on the Expression of Genes Coding Key Glycolytic Enzymes in Streptozotocin-induced Diabetic Rats

Background: Diabetes mellitus is a metabolic disorder causing dysfunctional regulation of carbohydrate metabolism and contributing to multiple serious health challenges worldwide. Aims: This research explores the effect of caraway hydroalcoholic extract and (S)-(+)-carvone on the transcription of genes coding for key glycolytic enzymes in the liver of the diabetic rat treated with streptozotocin (STZ). Methods: In this experimental study, diabetes was established in four groups of rats by injecting 45 mg/kg of STZ intraperitoneally. Further normal rats that were not injected formed the control group. Over four weeks, the effects of caraway hydroalcoholic extract (150 and 250 mg/kg) and carvone (100 mg/kg) were evaluated using PCR and histopathological evaluation, specifically in the form of effects on the transcription process of genes coding key glycolytic enzymes in the liver of the diabetic rats. Results: Over the four-week assessment period, rats’ food intake, and therefore blood glucose levels, were decreased through the daily oral administration of carvone and caraway extract (150 mg/kg) when compared to those administered with further STZ. The expression of key glycolytic enzymes, including glucokinase, pyruvate kinase, and phosphofructokinase 1 in the liver of diabetic rats was restored to near-normal levels by carvone and caraway extract, especially at the 150 mg/kg dose. Histopathological evaluation of diabetic rat liver demonstrated that administration of caraway extract and carvone decreased the STZ-induced damage to liver tissue. Conclusion: 150 mg/kg of caraway extract strongly regulates glycolysis by regulating the gene expression of key glycolytic enzymes in diabetic rats.