scholarly journals Bitter Gourd Honey Ameliorates Hepatic and Renal Diabetic Complications on Type 2 Diabetes Rat Models by Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms

Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2872
Author(s):  
Chandra Sekhar Arigela ◽  
Giribabu Nelli ◽  
Siew Hua Gan ◽  
Kuttulebbai Nainamohamed Salam Sirajudeen ◽  
Kumarathevan Krishnan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Complications ◽  
Diabetic Rats ◽  
Male Rats ◽  
Bitter Gourd ◽  
Liver And Kidney ◽  
Streptozotocin Induced Diabetes ◽  
Treatment Of Diabetes ◽  
Anti Inflammatory ◽  
Apoptotic Effects

Honey has several pharmacological effects, including anti-diabetic activity. However, the effectiveness of bitter gourd honey (BGH) in the treatment of diabetes mellitus (DM) is unknown. The aim of this study was to determine the antioxidant, anti-inflammatory, and anti-apoptotic properties of BGH on the kidney and liver of a streptozotocin-induced diabetes rat model. Methods: A single dose (nicotinamide 110 mg/kg, streptozotocin (STZ) 55 mg/kg, intraperitoneal (i.p.)) was used to induce DM in male rats. For 28 days, normal or diabetic rats were administered 1 g/kg/day and 2 g/kg/day of BGH orally. After the treatment, blood, liver, and kidney samples were collected and analysed for biochemical, histological, and molecular parameters. In addition, liquid chromatography–mass spectrometry (LC-MS) was used to identify the major bioactive components in BGH. Results: The administration of BGH to diabetic rats resulted in significant reductions in alanine transaminase (ALT),aspartate aminotransferase (AST), creatinine, and urea levels. Diabetic rats treated with BGH showed lesser pathophysiological alterations in the liver and kidney as compared to non-treated control rats. BGH-treated diabetic rats exhibited reduced levels of oxidative stress (MDA levels), inflammatory (MYD88, NFKB, p-NFKB, IKKβ), and apoptotic (caspase-3) markers, as well as higher levels of antioxidant enzymes (SOD, CAT, and GPx) in the liver and kidney. BGH contains many bioactive compounds that may have antioxidative stress, anti-inflammatory, and anti-apoptotic effects. Conclusion: BGH protected the liver and kidney in diabetic rats by reducing oxidative stress, inflammation, and apoptosis-induced damage. As a result, BGH can be used as a potential therapy to ameliorate diabetic complications.

The protective role of luteolin against the methotrexate-induced hepato-renal toxicity via its antioxidative, anti-inflammatory, and anti-apoptotic effects in rats

2021 ◽  
pp. 096032712199190
Author(s):  
AA Dar ◽  
A Fehaid ◽  
S Alkhatani ◽  
S Alarifi ◽  
WS Alqahtani ◽  
...  
Keyword(s):  
Renal Toxicity ◽  
Histopathological Examination ◽  
Protective Role ◽  
Male Rats ◽  
Antioxidant Enzyme Activities ◽  
Serum Samples ◽  
Liver And Kidney ◽  
Anti Inflammatory ◽  
Induced Changes ◽  
Apoptotic Effects

Methotrexate (MTX) is frequently used drug in treatment of cancer and autoimmune diseases. Unfortunately, MTX has many side effects including the hepato-renal toxicity. In this study, we hypothesized that Luteolin (Lut) exhibits protective effect against the MTX-induced hepato-renal toxicity. In order to investigate our hypothesis, the experiment was designed to examine the effect of exposure of male rats to MTX (20 mg/kg, i.p., at day 9) alone or together with Lut (50 mg/kg, oral for 14 days) compared to the control rats (received saline). The findings demonstrated that MTX treatment induced significant increases in the liver and kidney functions markers in serum samples including Aspartate transaminase (AST), Alanine transaminase (ALT), creatinine, urea and uric acid. MTX also mediated an oxidative stress expressed by elevated malondialdehyde (MDA) level and decreased level of reduced glutathione (GSH), antioxidant enzyme activities, and downregulation of the Nrf2 gene expression as an antioxidant trigger. Moreover, the inflammatory markers (NF-κB, TNF-α, and IL-1β) were significantly elevated upon MTX treatment. In addition, MTX showed an apoptotic response mediated by elevating the pro-apoptotic (Bax) and lowering the anti-apoptotic (Bcl-2) proteins. All of these changes were confirmed by the observed alterations in the histopathological examination of the hepatic and renal tissues. Lut exposure significantly reversed all the MTX-induced changes in the measured parameters suggesting its potential protective role against the MTX-induced toxicity. Finally, our findings concluded the antioxidative, anti-inflammatory and anti-apoptotic effects of Lut as a mechanism of its protective role against the MTX-induced hepato-renal toxicity in rats.

Inhibitory Effect of Astraxanthin Combined with Flavangenol® on Oxidative Stress Biomarkers in Streptozotocin-Iduced Diabetic Rats

2008 ◽  
Vol 78 (45) ◽  
pp. 175-182 ◽  
Author(s):  
Masako Nakano ◽  
Natsumi Orimo ◽  
Nakako Katagiri ◽  
Masahito Tsubata ◽  
Jiro Takahashi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxide ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Control Group ◽  
Cataract Formation ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
Liver And Kidney ◽  
Streptozotocin Induced Diabetes

In this study, the effect of dietary antioxidants, such as astaxanthin and Flavangenol®, and a combination of both, in counteracting oxidative stress in streptozotocin-induced diabetes was investigated. Streptozotocin-induced diabetic rats were divided into four groups: control, astaxanthin, Flavangenol, and combined astaxanthin and Flavangenol (mix group). Each group other than the control group was fed with an astaxanthin diet (0.1 g/kg), Flavangenol diet (2.0 g/kg), or an astaxanthin (0.1 g/kg)-Flavangenol (2.0 g/kg) mixture diet, respectively. After 12 weeks of feeding, the results showed that the lipid peroxide levels of plasma and lens and the plasma triglyceride (TG) level in the mix group were significantly decreased by 44%, 20%, and 20%, respectively, compared with the control group. In the mix group, lipid peroxidation was also significantly reduced by 70% in the liver and 20% in the kidney compared with the control group. Furthermore, the level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the mix group was significantly lower, 36%, than the control group. The α-tocopherol concentrations in the plasma, liver, and kidney in the astaxanthin and mix groups were significantly higher, 3-9 times, than in the control group. The degree of cataract formation in the Flavangenol and mix groups tended to be lower than the control group. These results indicate that the combination of astaxanthin with Flvangenol has an improved protective effect on oxidative stress associated with streptozotocin-induced diabetes than either agent used alone. Thus, this combination may be beneficial in preventing the progression of diabetic complications.

Eudragit L-100 Capsules Aromatize and Quaternerize Chitosan for Insulin Nanoparticle Oral Delivery During Toxic Oxidative Stress in Rat Liver and Kidney

2020 ◽  
Vol 8 (3) ◽  
pp. 239-254 ◽  
Author(s):  
Reza Mahjub ◽  
Farzane K. Najafabadi ◽  
Narges Dehkhodaei ◽  
Nejat Kheiripour ◽  
Amir N. Ahmadabadi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oral Administration ◽  
Oral Delivery ◽  
Biochemical Parameters ◽  
Kidney Injury ◽  
Regular Insulin ◽  
Treated Group ◽  
Histopathological Change ◽  
Diabetic Rats ◽  
Liver And Kidney

Background: Insulin, like most peptides, is classified as a hydrophilic and macromolecular drug that is considered as a low permeable and unstable compound in the gastrointestinal (GI) tract. The acidic condition of the stomach can degrade insulin molecules. Moreover, the presence of proteolytic activities of some enzymes such as trypsin and chymotrypsin can hydrolyze amide-bonds between various amino-acids in the structures of peptides and proteins. However, due to its simplicity and high patient compliance, oral administration is the most preferred route of systemic drug delivery, and for the development of an oral delivery system, some obstacles in oral administration of peptides and proteins including low permeability and low stability of the proteins in GI should be overcome. Objective: In this study, the effects of orally insulin nanoparticles (INPs) prepared from quaternerized N-aryl derivatives of chitosan on the biochemical factors of the liver in diabetic rats were studied. Methods: INPs composed of methylated (amino benzyl) chitosan were prepared by the PEC method. Lyophilized INPs were filled in pre-clinical capsules, and the capsules were enteric-coated with Eudragit L100. Twenty Male Wistar rats were randomly divided into four groups: group1: normal control rats, group 2: diabetic rats, group 3: diabetic rats received capsules INPs(30 U/kg/day, orally), group 4: the diabetic rats received regular insulin (5 U/kg/day, subcutaneously). At the end of the treatment, serum, liver and kidney tissues were collected. Biochemical parameters in serum were measured using spectrophotometric methods. Also, oxidative stress was measured in plasma, liver and kidney. Histological studies were performed using H and E staining . Results: Biochemical parameters, and liver and kidney injury markers in serum of the diabetic rats that received INPs improved significantly compared with the diabetic group. INPs reduced oxidative toxic stress biomarkers in serum, liver and kidney of the diabetic treated group. Furthermore, a histopathological change was developed in the treated groups. Conclusion: Capsulated INPs can prevent diabetic liver and oxidative kidney damages (similar regular insulin). Therefore oral administration of INPs appears to be safe. Lay Summary: Although oral route is the most preferred route of administration, but oral delivery of peptides and proteins is still a challenging issue. Diabetes Mellitus may lead to severe complications, which most of them are life-threatening. In this study, we are testing the toxicity of oral insulin nanoparticles in kidney and liver of rats. For this investigation, we will prepare insulin nanoparticles composed of a quaternized derivative of chitosan. The nanoparticles will be administered orally to rats and the level of oxidative stress in their liver and kidney will be determined. The data will be compared to the subcutaneous injection of insulin.

Vasopressin V1 and V2 receptors in diabetes mellitus

1994 ◽  
Vol 266 (2) ◽  
pp. E217-E223 ◽  
Author(s):  
D. Trinder ◽  
P. A. Phillips ◽  
J. M. Stephenson ◽  
J. Risvanis ◽  
A. Aminian ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Inositol Phosphate ◽  
Free Water ◽  
Diabetic Rats ◽  
Biological Responses ◽  
Liver And Kidney ◽  
Streptozotocin Induced Diabetes ◽  
V2 Receptor ◽  
Plasma Arginine ◽  
Long Acting

Diabetes mellitus causes hypertonicity, increased plasma arginine vasopressin (AVP), polydipsia, and polyuria. Downregulation of AVP V2 receptors may contribute to the polyuria through diminished V2 receptor-mediated free water retention. After 2 wk of streptozotocin-induced diabetes mellitus, the diabetic rats had raised plasma glucose, AVP, and osmolality levels (P < 0.001) compared with nondiabetic controls (Sham). Insulin treatment (4 U long-acting insulin sc, daily) partially lowered these values (P < 0.01). There was a reduction in the number of renal and hepatic V1 receptors in the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The receptor affinity remained unchanged. In parallel, there was a reduction in maximum AVP-activated total inositol phosphate production in the liver and kidney of the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The density and affinity of renal V2 receptors and AVP-stimulated adenosine 3',5'-cyclic monophosphate production in the diabetic and diabetic+insulin animals were unchanged compared with the sham. These results demonstrate differential regulation of AVP receptors and suggest that downregulation of renal V2 receptors does not contribute to the polyuria of diabetes. In contrast, downregulation of V1 receptors might contribute to diminished V1 receptor-mediated biological responses to AVP seen in diabetes mellitus.

scholarly journals Therapeutic Potentials of Extracellular Vesicles for the Treatment of Diabetes and Diabetic Complications

2020 ◽  
Vol 21 (14) ◽  
pp. 5163 ◽  
Author(s):  
Wei Hu ◽  
Xiang Song ◽  
Haibo Yu ◽  
Jingyu Sun ◽  
Yong Zhao
Keyword(s):  
Extracellular Vesicles ◽  
Diabetic Complications ◽  
Therapeutic Potential ◽  
Cell Communication ◽  
Bioactive Molecules ◽  
Future Research ◽  
Cell Based Therapy ◽  
Liver And Kidney ◽  
Life Threatening ◽  
Treatment Of Diabetes

Extracellular vesicles (EVs), including exosomes and microvesicles, are nano-to-micrometer vesicles released from nearly all cellular types. EVs comprise a mixture of bioactive molecules (e.g., mRNAs, miRNAs, lipids, and proteins) that can be transported to the targeted cells/tissues via the blood or lymph circulation. Recently, EVs have received increased attention, owing to their emerging roles in cell-to-cell communication, or as biomarkers with the therapeutic potential to replace cell-based therapy. Diabetes comprises a group of metabolic disorders characterized by hyperglycemia that cause the development of life-threatening complications. The impacts of conventional clinical treatment are generally limited and are followed by many side effects, including hypoglycemia, obesity, and damage to the liver and kidney. Recently, several studies have shown that EVs released by stem cells and immune cells can regulate gene expression in the recipient cells, thus providing a strategy to treat diabetes and its complications. In this review, we summarize the results from currently available studies, demonstrating the therapeutic potentials of EVs in diabetes and diabetic complications. Additionally, we highlight recommendations for future research.

Hydrogen sulfide modulates IL-6/STAT3 pathway and inhibits oxidative stress, inflammation, and apoptosis in rat model of methotrexate hepatotoxicity

2019 ◽  
Vol 39 (1) ◽  
pp. 77-85 ◽  
Author(s):  
AA Fouad ◽  
HM Hafez ◽  
AAH Hamouda
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Nuclear Factor Κb ◽  
Ruthenium Red ◽  
Transient Receptor Potential Vanilloid ◽  
Stat3 Pathway ◽  
Anti Inflammatory ◽  
Apoptotic Effects

Methotrexate (MTX) is a commonly used anticancer and immunosuppressive agent. However, MTX can induce hepatotoxicity due to oxidative stress, inflammation, and apoptosis. Hydrogen sulfide (H2S), the endogenous gaseous molecule, has antioxidant, anti-inflammatory, and anti-apoptotic effects. The present work explored the probable protective effect of H2S against MTX hepatotoxicity in rats and also the possible mechanisms underlying this effect. MTX was given at a single intraperitoneal (i.p.) dose of 20 mg/kg. Sodium H2S (56 µmol /kg/day, i.p.), as H2S donor, was given for 10 days, starting 6 days before MTX administration. H2S significantly reduced serum alanine aminotransferase, hepatic malondialdehyde, interleukin 6, nuclear factor κB p65, cytosolic cytochrome c, phosphorylated signal transducer and activator of transcription 3, and Bax/Bcl-2 ratio and significantly increased hepatic total antioxidant capacity and endothelial nitric oxide synthase (eNOS) in rats received MTX. In addition, H2S minimized the histopathological injury and significantly decreased the expression of STAT3 in liver tissue of MTX-challenged rats. The effects of H2S were significantly antagonized by administration of glibenclamide as KATP channel blocker, Nω-nitro-l-arginine, as eNOS inhibitor, or ruthenium red, as transient receptor potential vanilloid 1 (TRPV1) antagonist. It was concluded that H2S provided significant hepatoprotection in MTX-challenged rats through its antioxidant, anti-inflammatory, anti-apoptotic effects. These effects are most probably mediated by the ability of H2S to act as IL-6/STAT3 pathway modulator, KATP channel opener, eNOS activator, and TRPV1 agonist.

scholarly journals Electrospun Nanofibers Loaded with Quercetin Promote the Recovery of Focal Entrapment Neuropathy in a Rat Model of Streptozotocin-Induced Diabetes

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Chonlathip Thipkaew ◽  
Jintanaporn Wattanathorn ◽  
Supaporn Muchimapura
Keyword(s):  
Oxidative Stress ◽  
Functional Recovery ◽  
Electrospun Nanofibers ◽  
Diabetic Rats ◽  
Nerve Lesion ◽  
Electrospinning Technique ◽  
Oxidative Stress Status ◽  
Male Wistar Rats ◽  
Streptozotocin Induced Diabetes ◽  
The Right

In this study, quercetin-loaded zein-based nanofibers were developed using electrospinning technique. The therapeutic effect of these quercetin-loaded nanofibers on neuropathy in streptozotocin- (STZ-) induced diabetes in rats was assessed. Diabetic condition was induced in male Wistar rats by STZ, after which a crush injury of the right sciatic nerve was performed to induce mononeuropathy. Functional recovery was assessed using walking track analysis, measurements of foot withdrawal reflex, nerve conduction velocity, and morphological analysis. The oxidative stress status and the ratio of phosphorylated extracellular recognition kinase (pERK)/extracellular recognition kinase (ERK) expression in the nerve lesion were also assessed in order to elucidate the potential mechanisms involved. Results showed that quercetin-loaded zein-based nanofibers slightly enhanced functional recovery from neuropathy in STZ-diabetic rats. The potential mechanism might partially involve improvements in oxidative stress status and the ratio of pERK/ERK expression in the nerve lesion.

Sign in / Sign up

Export Citation Format

Share Document