The potential therapeutic effects of Trifolium alexandrinum extract, hesperetin and quercetin against diabetic nephropathy via attenuation of oxidative stress, inflammation, GSK-3β and apoptosis in male rats

AbstractObjective:Oxidative stress has been suggested to increase after electroconvulsive therapy (ECT), a treatment which continues to be the most effective for severe depression. Oxidative stress could potentially be mechanistically involved in both the therapeutic effects and side effects of ECT.Methods:We measured sensitive markers of systemic and central nervous system (CNS) oxidative stress on DNA and RNA (urinary 8-oxodG/8-oxoGuo, cerebrospinal fluid 8-oxoGuo, and brain oxoguanine glycosylase mRNA expression) in male rats subjected to electroconvulsive stimulations (ECS), an animal model of ECT. Due to the previous observations that link hypothalamic–pituitary–adrenal (HPA)-axis activity and age to DNA/RNA damage from oxidation, groups of young and middle-aged male animals were included, and markers of HPA-axis activity were measured.Results:ECS induced weight loss, increased corticosterone (only in middle-aged animals), and decreased cerebral glucocorticoid receptor mRNA expression, while largely leaving the markers of systemic and CNS DNA/RNA damage from oxidation unaltered.Conclusion:These results suggest that ECS is not associated with any lasting effects on oxidative stress on nucleic acids neither in young nor middle-aged rats.

Download Full-text

Cadmium acts as a silent killer of liver by inducing oxidative stress and hepatocellular injury and a possible amelioration by vitamin B12 and folic acid in rat model

Progress in Health Sciences ◽

10.5604/01.3001.0013.3696 ◽

2019 ◽

Vol 1 ◽

pp. 105-117

Author(s):

A. Banerjee ◽

P. Nandi ◽

C. Bhattacharya ◽

Z. Kabir ◽

S. Mukherjee ◽

...

Keyword(s):

Oxidative Stress ◽

Folic Acid ◽

Vitamin B12 ◽

Rat Model ◽

Male Rats ◽

Albino Rats ◽

Therapeutic Effects ◽

Hepatocellular Injury ◽

Male Adult ◽

Wistar Albino Rats

Purpose: To investigate the involvement of oxidative stress in Cadmium (Cd) induced alteration in the functional status of the liver. And to assess the efficacy of folic acid and vitamin B12 in preventing Cd-induced damage in the same. Materials and methods: The experiment was carried out for four weeks. For the experiment, 25 healthy male adult Wistar albino rats were randomly selected and were divided into five equal groups and treated as control, treated with Cd, supplemented with vitamin B12 and folic acid and in the combination of these two. After 28 days the liver function enzymes and oxidative stress parameters were measured. Results: Cd is the silent killer of the hepatic system through the induction of oxidative stress in male rats. From this investigation, it is evident that the folic acid+vitamin B12 possess significant hepatoprotective and antioxidant activity against Cd-induced hepatotoxicity in the rat model. In addition, results revealed that the folic acid alone and or in combination with vitamin B12 blunted the hepatotoxic effect significantly. Conclusions: Based on results obtained, it can be concluded that folic acid and vitamin B12 offer a protective effect in Cd-induced oxidative stress associated with hepatocellular injury. Folic acid and vitamin B12 can be considered as a potent natural antioxidant which has the capacity to provide protection against Cd-induced oxidative stress in the liver in rats. However, to elucidate the exact mechanism of this modulatory effect and to examine its potential therapeutic effects further studies are essential.

Download Full-text

Gold nanoparticles attenuate albuminuria by inhibiting podocyte injury in a rat model of diabetic nephropathy

Drug Delivery and Translational Research ◽

10.1007/s13346-019-00675-6 ◽

2019 ◽

Vol 10 (1) ◽

pp. 216-226 ◽

Cited By ~ 3

Author(s):

Ghada Alomari ◽

Bahaa Al-Trad ◽

Salehhuddin Hamdan ◽

Alaa Aljabali ◽

Mazhar Al-Zoubi ◽

...

Keyword(s):

Oxidative Stress ◽

Gold Nanoparticles ◽

Diabetic Nephropathy ◽

Growth Factor ◽

Protein Expression ◽

Male Rats ◽

Extracellular Matrix Protein ◽

Membrane Thickness ◽

Podocyte Injury ◽

Basement Membrane Thickness

Abstract Several recent studies have reported that gold nanoparticles (AuNPs) attenuate hyperglycemia in diabetic animal models without any observed side effects. The present study was intended to provide insight into the effects of 50-nm AuNPs on diabetic kidney disease. Adult male rats were divided into three groups (n = 7/group): control (non-diabetic, ND), diabetic (D), and diabetic treated intraperitoneally with 50-nm AuNPs (AuNPs + D; 2.5 mg/kg/day) for 7 weeks. Diabetes was induced by a single-dose injection of 55 mg/kg streptozotocin. The result showed that AuNP treatment prevented diabetes-associated increases in the blood glucose level. Reduction in 24-h urinary albumin excretion rate, glomerular basement membrane thickness, foot process width, and renal oxidative stress markers was also demonstrated in the AuNP-treated group. In addition, the results showed downregulation effect of AuNPs in renal mRNA or protein expression of transforming growth factor β1 (TGF-β1), fibronectin, collagen IV, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor-A (VEGF-A). Moreover, the protein expression of nephrin and podocin, podocyte markers, in glomeruli was increased in the AuNPs + D group compared with the D group. These results provide evidence that 50-nm AuNPs can ameliorate renal damage in experimental models of diabetic nephropathy through improving the renal function and downregulating extracellular matrix protein accumulation, along with inhibiting renal oxidative stress and amelioration of podocyte injury.

Download Full-text

Does curcumin or metformin attenuate oxidative stress and diabetic nephropathy in rats?

Journal of Nephropathology ◽

10.15171/jnp.2019.08 ◽

2018 ◽

Vol 8 (1) ◽

pp. 8-8 ◽

Cited By ~ 3

Author(s):

Soheila Asadi ◽

Mohammad Taghi Goodarzi ◽

Jamshid Karimi ◽

Mohammad Hashemnia ◽

Iraj Khodadadi

Keyword(s):

Oxidative Stress ◽

Body Weight ◽

Diabetic Nephropathy ◽

Oxidative Status ◽

P Value ◽

Chow Diet ◽

Therapeutic Effects ◽

Urinary Creatinine ◽

Antioxidant Agents

Background: Since the importance of oxidative stress in the development of diabetic nephropathy (DN) has previously been established, the therapeutic effects of various natural antioxidant agents or synthetic drugs have so far been investigated. Objectives: The aim of this study was to investigate the beneficial effects of curcumin (a natural polyphenol) and metformin (a common therapeutic medicine for type 2 diabetes) on oxidative status in kidney of type 1 diabetic rats. Materials and Methods: In this experimental study 60 male Wistar rats were divided into 10 groups. Type 1 diabetes was induced by streptozotocin. Rats received chow diet and treated with either normal saline in control (N) and diabetic control (D) groups or different doses of metformin (Met) (300 or 500 mg/kg body weight) or curcumin (Cur) (50 or 150 mg/kg body weight) in N+Met300, N+Met500, N+Cur50, N+Cur150, D+Met300, D+Met500, D+Cur50, and D+Cur150 groups. Urinary creatinine, urea, and protein were measured. Total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), and the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase were assessed in kidney tissues. Results: Both metformin and curcumin showed significant effects on urinary creatinine, urea, and protein levels (P value for all was <0.001). Unlike metformin, curcumin completely restored TAC and TOS (P<0.001), and MDA (P=0.012) in kidney tissues and significantly recovered the activities of SOD (P= 0.003), GPx (P< 0.001), and catalase (P=0.011). Conclusions: Curcumin was found more effective than metformin in attenuating oxidative status in DN.

Download Full-text

Role of SIRT1 in Hepatic Encephalopathy: In Vivo and In Vitro Studies Focusing on the NLRP3 Inflammasome

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5522708 ◽

2021 ◽

Vol 2021 ◽

pp. 1-23

Author(s):

Fangzhou Jiao ◽

Yao Wang ◽

Qian Chen ◽

Pan Cao ◽

Chunxia Shi ◽

...

Keyword(s):

Oxidative Stress ◽

Hepatic Encephalopathy ◽

Nlrp3 Inflammasome ◽

Microglial Activation ◽

Male Rats ◽

Therapeutic Effects ◽

Ht22 Cells ◽

Brain Oxidative Stress

Hepatic encephalopathy (HE) is a neuropsychiatric disorder resulting from acute or chronic liver failure. This study is aimed at investigating the therapeutic effects and mechanisms of SIRT1 in thioacetamide- (TAA-) induced rat HE models. A selective activator (CAY10602) and inhibitor (EX527) of SIRT1 were used in this study. All male rats were separated into control, TAA, CAY10602+TAA, and EX527+TAA groups. Histological damage, liver function, serum ammonia, behavioral changes, and brain oxidative stress were measured in each group. Western blotting was used to measure SIRT1, NLRP3, ASC, and IL-1β protein expression. The results showed that CAY10602 alleviated liver injury, improved neurological decline, reduced microglial activation and brain oxidative stress, and improved the survival rates of HE rats. Moreover, CAY10602 inhibited activation of the NLRP3 inflammasome in microglia of the brain cortex in HE rats. Next, cell experiments confirmed that CAY10602 inhibited activation of the NLRP3 inflammasome in BV2 microglial cells. However, inhibition of SIRT1 by EX527 or lentivirus could enhance activation of the NLRP3 inflammasome in this process. Finally, CAY10602 reduced the neurotoxicity induced by high levels of ammonia in HT22 cells. Taken together, CAY10602 alleviates TAA-induced HE by suppressing microglial activation and the NLRP3 inflammasome and reducing the neurotoxicity of NH4Cl in HT22 cells. A pharmacologic activator of SIRT1 may be a promising approach for the treatment of HE.

Download Full-text

High Glucose Increases Metallothionein Expression in Renal Proximal Tubular Epithelial Cells

Experimental Diabetes Research ◽

10.1155/2011/534872 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 18

Author(s):

Daisuke Ogawa ◽

Masato Asanuma ◽

Ikuko Miyazaki ◽

Hiromi Tachibana ◽

Jun Wada ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Vitamin E ◽

Epithelial Cells ◽

High Glucose ◽

Male Rats ◽

Tubular Epithelial Cells ◽

Proximal Tubular Epithelial Cells ◽

Proximal Tubular ◽

Renal Proximal Tubular

Metallothionein (MT) is an intracellular metal-binding, cysteine-rich protein, and is a potent antioxidant that protects cells and tissues from oxidative stress. Although the major isoforms MT-1 and -2 (MT-1/-2) are highly inducible in many tissues, the distribution and role of MT-1/-2 in diabetic nephropathy are poorly understood. In this study, diabetes was induced in adult male rats by streptozotocin, and renal tissues were stained with antibodies for MT-1/-2. MT-1/-2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular epithelial cell line, stimulated with high glucose medium and pretreated with the antioxidant vitamin E. MT-1/-2 expression was gradually and dramatically increased, mainly in the proximal tubular epithelial cells and to a lesser extent in the podocytes in diabetic rats, but was hardly observed in control rats. MT-1/-2 expression was also increased by high glucose stimulation in mProx24 cells. Because the induction of MT was suppressed by pretreatment with vitamin E, the expression of MT-1/-2 is induced, at least in part, by high glucose-induced oxidative stress. These observations suggest that MT-1/-2 is induced in renal proximal tubular epithelial cells as an antioxidant to protect the kidney from oxidative stress, and may offer a novel therapeutic target against diabetic nephropathy.

Download Full-text

Effects of quercetin on methotrexate-induced nephrotoxicity in rats

Human & Experimental Toxicology ◽

10.1177/0960327116637414 ◽

2016 ◽

Vol 36 (1) ◽

pp. 51-61 ◽

Cited By ~ 16

Author(s):

Yasemin Yuksel ◽

Ramazan Yuksel ◽

Murat Yagmurca ◽

Hacer Haltas ◽

Husamettin Erdamar ◽

...

Keyword(s):

Oxidative Stress ◽

Structural Changes ◽

Caspase 3 ◽

Periodic Acid ◽

Antioxidant Properties ◽

Kidney Tissue ◽

Male Rats ◽

Terminal Deoxynucleotidyl Transferase ◽

Control Group ◽

Therapeutic Effects

Objective: This experimental study was conducted to elucidate the possible protective/therapeutic effects of quercetin against methotrexate (Mtx)-induced kidney toxicity with biochemical and histopathological studies. Methods: Twenty-four adult male rats were randomly divided into four groups, as follows: control group (saline intraperitoneally (i.p.), 9 days), Mtx group (20 mg/kg i.p., single dose), Mtx + quercetin group (50 mg/kg quercetin was orally administered 2 days before and 6 days after Mtx administration) and only quercetin group (50 mg/kg oral, 9 days). Structural changes were evaluated by hematoxylin–eosin and periodic acid–Schiff stainings. Apoptotic changes were investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and caspase-3 antibody. Superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured in tissue and plasma samples. Results: Mtx compared with the control group, there was significant increase in nephrotoxic tissue damage findings, in addition to apoptotic index (APOI) and caspase-3 expression ( p < 0.05). Mtx + quercetin group revealed significantly lower histopathological damage and APOI and caspase-3 expression decreased when compared to Mtx group. MDA levels were increased in Mtx group compared to others, and by the use of quercetin, this increase was significantly reduced. SOD levels were higher in Mtx group than others. This increase was evaluated as a relative increase arising from oxidative damage caused by Mtx. Conclusion: As a result, Mtx administration may involve oxidative stress by causing structural and functional damage in kidney tissue in rats. Quercetin reduced the Mtx-induced oxidative stress through its antioxidant properties and so quercetin may be promising to alleviate Mtx-induced renal toxicity.

Download Full-text

Inhibition of TRIM32 Attenuates the Apoptosis, Oxidative Stress and Inflammatory Injury of Podocytes Induced by High Glucose by Affecting the Akt/GSK-3β/Nrf2 Pathway

10.21203/rs.3.rs-551617/v1 ◽

2021 ◽

Author(s):

Zhao Chen ◽

Lifang Tian ◽

Li Wang ◽

Xiaotao Ma ◽

Fuqian Lei ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Inflammatory Response ◽

High Glucose ◽

Glycogen Synthase ◽

Related Factor ◽

Protective Effects ◽

Gsk 3Β ◽

Induced Apoptosis

Abstract Hyperglycemia-induced oxidative stress of podocytes exerts a major role in the pathological process of diabetic nephropathy. Tripartite motif-containing protein 32 (TRIM32) has been reported as a key protein in the modulation of cellular apoptosis and oxidative stress under various pathological processes. However, whether TRIM32 participates in the regulation of high glucose (HG)-induced injury in podocytes has not been investigated. The aims of this work were to assess the possible role of TRIM32 in mediating HG-induced apoptosis, oxidative stress and inflammatory response in podocytes in vitro. Herein, our results showed a marked increase in TRIM32 expression in HG-exposed podocytes. Loss-of-function experiments showed that the knockdown of TRIM32 improved the viability of HG-stimulated podocytes, and suppressed HG-induced apoptosis, oxidative stress and inflammatory response in podocytes. Further investigation revealed that the inhibition of TRIM32 enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling associated with modulation of the Akt/glycogen synthase kinase-3β (GSK-3β) axis in podocytes following HG exposure. However, the suppression of Akt abrogated the TRIM32-knockdown-mediated activation of Nrf2 in HG-exposed podocytes. In addition, the knockdown of Nrf2 markedly abolished the TRIM32-inhibition-induced protective effects in HG-exposed podocytes. In summary, the results of this work show that the inhibition of TRIM32 protects podocytes from HG-induced injury by potentiating Nrf2 signaling via the modulation of Akt/GSK-3β signaling. This study indicates a potential role of TRIM32 in mediating podocyte injury during the progression of diabetic nephropathy.

Download Full-text

Role of Nuclear Factor Erythroid 2-Related Factor 2 in Diabetic Nephropathy

Journal of Diabetes Research ◽

10.1155/2017/3797802 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 18

Author(s):

Wenpeng Cui ◽

Xu Min ◽

Xiaohong Xu ◽

Bing Du ◽

Ping Luo

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Cellular Response ◽

Therapeutic Effects ◽

Related Factor ◽

Nuclear Factor ◽

Urinary Protein Level ◽

Nrf2 Activation ◽

Stage Renal Disease ◽

End Stage

Diabetic nephropathy (DN) is manifested as increased urinary protein level, decreased glomerular filtration rate, and final renal dysfunction. DN is the leading cause of end-stage renal disease worldwide and causes a huge societal healthcare burden. Since satisfied treatments are still limited, exploring new strategies for the treatment of this disease is urgently needed. Oxidative stress takes part in the initiation and development of DN. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in the cellular response to oxidative stress. Thus, activation of Nrf2 seems to be a new choice for the treatment of DN. In current review, we discussed and summarized the therapeutic effects of Nrf2 activation on DN from both basic and clinical studies.

Download Full-text

Targeting Glycogen Synthase Kinase-3βfor Therapeutic Benefit against Oxidative Stress in Alzheimer's Disease: Involvement of the Nrf2-ARE Pathway

International Journal of Alzheimer s Disease ◽

10.4061/2011/985085 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 11

Author(s):

Katja Kanninen ◽

Anthony R. White ◽

Jari Koistinaho ◽

Tarja Malm

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Glycogen Synthase ◽

Glycogen Synthase Kinase ◽

Therapeutic Effects ◽

Related Factor ◽

Nrf2 Pathway ◽

Gsk 3Β

Specific regions of the Alzheimer's disease (AD) brain are burdened with extracellular protein deposits, the accumulation of which is concomitant with a complex cascade of overlapping events. Many of these pathological processes produce oxidative stress. Under normal conditions, oxidative stress leads to the activation of defensive gene expression that promotes cell survival. At the forefront of defence is the nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that regulates a broad spectrum of protective genes. Glycogen synthase kinase-3β (GSK-3β) regulates Nrf2, thus making this kinase a potential target for therapeutic intervention aiming to boost the protective activation of Nrf2. This paper aims to review the neuroprotective role of Nrf2 in AD, with special emphasis on the role of GSK-3β in the regulation of the Nrf2 pathway. We also examine the potential of inducing GSK-3β by small-molecule activators, dithiocarbamates, which potentially exert their beneficial therapeutic effects via the activation of the Nrf2 pathway.

Download Full-text