Liver Of Diabetic Rats Research Articles

Cola Nitida (Kola Nuts) Attenuates Hepatic Injury in Type 2 Diabetes by Improving Antioxidant and Cholinergic Dysfunctions and Dysregulated Lipid Metabolism.

The therapeutic effect of Cola nitida hot infusion against diabetes hepatic injury was investigated in livers of diabetic rats. Cola nitida was infused in boiling water and concentrated. The concentrated infusion was administered to T2D rats at low and high doses (150 and 300 mg/kg body weight (bw), respectively). The normal group (positive control) and another diabetic group (negative control) were administered distilled water, while metformin served as the standard drug. A toxic group that consists of normal rats administered a high dose of C. nitida. After 6 weeks, the rats were sacrificed, and their livers were collected. They were assayed for oxidative stress markers, myeloperoxidase, acetylcholinesterase and ATPase activities. Hepatic lipid metabolites were profiled with GC-MS and their metabolic pathways were analyzed using the MetaboAnalyst 4.0 online server. Treatment with C. nitida caused a significant elevation of glutathione level and SOD activity, while concomitantly inhibiting lipid peroxidation, myeloperoxidase, acetylcholinesterase and ATPase activities in hepatic tissues of the rats. Treatment with C. nitida also caused significant depletion of diabetes-generated lipid metabolites, with concomitant generation of fatty esters and steroids as well as inactivation of diabetes-activated pathways. These data demonstrate the therapeutic effect of C. nitida against diabetic hepatotoxicity in diabetic rats.

Nicotinamide and heat preconditioning - Effects on hepatic HSP70, carbohydrate and oxidative disturbances in STZ-induced diabetic rats.

Nicotinamide (NA) is known to have antioxidant potential and partially to protect insulin-secreting cells against diabetogenic agent STZ (streptozotocin). In a combination to heat stress (HS), NA is also known to induce heat-shock proteins (HSPs) production. Heat preconditioning (HP) and HSPs have cytoprotective effects against development of cellular injury caused by application of subsequent stressor. We aimed to determine if pretreatment with NA and HP (as HSP70 -inducers) can affect STZ-induced diabetic disturbances in rats. NA-pretreatment (250mg/kg b.w., 7 days) and heat preconditioning (41±1°C, 45min) of diabetic rats was performed. The changes in hepatic carbohydrate- and antioxidative-related enzymes and substrates were investigated. NA-pretreatment, alone or in combination with HS, resulted in significant increase of HSP70 concentration in the liver of control and diabetic rats. Compared to diabetic controls, pretreatment with NA, in combination with HP, resulted in decrease of blood and liver glucose, increase of glycogen and glucose-6-phosphate level, increase of glycogenolytic/glycolytic enzymes, decrease of gluconeogenic enzymes, as well as an increase of glutathione content and glutathione peroxidase, decrease of glutathione reductase and catalase activities. NA is a potent HSP70 coinducer, alone or in a combination with HS in the liver of both control and diabetic rats. Pretreatment with NA, accompanied by HP, has a pronounced corrective effect on STZ-induced diabetes disturbances in the key hepatic carbohydrate- and antioxidative-related parameters. It seems that this corrective effect is based on the increased production of hepatic HSP70.

CTRP13 attenuates the expression of LN and CAV-1 Induced by high glucose via CaMKKβ/AMPK pathway in rLSECs.

Objective: To investigate the effect and mechanism of CTRP13 on hepatic sinusoidal capillarization induced by high glucose in rat liver sinusoidal endothelial cells (rLSECs).Results: CTRP13 was reduced in high glucose-treated rLSECs. High glucose increased LN and CAV-1 expression and inhibited CaMKKβ and AMPK phosphorylation. CTRP13 overexpression protected rLSECs against high glucose-induced increase of LN and CAV-1 expression. Moreover, CTRP13 overexpression increased high glucose-induced inhibition of CaMKKβ and AMPK activation in CTRP13-overexpressing rLSECs. Inhibition of CaMKKβ and AMPK disturbed the protective effects of CTRP13 in high glucose-induced increase of LN and CAV-1. Hepatic steatosis was enhanced and basement membrane was thickened in liver of diabetic fatty liver rats.Conclusions: Our data identified the protective role of CTRP13 in hepatic sinusoidal capillarization induced by high glucose via activating CAMKKβ/AMPK pathway. CTRP13 may be a potential target for screening and treating diabetic fatty liver.Methods: Construct lentiviral CTRP13 overexpression vector and transfect rLSECs. Use STO-609 (a CaMKKβ inhibitor) or Compound C (an AMPK inhibitor) to treat rLSECs. CTRP13, CaMKKβ, AMPK, laminin (LN) and caveolin-1 (CAV-1) were detected by qRT-PCR and Western blotting. Establish rat model of diabetic fatty liver. Use immunohistochemistry, hematoxylin-eosin and silver staining to observe the histopathological features of liver.

Arctium lappa L. polysaccharide can regulate lipid metabolism in type 2 diabetic rats through the SREBP-1/SCD-1 axis

In the analysis of risk factors of diabetes mellitus with coronary heart disease, dyslipidemia is the most important. Previous studies have found that Arctium lappa L. polysaccharide (ALP) can regulate lipid metabolism in type 1 diabetic rats, but it has not been studied in type 2 diabetes. In this study, the regulatory effect of ALP on lipid metabolism in type 2 diabetic rats was investigated by constructing a model of type 2 diabetes. The results of blood biochemical analysis showed that ALP effectively reduced the synthesis of triglycerides and cholesterol, and reduced the risk of atherosclerosis in diabetic rats. Histopathological observation (hematoxylin and eosin, Masson, Periodic Acid-Schiff and oil red O staining) showed that it also effectively regulated lipid metabolism in the liver of diabetic rats and inhibited the process of liver fibrosis. Immunohistochemistry and Western blot analysis showed that ALP regulated the expression of sterol regulatory element-binding protein-1 (SREBP-1) and stearoyl-CoA desaturase 1 (SCD-1) in the liver of diabetic rats. In conclusion, the results of this study demonstrate that ALP can effectively regulate lipid metabolism and reduce the risk of atherosclerosis in type 2 diabetic rats through the SREBP-1/SCD-1 axis.

Promotion of Adropin Expression by Hyperglycemia Is Associated with STAT3 Activation in Diabetic Rats.

BackgroundAdropin is a secreted polypeptide that has been demonstrated to play an important role in energy homeostasis and lipid metabolism. Signal transducer and activator of transcription 3 (STAT3) may promote the transcription of target genes including adropin. In the current study, we investigated the effect of adropin on glucose metabolism in diabetic rats and the mechanism that governs this effect was subsequently assessed.Materials and MethodsRats received a single injection of streptozotocin to induce type 1 diabetes. The diabetic rats were treated with insulin or phloridzin, another antidiabetic agent through inhibition of glucose reabsorption, for 7 days. Plasma glucose levels and adropin levels were measured. The interaction between STAT3 and adropin was evaluated using the human hepatoma HepG2 cell line. HepG2 cells were pretreated with the specific antagonist Stattic or with STAT3-specific siRNAs to knockout STAT3. Changes in energy homeostasis-associated gene expression were measured using real-time PCR. The protein expression levels of pSTAT3 and STAT3 were measured using Western blotting.ResultsIn diabetic rats, the serum concentrations of adropin were increased in the vehicle-treated group and decreased in the insulin- or phloridzin-treated group. In liver tissues, the Enho expression level and the activity of STAT3 also showed similar tendencies. After HepG2 cells were treated with medium containing high glucose, the ratio of p-STAT3 to STAT3, Enho mRNA levels and reactive oxygen species expression levels in HepG2 cells were significantly increased in conjunction with increased glucose levels. The effect was inhibited after pretreatment with Stattic or knockdown with STAT3-specific siRNAs.ConclusionSTAT3 is involved in the genetic regulation of adropin, increasing the levels of circulating adropin and promoting Enho expression in the livers of diabetic rats.

Extraction of Phenolic Compounds from Tabernaemontana catharinensis Leaves and Their Effect on Oxidative Stress Markers in Diabetic Rats.

The aim of this study was to evaluate the most effective extraction condition (temperature, solvent type and time) for recovery of high-value phytochemicals present in the Tabernaemontana catharinensis leaves (TC) and to assess their effect on biochemical parameters in streptozotocin-induced diabetic rats. The extraction of phenolic compounds from TC using a factorial design (FD) 2³, high performance liquid chromatography (HPLC), response surface methodology (RSM) and principal component analysis (PCA) were studied. It was found that the optimal conditions for extraction of phenolics were higher temperature (65 °C) and time (60 min) using ethanol as extractor solvent. In this condition of extraction (A8), total phenolic compounds (TPC) and antioxidant activity (AA) were determined. Additionally, this extract was used to evaluate their effect on antioxidant enzyme activities (superoxide dismutase (SOD) and catalase (CAT)) as well as lipid peroxidation (LP) and protein thiols level (PSH) in the liver and kidneys of normal and diabetic rats. As result, T. catharinensis extract presented TPC content of 23.34 mg EAG/g (equivalent gallic acid) and AA of 34.26 μmol Trolox/g. Phenolic acids (ferulic acid and coumaric acid) and flavonoids (quercetin, rutin and pinocembrin) could be recovered and identified by HPLC. This study indicated an important role of the T. catharinensis extract on free radical inactivation and on the antioxidant defense system in diabetic rats. In fact, the use of T. catharinensis extract restored the normal activity of SOD (p < 0.05) and suppressed malondialdehyde levels in liver and kidney tissues. Thus, the T. catharinensis extract, rich in phenolic compounds, can be responsible for the recover the enzymatic changes in the liver and kidney tissues provoked by diabetes in rats. In addition, the lipid peroxidation rate decreased in the diabetic rats treated with T. catharinensis.

Curcumin, Alone or in Combination with Aminoguanidine, Increases Antioxidant Defenses and Glycation Product Detoxification in Streptozotocin-Diabetic Rats: A Therapeutic Strategy to Mitigate Glycoxidative Stress.

Both oxidative stress and the exacerbated generation of advanced glycation end products (AGEs) have crucial roles in the onset and progression of diabetic complications. Curcumin has antioxidant and antidiabetic properties; its combination with compounds capable of preventing the advanced glycation events, such as aminoguanidine, is an interesting therapeutic option to counteract diabetic complications. This study is aimed at investigating the effects of treatments with curcumin or aminoguanidine, alone or in combination, on metabolic alterations in streptozotocin-diabetic rats; the focus was mainly on the potential of these bioactive compounds to oppose the glycoxidative stress. Curcumin (90 mg/kg) or aminoguanidine (50 and 100 mg/kg), alone or in combination, slightly decreased glycemia and the biomarkers of early protein glycation, but markedly decreased AGE levels (biomarkers of advanced glycation) and oxidative damage biomarkers in the plasma, liver, and kidney of diabetic rats. Some novel insights about the in vivo effects of these bioactive compounds are centered on the triggering of cytoprotective machinery. The treatments with curcumin and/or aminoguanidine increased the activities of the antioxidant enzymes (paraoxonase 1, superoxide dismutase, and catalase) and the levels of AGE detoxification system components (AGE-R1 receptor and glyoxalase 1). In addition, combination therapy between curcumin and aminoguanidine effectively prevented dyslipidemia in diabetic rats. These findings demonstrate the combination of curcumin (natural antioxidant) and aminoguanidine (prototype therapeutic agent with anti-AGE activity) as a potential complementary therapeutic option for use with antihyperglycemic agents, which may aggregate beneficial effects against diabetic complications.

Effects of Hydroalcoholic Leaf Extract of Avicennia marina on Apoptotic, Inflammatory, Oxidative Stress, and Lipid Peroxidation Indices and Liver Histology of Type 1 Diabetic Rats

Background: Avicennia marina (A. marina) has been traditionally used in the treatment of various diseases due to its anti-inflammatory and antioxidant properties. Objectives: The study aimed to determine the effect of hydroalcoholic leaf extract of A. marina on apoptotic, inflammatory, oxidative stress, and lipid peroxidation indices and liver histology of type 1 diabetic rats. Methods: In this laboratory research, a total of 40 male Wistar rats were randomly divided into five groups including the control group, type 1 diabetes mellitus (DM) group, diabetic group receiving 50 mg/kg of hydroalcoholic extract of A. marina, diabetic group receiving 100 mg/kg of A. marina, and the diabetic group receiving 200 mg/kg of A. marina. The control and DM groups were intraperitoneally administered with 0.5 mL of saline solution as the solvent for 30 days. The experimental groups were intraperitoneally administered with 0.5 mL of hydroalcoholic extract at doses of 50, 100, and 200 mg/kg for 30 days, respectively. Diabetes mellitus was induced by an intraperitoneal injection of 120 mg/kg of alloxan monohydrate. At the end of treatment, we measured the serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6. Also, we assessed the levels of BCL2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), caspase-9, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), and 8-hydroxy-2’-deoxyguanosine (HOdG-8) using ELISA in liver tissues. Histological changes in the liver were also investigated. Results: The levels of Bcl-2, SOD, CAT, and GPx were significantly higher in the experimental groups receiving 100 and 200 mg/kg of A. marina in a dose-dependent manner than in the DM group. The levels of Bax, caspase-9, MDA, and HOdG-8 were significantly lower in the experimental groups in a dose-dependent manner. Also, the serum levels of TNF-α, IL-1β, and IL-6 were significantly lower in these groups in a dose-dependent manner (P 0.05). The results showed that A. marina extract improved the histological changes in the liver of diabetic rats in a dose-dependent manner. Conclusions: The administration of the hydroalcoholic extract of A. marina can improve liver tissue damage and reduce diabetes-related liver complications by decreasing apoptosis, inflammation, oxidative stress, and lipid peroxidation.

NLRP3 inflammasome drives inflammation in high fructose fed diabetic rat liver: Effect of resveratrol and metformin

AimsTo unravel the underlying mechanism of hepatic inflammation during type 2 diabetes (T2DM), we established the diabetic rat model by feeding with high fructose diet for twenty weeks and studied the involvement of inflammasome in the liver of these rats. Materials and methodsMale SD rats weighing 180–200 g were divided in four groups: 1) Control (Con group) rats were fed with corn starch diet, 2) diabetic (Dia group) rats were fed with 65% of fructose, 3) diabetic along with resveratrol (10 mg/kg/day); p.o. (Dia + Resv group) and 4) diabetic along with metformin (300 mg/kg/day); p.o. (Dia + Met group), for twenty weeks. We evaluated the establishment of T2DM in fructose fed rats and the effect of resveratrol and metformin treatment on different diabetic parameters in these rats. Further we investigated the role of NLRP3 inflammasome on T2DM induced liver inflammation and effect of resveratrol and metformin treatment on NLRP3 inflammasome driven inflammatory response. Key findingsRats from Dia group; manifested insulin resistance, hyperinsulinemia, hyperglycemia, elevated uric acid along with hypertriglyceridemia after fructose feeding for twenty weeks. Mostly, above parameters were attenuated in resveratrol and metformin treated groups. Expression of NLRP3 inflammasome components in liver were increased in Dia group rats with elevated transcript levels of pro-inflammatory cytokines. Histopathological examination revealed increase in glycogen content and fibrosis in Dia group rats; which was considerably reduced with resveratrol and metformin treatment. SignificanceOur study suggests that management of inflammation may be considered as an alternative approach to prevent liver tissue injury during chronic diabetic condition.

The Effect of Aqueous Extract of Pine Kindling on the Liver and Kidney Tissues of Diabetic Rats

This study aimed to investigate the effect of aqueous extracts from the obtained kindling wood of pine trees on liver and kidney tissues in diabetes induced by streptozotocin in rats. Male Sprague Dawley rats were divided into five groups: 1) Controls, 2) STZ rats 3) STZ rats treated with aqueous extracts from the obtained kindling wood of pine trees (different doses) for 10 weeks. According to our results, it was determined that these extracts show beneficial effects on oxidative stress in liver and kidney tissues. In vitro studies, bovine, porcine pancreas, fungi and bacteria derived from amylase on enzyme activity of the pine extracts haven’t been observed the inhibitory effect. Also disaccharides α-glycosidase enzyme that hydrolyzes on kindling of the pine was found to not have an inhibitory effect.

Farrerol ameliorates diabetic hepatopathy in rat model of type 2 diabetes mellitus via modulation of oxidativeinflammatory stress

Purpose: To investigate the effect of farrerol on diabetic hepatopathy in a rat model of type 2 diabetes mellitus (T2DM).Methods: Adult male Wistar rats (n = 40) were randomly assigned to four groups of ten rats each: normal control, diabetic control, farrerol control and treatment groups. With the exception of normal control and farrerol control groups, the rats were fed high-fat diet (HFD) for four weeks, and thereafter injected streptozotocin (STZ) at a dose of 30 mg/kg body weight intraperitoneally (i.p.) for induction of T2DM. Rats in farrerol control and treatment groups received 50 mg/kg farrerol orally/day. Serum levels of triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and lowdensity lipoprotein cholesterol (LDL-C) were determined. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were assessed in liver homogenate while mRNA and protein expressions of glucose transporter 2 (GLUT2) were assayed in liver using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also determined using qRT-PCR.Results: Diabetes mellitus (DM) led to significant reductions in rat body weight and SOD activity, while increasing fasting blood glucose (FBG) and MDA levels (p &lt; 0.05). However, treatment with farrerol significantly reversed the effect of DM on these parameters (p &lt; 0.05). The mRNA expressions of TNF-α and IL-1β were significantly higher in diabetic control group than in normal control group, but were significantly reduced after farrerol treatment (p &lt; 0.05). Treatment with farrerol also significantly reversed the effect of DM on rat lipid profile (p &lt; 0.05). The expression of GLUT2 protein was significantly downregulated in the liver of diabetic control rats, when compared with normal control rats, but was significantly upregulated after treatment with farrerol (p &lt; 0.05).Conclusion: The results of this study show that farrerol alleviates STZ-induced hyperglycemia and dyslipidemia via reduction in oxidative stress and inflammation, and upregulation of GLUT2 protein expression. Thus, farrerol has antidiabetic and hepatoprotective potentials for clinical use in humans.&#x0D; Keywords: Diabetes mellitus, Dyslipidemia, Farrerol, Hepatopathy, High-fat diet

In vitro and in vivo Antioxidant Properties of Extracts from the Root of Curcuma longa Linn

Many plants possess antioxidants that exhibit additive or synergistic activities. The antioxidant activities of the root of Curcuma longa Linn extracts extracted different solvents were investigated by using several established in vitro systems: α,α-diphenyl-β-picrylhydrazyl (DPPH) radical scavenging activity, hydrogen Peroxide scavenging activity (HPSA), nitric oxide radical scavenging activity (NOSA) and ferric reducing antioxidant power (FRAP). The result showed that methanol extract exhibited greater antioxidant activity in vitro which was statistically significant compared to the other extracts. Based on the in vitro results, the methanol extract was subjected to column chromatography. Six pooled fractions (FI-FVI) were evaluated for in vivo antioxidant activity in liver and kidney of alloxan-induced diabetic rats using a total of forty-five (45) rats which were grouped into nine (9) groups of five (5) rats. The in vivo antioxidants showed a significant decrease in superoxide dismutase (SOD), catalase (CAT) and gluthatione peroxidase (GPx) levels in both liver and kidney of Alloxan-induced diabetic rats. These changes were significantly reversed after treatment with methanol fraction II and the standard drug. Thus, Curcuma longa Linn may be useful in the management of diabetes and oxidative stress.

Antioxidant activity of the ethyl acetate extract of Justicia spicigera in two periods of the year (spring‐summer and autumn‐winter) in the liver of adult diabetic rats

BackgroundDiabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. In studies it was shown that the ethanol extract of Justicia spicigera has a hypoglycemic effect in streptozotocin‐induced rats (STZ), related to the presence of secondary metabolites, such as kaempferitrin. However, the concentration of these compounds presents drastic variations under different environmental conditions.ObjectiveThe objective of this project is to study the activity of secondary metabolites produced by Justicia spicigeraduring two periods of the year (spring‐summer and autumn‐winter) in a chronic diabetes model on the liver of streptozotocin‐induced rats.MethodsMale Wistar rats (450–500 g) with 20 weeks of age were used, divided into 6 groups: normoglycemic control (CN) and diabetic (CD), administered with spring‐summer extract (NEPV and DEPV) and autumn‐winter ( NEOI and DEOI) for 60 days, diabetic rats were induced with an intraperitoneal injection of STZ (45 mg / kg). During treatment the weight and blood glucose were determined every 6 days. Subsequently, the rats were submitting euthanasia to obtain weight, homogenate and mitochondria of liver, which were used for the determination of catalase and superoxide dismutase activities and glutathione levels.ResultsThe ethyl acetate extract of Justicia Spicigera collected during the spring‐summer season significantly lowers blood glucose levels and prevents excessive loss of body weight and liver growth increases catalase activity and reduced glutathione levels. The ethyl acetate extract of Justicia Spicigera collected during the autumn‐winter season prevents excessive loss of body weight and liver growth, but does not exhibit antioxidant activity when compared to the DEPV group.In conclusion, the concentration of Justice spicigera compounds related to hypoglycemic and antioxidant activity is affected by environmental factors.Support or Funding InformationThe authors appreciate the partial economic support from CIC‐UMSNH (2.16, to ASM).

Hepatic- and Renal protective Effects of Chrysophyllum albidum (African Star Apple) Fruit-Skin Supplementation on Streptozotocin-Induced Diabetic Rats

Chrysophyllum albidum commonly called African star apple, has been reported for its antidiabetic potential but its effect on liver and kidney functions in diabetic rats has not been well investigated. This study investigated effects of Chrysophyllum albidum fruit-skin (CAFS) supplemented diet on Streptozotocin-induced diabetic rats. Diabetes was induced intraperitonealy at a single dose of 50mg/kg bw of Streptozotocin (STZ). Forty male Wistar rats weighing averagely 170g were randomly divided into four groups of ten rats each; Group 1-Normal control, Group 2-Diabetic control, Group 3-Diabetic rats treated Glibenclamide, Group 4-Diabetic rats treated 70g/kg CAFS supplemented diet. After four weeks of treatment, the rats were sacrificed. Liver function biomarkers (Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Alkaline phosphatase (ALP)) activities, kidney function biomarkers (Creatinine and Urea), electrolyte ions (K + , Na + , HCO 3 - and Cl - ), total protein and bilirubin levels were measured in the plasma. The diabetic control exhibited hepato-renal dysfunction with significant (p&lt;0.05) increase in the liver marker enzymes’ activities, total bilirubin, creatinine and urea concentrations while decreasing total protein, albumin and electrolyte ions levels compared with normal control group. Treatment with CAFS supplemented diet significantly (p&lt;0.05) enhanced liver and kidney recovery by reducing the elevated activities of liver marker enzymes, reversed the increments in creatinine, urea and total bilirubin while increasing the concentration of total protein and restoring electrolyte ions concentrations to near normal values. CAFS supplemented diet has hepatic- and renal protective effects on STZ-induced diabetic rats. Thus, CAFS could be considered as therapeutic agent against the progression of diabetes complications. Keywords: Chrysophyllum albidum ; fruit-skin; liver markers; kidney markers; diabetes. DOI: 10.7176/JNSR/10-6-02 Publication date: March 31 st 2020

Launaea taraxacifolia leaf partitions ameliorate alloxan-induced pathophysiological complications via antioxidant mechanisms in diabetic rats

Launaea taraxacifolia (Wild.) Amin ex. Jeffery belongs to family Asteracaea. The plant is used for treatment of diseases and eaten as vegetable in Nigeria. This study investigated the ameliorative potentials of L. taraxacifolia leaf partitions in alloxan induced diabetic complications. Male Albino rats were divided into eleven groups of five rats each. Diabetes was induced following intraperitoneal administration of 150 mg/kg alloxan monohydrate and was treated with 200 and 300 mg/kg of each partitioned fractions. Hyperglycemia was reversed in all treated rats within seven days of treatments. Rats treated with the partitions showed significant increase in hematological parameters compared with diabetic control. N-hexane fraction had the best overall effect against oxidative stress particularly on heart and pancreas reduced glutathione (GSH), superoxide dismutase (SOD) and kidney glutathione S-transferase (GST) activities. The various degrees of degeneration observed in the kidney, liver, pancreas and heart of the untreated diabetic rats were milder in rats treated with partitions. The results therefore revealed the ameliorative potentials of the partitioned fractions of L. taraxacifolia leaf extract against diabetes mellitus complications via activation of the antioxidant enzymes.

MDA levels in the pancreas, testes, liver, and plasma of diabetic rats: The effect of snakehead (Channa striata) extract

Abstract. Abdulgani N, Hidayati D, Adinovitasary R, Oliviatie V, Sekartaji AD. 2020. MDA levels in the pancreas, testes, liver, and plasma of diabetic rats: The effect of snakehead (Channa striata) extract. Nusantara Bioscience 12: 50-54. There are several biomarkers of oxidative stress in diabetes mellitus; one of those biomarkers is Malondialdehyde (MDA). Increasing oxidative stress will cause increased tissue damage. This study was conducted to determine the effect of snakehead extract (SHE) on MDA level of pancreas, testes, liver, and plasma of alloxan-induced diabetic rats. There were 5 groups of treatments: non-diabetic rats/negative control (C-), diabetic rats/positive control (C+), and 3 SHE level of administration: 1 mL/day (low dose/LD), 1.6 mL/day (middle dose/MD) and 2.1 mL/day (high dose/HD). Alloxan-induced diabetic rats were administered with SHE extract orally every day for two weeks. The results showed that MDA levels in the testes, liver, pancreas, and plasma of diabetic rats administered with SHE and non-diabetic rats/negative controls (C-) were significantly lower (p &lt;0.05) compared to MDA levels in the testes, liver, pancreas, and plasma of diabetic rats without SHE administration (positive control/ C +). The highest dose of SHE treatment (2.1 mL/day) results in decreasing MDA levels were not significantly different (p&gt; 0.05) with the group of non-diabetic rats / negative controls (C-). The conclusion of this study was increasing SHE administration up to 2.1 mL/day result in reducing more of MDA levels in plasma, pancreas, liver, and testes of diabetic rats.

Dihydromyricetin Attenuates Streptozotocin-induced Liver Injury and Inflammation in Rats via Regulation of NF-кB and AMPK Signaling Pathway

Dihydromyricetin (DHM) dramatically improved the quality of life for Streptozotocin (STZ)-induced diabetic rats and significantly increased the activity of antioxidant enzymes in the liver. Moreover, DHM successfully ameliorated diabetes-induced liver damage by suppression of apoptosis in the liver, as indicated by the decreased levels of Bax and cleaved caspase-3. In diabetic rats, the levels of tumor necrosis factor-α and interleukin-1β in the liver were significantly increased. However, the administration of DHM (100–400 mg/kg/day) for 6 weeks restored the cytokine levels to their normal values in a dose-dependent manner in diabetic rats by the regulation of nuclear factor-kappa B signaling pathway. In addition, DHM significantly induced 5′ AMP-activated protein kinase (AMPK) phosphorylation and decreased MyD88, TLR4, p38, GSK-3b protein expression levels in the liver of diabetic rats. In conclusion, DHM could improve STZ-induced liver impairment by preventing oxidative stress, apoptosis, and inflammation.

Zhenqing recipe attenuates non-alcoholic fatty liver disease by regulating the SIK1/CRTC2 signaling in experimental diabetic rats

BackgroundAs a compound Chinese medicine, Zhenqing Recipe (ZQR) has been shown to ameliorate hyperglycemia, hyperlipidemia, fatty liver and insulin resistance in patients with diabetes and diabetic rats. In this paper, we further examined the effect of ZQR on diabetes complicated by non-alcoholic fatty liver disease (NAFLD) and the underlying molecular mechanisms.MethodsDiabetic rats with NAFLD were developed by a high-fat diet (HFD) with low-dose streptozotocin (STZ) injection for 4 weeks. These rats were randomly separated into the diabetic model (DM), ZQR, metformin (Met), adenovirus expressing-salt-induced kinase 1 (Ad-SIK1) and adenovirus labeled with green fluorescent protein (Ad-GFP) groups. The effects on hepatic expression of gluconeogenic genes, glycolipid metabolism and pathological changes were subsequently detected.ResultsSerum glucose, triglycerides (TG), total cholesterol (TC) and hepatic TG were reduced in the ZQR group. The histopathological and immunohistochemical changes in the liver and pancreas in the ZQR group were significantly alleviated. The decrease of SIK1 expression was observed in the liver of diabetic rats induced by HFD and STZ. SIK1 overexpression in the liver relieved hyperglycemia, hyperlipidemia and fatty liver. Both the mRNA and protein levels of CREB-regulated transcription co-activator 2 (CRTC2), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in the liver were drastically reduced, whereas those of SIK1 were markedly increased in the ZQR group compared to levels in the DM group. Compared with the DM group, Ser577 phosphorylation of SIK1 was obviously reduced in the liver, while T182 phosphorylation of SIK1 and S171 phosphorylation of CRTC2 were evidently increased in the Ad-SIK1, Met and ZQR groups.ConclusionsZQR ameliorates hepatic gluconeogenesis and lipid storage in diabetic rats induced by HFD and STZ by activating the SIK1/CRTC2 signaling pathway. Upregulating hepatic SIK1 by ZQR may represent an efficient strategy for treating diabetes with NAFLD.

ε-Viniferin, a promising natural oligostilbene, ameliorates hyperglycemia and hyperlipidemia by activating AMPK in vivo.

ε-Viniferin (VNF), a naturally occurring oligostilbene (a resveratrol dimer), is mainly found in grapes and red wines. However, unlike resveratrol, the biological activity of VNF has not been widely studied. This study was conducted to investigate the beneficial effects of VNF on hyperglycemia and hyperlipidemia and further to reveal the underlying mechanism. The ameliorative effects of VNF in high-fat-diet and streptozotocin-induced type 2 diabetic rats were assessed physiologically, biochemically and histologically after oral administration of VNF (30 mg kg-1 and 60 mg kg-1) for 8 weeks. Western blotting and immunohistochemistry experiments were performed to determine the effects of VNF on the AMPK phosphorylation levels in the livers of diabetic rats. Molecular docking and molecular dynamics simulation were further performed to study the molecular-level interaction between VNF and AMPK. Meanwhile, the protective effects of VNF on the liver and kidney were also evaluated. The results showed that the VNF treatment caused a significant decrease in the concentrations of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low density lipoprotein-cholesterol (LDL-C), and improved the glucose tolerance of diabetic rats. In addition, the liver and kidney damage indices such as alanine aminotransferase (ALT), aspartate aminotransaminase (AST), creatinine (CR), and blood urea nitrogen (BUN) were also lowered and improved. Moreover, VNF could increase the AMPK activation and attenuate histopathological changes in the liver of diabetic rats. The molecular docking and molecular dynamics simulation results revealed for the first time that VNF bound to the hinge region between the α- and β-units of AMPK and interacted with the active site of AMPK. In conclusion, VNF can effectively improve hyperglycemia and hyperlipidemia and exhibit protective effects on the liver and kidney functions. The underlying mechanism of VNF in hyperglycemia and hyperlipidemia may be related to the activation of AMPK in vivo. Our findings indicate that VNF is a potentially useful natural agent for the treatment of metabolic diseases, especially type 2 diabetes and hyperlipidemia.

Fullerene C60Nanoparticles Decrease Liver Oxidative Stress through Increment of Liver Antioxidant Capacity in Streptozotocin-Induced Diabetes in Rats

Chronic hyperglycemia causes oxidative stress in the liver and enhances the hepatic vulnerability to oxidative damage in diabetes mellitus. Since an excellent antioxidative stress property of fullerene C60 nanoparticles has been demonstrated in a wide range of in vitro and in vivo studies, we examined the effect of fullerene C60 nanoparticles on the oxidative stress markers in the liver of streptozotocin-induced diabetes in rats. Male Wistar rats were randomly divided into 4 groups (n = 8 for each group): normal, treated normal, diabetic, and treated diabetic groups. The rats were made diabetic by a single intravenous injection of streptozotocin (50 mg/kg). Treated (normal and diabetic) rats received orally fullerene C60 nanoparticles (1 mg/kg/day) by a gavage tube for 8 weeks. At termination of the study, the oxidative stress parameters were determined in liver tissues, including malondialdehyde (MDA) levels and the activities of catalase (CAT) and superoxide dismutase (SOD) as well as the content of the reduced form of glutathione (GSH). Treatment with fullerene C60 did not change blood glucose of normal and diabetic rats. Diabetes increased MDA levels and CAT activity but decreased GSH content in the liver. Fullerene C60 administration significantly decreased MDA levels and increased the activities of CAT and SOD as well as ameliorated the histopathological changes in the liver of diabetic rats. Taken together, the results of the present study indicated that fullerene C60 nanoparticles could decrease oxidative stress injury in the liver of diabetic rats likely through potentiation of the hepatic antioxidant capacity.