scholarly journals Astragaloside II Ameliorated Podocyte Injury and Mitochondrial Dysfunction in Streptozotocin-Induced Diabetic Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun Su ◽  
Chongting Gao ◽  
Ling Xie ◽  
Ying Fan ◽  
Yilan Shen ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Tissue Injury ◽  
Morphological Changes ◽  
Mitochondrial Dynamics ◽  
Diabetic Rats ◽  
Control Group ◽  
Protective Effects ◽  
Podocyte Injury ◽  
Renal Histopathology ◽  
Related Proteins

Astragaloside II (AS II), a novel saponin purified from Astragalus membranes, has been reported to modulate the immune response, repair tissue injury, and prevent inflammatory response. However, the protective effects of AS II on podocyte injury in diabetic nephropathy (DN) have not been investigated yet. In this study, we aimed to investigate the beneficial effects of AS II on podocyte injury and mitochondrial dysfunction in DN. Diabetes was induced with streptozotocin (STZ) by intraperitoneal injection at 55 mg/kg in rats. Diabetic rats were randomly divided into four groups, namely, diabetic rats and diabetic rats treated with losartan (10 mg·kg−1·d−1) or AS II (3.2 and 6.4 mg·kg−1·d−1) for 9 weeks. Normal Sprague-Dawley rats were chosen as nondiabetic control group. Urinary albumin/creatinine ratio (ACR), biochemical parameters, renal histopathology and podocyte apoptosis, and morphological changes were evaluated. Expressions of mitochondrial dynamics-related and autophagy-related proteins, such as Mfn2, Fis1, P62, and LC3, as well as Nrf2, Keap1, PINK1, and Parkin, were examined by immunohistochemistry, western blot, and real-time PCR, respectively. Our results indicated that AS II ameliorated albuminuria, renal histopathology, and podocyte foot process effacement and podocyte apoptosis in diabetic rats. AS II also partially restored the renal expression of mitochondrial dynamics-related and autophagy-related proteins, including Mfn2, Fis1, P62, and LC3. AS II also increased the expression of PINK1 and Parkin associated with mitophagy in diabetic rats. Moreover, AS II facilitated antioxidative stress ability via increasing Nrf2 expression and decreasing Keap1 protein level. These results suggested that AS II ameliorated podocyte injury and mitochondrial dysfunction in diabetic rats partly through regulation of Nrf2 and PINK1 pathway. These important findings might provide an innovative therapeutic strategy for the treatment of DN.

scholarly journals Astragalus membranaceus and Panax notoginseng, the Novel Renoprotective Compound, Synergistically Protect against Podocyte Injury in Streptozotocin-Induced Diabetic Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Ruonan Zhai ◽  
Guihua Jian ◽  
Teng Chen ◽  
Ling Xie ◽  
Rui Xue ◽  
...  
Keyword(s):  
Panax Notoginseng ◽  
Diabetic Rats ◽  
Astragalus Membranaceus ◽  
Protective Effects ◽  
The Novel ◽  
Podocyte Injury ◽  
Renal Histopathology ◽  
Foot Process ◽  
Immunofluorescence Labeling ◽  
Renal Expression

This study was aimed at investigating the synergistical protective effects of Astragalus membranaceus (AG) and Panax notoginseng (NG) on podocyte injury in diabetic rats. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin at 55 mg/kg. Diabetic rats were then orally administrated with losartan, AG, NG, and AG plus NG (2 : 1) for 12 weeks. Albuminuria, biochemical markers, renal histopathology, and podocyte number per glomerulus were measured. Podocyte apoptosis was determined by triple immunofluorescence labeling including TUNEL assay, WT1, and DAPI. Renal expression of nephrin, α-dystroglycan, Bax, Bcl-xl, and Nox4 was evaluated by immunohistochemistry, western blot, and RT-PCR. AG plus NG ameliorated albuminuria, renal histopathology, and podocyte foot process effacement to a greater degree than did AG or NG alone. The number of podocytes per glomerulus, as well as renal expression of nephrin, α-dystroglycan, and Bcl-xl, was decreased, while podocyte apoptosis, as well as renal expression of Bax and Nox4, was increased in diabetic rats. All of these abnormalities were partially restored by AG plus NG to a greater degree than did AG or NG alone. In conclusion, AG and NG synergistically ameliorated diabetic podocyte injury partly through upregulation of nephrin, α-dystroglycan, and Bcl-xl, as well as downregulation of Bax and Nox4. These findings might provide a novel treatment combination for DN.

scholarly journals The Protective Effects of Acer okamotoanum and Isoquercitrin on Obesity and Amyloidosis in a Mouse Model

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1353
Author(s):  
Ji Hyun Kim ◽  
Sanghyun Lee ◽  
Eun Ju Cho
Keyword(s):  
Body Weight ◽  
Mouse Model ◽  
High Fat Diet ◽  
Ethyl Acetate Fraction ◽  
Control Group ◽  
Protective Effects ◽  
High Fat ◽  
Acer Okamotoanum ◽  
Related Proteins ◽  
The Brain

Obesity increases risk of Alzheimer’s Disease (AD). A high fat diet (HFD) can lead to amyloidosis and amyloid beta (Aβ) accumulation, which are hallmarks of AD. In this study, protective effects of the ethyl acetate fraction of Acer okamotoanum (EAO) and isoquercitrin were evaluated on obesity and amyloidosis in the HFD- and Aβ-induced mouse model. To induce obesity and AD by HFD and Aβ, mice were provided with HFD for 10 weeks and were intracerebroventricularly injected with Aβ25–35. For four weeks, 100 and 10 mg/kg/day of EAO and isoquercitrin, respectively, were administered orally. Administration of EAO and isoquercitrin significantly decreased body weight in HFD and Aβ-injected mice. Additionally, EAO- and isoquercitrin-administered groups attenuated abnormal adipokines release via a decrease in leptin and an increase in adiponectin levels compared with the control group. Furthermore, HFD and Aβ-injected mice had damaged liver tissues, but EAO- and isoquercitrin-administered groups attenuated liver damage. Moreover, administration of EAO and isoquercitrin groups down-regulated amyloidosis-related proteins in the brain such as β-secretase, presenilin (PS)-1 and PS-2 compared with HFD and Aβ-injected mice. This study indicated that EAO and isoquercitrin attenuated HFD and Aβ-induced obesity and amyloidosis, suggesting that they could be effective in preventing and treating both obesity and AD.

scholarly journals Protective Effects of Green Tea Extract against Hepatic Tissue Injury in Streptozotocin-Induced Diabetic Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Ali Akbar Abolfathi ◽  
Daryoush Mohajeri ◽  
Ali Rezaie ◽  
Mehrdad Nazeri
Keyword(s):  
Green Tea ◽  
Tissue Injury ◽  
Diabetic Rats ◽  
Green Tea Extract ◽  
Hepatic Tissue ◽  
Control Group ◽  
Group 4 ◽  
Group 3 ◽  
Tea Extract ◽  
Group 1

Although diabetic hepatopathy is potentially less common, it may be appropriate for addition to the list of target organ conditions related to diabetes. This study was designed to evaluate the hepatoprotective properties of green tea extract (GTE) in STZ-induced diabetes in rats. Wistar rats were made diabetic through single injection of STZ (75 mg/kg i.p.). The rats were randomly divided into four groups of 10 animals each: Group 1, healthy control; Group 2, nondiabetics treated with GTE administered orally (1.5%, w/v); Group 3, diabetics; Group 4, diabetics treated with GTE (1.5%, w/v) for 8 weeks. Serum biomarkers were assessed to determine hepatic injury. Malondialdehyde (MDA) and reduced glutathione (GSH) contents were measured to assess free radical activity in the liver tissue. Hepatic antioxidant activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) were also determined. The biochemical findings were matched with histopathological verifications. Liver MDA content and serum levels of ALT, AST, ALP, and bilirubin in Group 3 significantly increased compared to Group 1 (P<0.05) and significantly decreased in Group 4 compared to Group 3 (P<0.05). Serum albumin level and GSH, SOD, CAT, and GSH-Px contents of the liver in Group 3 were significantly decreased compared to Group 1 (P<0.05) and were significantly increased in Group 4 compared to Group 3 (P<0.05). Histopathologically, the changes were in the same direction with biochemical findings. This study proved the hepatoprotective activity of GTE in experimentally induced diabetic rats.

scholarly journals The Pathological Features of Common Hereditary Mitochondrial Dynamics Neuropathy

2021 ◽  
Vol 15 ◽  
Author(s):  
Rui Wu ◽  
He Lv ◽  
Hui Wang ◽  
Zhaoxia Wang ◽  
Yun Yuan
Keyword(s):  
Morphological Changes ◽  
Mitochondrial Dynamics ◽  
Deep Tendon Reflex ◽  
Nerve Fibers ◽  
Sensory Loss ◽  
Mitofusin 2 ◽  
Charcot Marie Tooth Disease ◽  
Tendon Reflex ◽  
Unmyelinated Nerve ◽  
Related Proteins

ObjectivesMitofusin 2 and ganglioside-induced differentiation-associated protein 1 are two main mitochondrial dynamics-related proteins. Dysfunction of these two proteins leads to different subtypes of Charcot–Marie–Tooth disease type 2A (CMT2A) and CMT2K. This study aims to report the pathological difference between CMT2A and CMT2K in a large cohort.MethodsThirty patients with molecularly confirmed CMT2A and nine with CMT2K were identified by next-generation sequencing. Sural nerve biopsies were performed in 29 patients.ResultsThe patients with both diseases showed length-dependent neuropathy with distal weakness, sensory loss, and no deep tendon reflex. Optic neuropathy appeared in 3/30 (10%) patients with CMT2A. Tendon contracture appeared in 4/9 (50.0%) patients with CMT2K. Sural biopsy revealed the loss of both myelinated and unmyelinated nerve fibers. Closely packed, irregularly oriented neurofilaments were observed in axons of unmyelinated nerve fibers in both diseases. Another important finding was the ubiquitous presence of smaller, rounded, and fragmented mitochondria in CMT2A and elongated mitochondria in CMT2K in the myelinated and unmyelinated axons.ConclusionThis study confirmed large diversity in phenotypes between CMT2A and CMT2K. Mitochondrial dynamics-related variations can induce different mitochondrial morphological changes and neurofilament accumulation in axons.

scholarly journals Renoprotective Effects of Trigonella foenum and Cinnamon on Type 2 Diabetic Rats

2017 ◽  
Vol 5 (1) ◽  
pp. 17-21
Author(s):  
Seyed Mehrdad Kassaee ◽  
Mohammad Taghi Goodarzi ◽  
Ebrahim Abbasi Oshaghi
Keyword(s):  
Antioxidant Capacity ◽  
Aqueous Extract ◽  
Structural Changes ◽  
Morphological Changes ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Control Group ◽  
Chow Diet ◽  
Plasma Urea ◽  
Cinnamon Extract

Background: Herbal medicine is used in all parts of the world mainly for prevention and treatment of various disorders due to better cultural suitability, lower cost and less side effects. Objectives: The aim of this study was to determine the hypoglycemic and kidney-protective effects of the aqueous extract of Trigonella foenum and Cinnamon on diabetic rats. Methods: In this experimental study, rats were randomly divided into 6 groups as follows: Group 1: control group in which animals received chow diet, group 2: diabetic rats, group 3: diabetic rat + 2% T. foenum extract (w/w), group 4: diabetic rat + 8% of Trigonella foenum extract (w/w), group 5: diabetic rat + 2% Cinnamon extract (w/w) and group 6: diabetic rat + 8% of Cinnamon extract (w/w). Aqueous extract of T. foenum leaves and Cinnamon were administered to diabetic rats for 4 weeks. The malondialdehyde (MDA) level and total antioxidant capacity were also measured in kidney of the animals. In addition, morphological changes of the kidney were also analyzed by the light microscope. Results: Trigonella foenum and Cinnamon extract in diabetic animals significantly reduced MDA levels and restored antioxidant capacity (P<.05). T. foenum and Cinnamon also normalized plasma urea and creatinine concentration in diabetic rats (P<.05). Administration of T. foenum and Cinnamon extract especially at the dose of 8 mg/kg normalized histopatholgical changes of kidney in diabetic animal. Conclusions: The findings of this experiment showed that T. foenum extract and Cinnamon restored antioxidant capacity and structural changes of kidney.

scholarly journals Mfn2 Regulates High Glucose-Induced MAMs Dysfunction and Apoptosis in Podocytes via PERK Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Yun Cao ◽  
Zhaowei Chen ◽  
Jijia Hu ◽  
Jun Feng ◽  
Zijing Zhu ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
High Glucose ◽  
Diabetic Rats ◽  
Mitochondrial Morphology ◽  
Podocyte Injury ◽  
Unfolded Protein ◽  
Mitochondrial Functions ◽  
Protein Response ◽  
Apoptotic Effects

The endoplasmic reticulum (ER) stress and mitochondrial dysfunction in high glucose (HG)-induced podocyte injury have been demonstrated to the progression of diabetic kidney disease (DKD). However, the pathological mechanisms remain equivocal. Mitofusin2 (Mfn2) was initially identified as a dynamin-like protein involved in fusing the outer mitochondrial membrane (OMM). More recently, Mfn2 has been reported to be located at the ER membranes that contact OMM. Mitochondria-associated ER membranes (MAMs) is the intercellular membrane subdomain, which connects the mitochondria and ER through a proteinaceous tether. Here, we observed the suppression of Mfn2 expression in the glomeruli and glomerular podocytes of patients with DKD. Streptozotocin (STZ)-induced diabetic rats exhibited abnormal mitochondrial morphology and MAMs reduction in podocytes, accompanied by decreased expression of Mfn2 and activation of all three unfolded protein response (UPR) pathways (IRE1, ATF6, and PERK). The HG-induced mitochondrial dysfunction, MAMs reduction, and increased apoptosis in vitro were accompanied by the downregulation of Mfn2 and activation of the PERK pathway. Mfn2 physically interacts with PERK, and HG promotes a decrease in Mfn2-PERK interaction. In addition, Mfn2-silenced podocytes showed mitochondrial dysfunction, MAMs reduction, activation of PERK pathway, and increased apoptosis. Conversely, all these effects of HG stimulation were alleviated significantly by Mfn2 overexpression. Furthermore, the inhibition of PERK phosphorylation protected mitochondrial functions but did not affect the expression of Mfn2 in HG-treated podocytes. Therefore, this study confirmed that Mfn2 regulates the morphology and functions of MAMs and mitochondria, and exerts anti-apoptotic effects on podocytes by inhibiting the PERK pathway. Hence, the Mfn2-PERK signaling pathway may be a new therapeutic target for preventing podocyte injury in DKD.

The Beneficial Effects of Trimetazidine on Reperfusion–Induced Arrhythmia in Diabetic Rats

2018 ◽  
Vol 127 (05) ◽  
pp. 320-325 ◽  
Author(s):  
Fatemeh Ramezani-Aliakbari ◽  
Mohammad Badavi ◽  
Mahin Dianat ◽  
Seyed Mard ◽  
Akram Ahangarpour
Keyword(s):  
Infarct Size ◽  
Repeated Measures ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cardiac Contractility ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Control Group ◽  
Protective Effects ◽  
Sprague Dawley

AbstractTrimetazidine (TMZ), as an anti-ischemic drug, plays a critical role in protecting against cardiovascular complications induced by diabetes. This study was therefore aimed to evaluate the protective effects of TMZ on reperfusion-induced arrhythmias in the diabetic rats. Male Sprague-Dawley rats (250±20 g) were randomly assigned to four (n=8): control rats (C), alloxan induced diabetic rats (D), diabetic rats treated with TMZ (10 mg/kg, D+T10), diabetic rats treated with TMZ (30 mg/kg, D+T30). TMZ was treated orally once daily for 8 weeks. Diabetes was induced by a single intraperitoneal injection of alloxan (120 mg/kg). Ischemia-reperfusion (I/R) was carried out via 30 min of ischemia and following120-min reperfusion. The magnitude and score of arrhythmia, the left ventricular function, infarct size, lactate dehydrogenase (LDH), myocardial creatine kinase (CK-MB) and troponin (cTnI) were measured. The findings were evaluated by two-way repeated measures and one-way ANOVA followed by LSD post hoc test and Fisher's exact test for incidence percentage. The duration, incidence and score of arrhythmia (p<0.001), infarct size (p<0.01) were significantly increased, the cardiac contractility (±dp/dt), LDH, CK-MB (p<0.001) and cTnI (p<0.05) were significantly decreased in the diabetic rats in comparison with the control group. However, treatment with TMZ in the diabetic rats was significantly improved the duration (p<0.001), incidence and score of arrhythmia,±dp/dt LDH, CK-MB, cTnI (p<0.05) and infarct size (p<0.01) in comparison with the untreated diabetic group. The present study indicates anti-arrhythmic effect of TMZ in reducing arrhythmias induced by reperfusion in the diabetic rats.

Protective effects of saffron (its active constituent, crocin) on nephropathy in streptozotocin-induced diabetic rats

2014 ◽  
Vol 34 (2) ◽  
pp. 127-134 ◽  
Author(s):  
E Altinoz ◽  
Z Oner ◽  
H Elbe ◽  
Y Cigremis ◽  
Y Turkoz
Keyword(s):  
Plasma Levels ◽  
Heart Defects ◽  
Ischemia Reperfusion ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Diabetic Rats ◽  
Control Group ◽  
Protective Effects ◽  
Active Constituent ◽  
Hydropic Degeneration

The reactive oxygen species take role in pathogenesis of many diseases including hypoxia, hypercholesterolemia, atherosclerosis, nephropathy, hypertension, ischemia–reperfusion damage, and heart defects. The aim of this study was to evaluate whether crocin administration could protect kidney injury from oxidative stress in streptozotocin-induced diabetic rats. The rats were randomly divided into 3 groups each containing 10 animals as follows: group 1, control group; group 2, diabetes mellitus (DM) group; and group 3, DM + crocin group. At the end of the study, trunk blood was collected to determine the plasma levels of blood urea nitrogen (BUN) and creatinine (Cr). The kidney tissue was removed, and biochemical and histological changes were examined. Diabetes caused a significant increase in malondialdehyde (MDA) and xanthine oxidase (XO) activities and a decrease in glutathione (GSH) contents (  p < 0.01) when compared with control group in the rat kidneys. Crocin given to DM rats significantly decreased MDA (  p < 0.01) and XO (  p < 0.05) activities and elevated GSH (  p < 0.05) contents when compared with DM group. Plasma levels of BUN and Cr were significantly higher in the DM group when compared with the control group (  p < 0.01). Pretreatment of the DM animals with crocin decreased the high level of serum Cr and BUN. Control group was normal in histological appearance, but congestion, severe inflammation, tubular desquamation, tubular necrosis, and hydropic degeneration in tubular cells were observed in the DM group. Histopathological changes markedly reduced, and appearance of kidney was nearly similar to control group in DM + crocin group. Our results show that crocin could be beneficial in reducing diabetes-induced renal injury.

scholarly journals Comparison of Oxidant/Antioxidant, Detoxification Systems in Various Tissue Homogenates and Mitochondria of Rats with Diabetes Induced by Streptozocin

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Veysel Kenan Çelık ◽  
Zeynep Deniz Şahın ◽  
İsmail Sari ◽  
Sevtap Bakir
Keyword(s):  
Oxidative Stress ◽  
Tissue Injury ◽  
Total Antioxidant Status ◽  
Diabetic Rats ◽  
Stress Index ◽  
Control Group ◽  
Cardiac Tissues ◽  
Mitochondrial Fractions ◽  
Total Antioxidant ◽  
Tissue Homogenates

Objective. Oxidative stress is considered to be the main factor in the development of diabetic complications and tissue injury. our objective was to investigate and compare the oxidant/antioxidant conditions and detoxification mechanisms of the liver, lung, kidney, cardiac tissues, and mitochondria of rats with diabetes induced by streptozocin (STZ).Methods. Rats with diabetes induced by streptozocin were anesthetized by administering 90 mg/kg ketamine hydrochloride and 3 mg/kg xylazine hydrochloride. Thoracic cavities were incised open; liver, lung, kidney, and cardiac tissues were removed and stored at−70°C. All samples were homogenized and mitochondrial fractions were separated. Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Oxidative Stress Index (OSI), Paraoxonase (PON), Arylesterase, Catalase (Cat), Malondialdehyde (MDA), and Glutathion-S-transferase were measured in each fraction.Results. MDA and TOS levels were significantly increased in liver tissues, and T OS and OSI were increased in the mitochondrial fractions of diabetic rats. These increases were not statistically significant compared to the control group. No significant differences were determined in the antioxidant and GST activities.Conclusion. According to our results, oxidative stress has not developed in rats with diabetes induced by streptozocin. The detoxification system was induced; however, this induction did not differ significantly from the controls.

scholarly journals The Protective Effects of Insulin and Natural Honey against Hippocampal Cell Death in Streptozotocin-Induced Diabetic Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Iraj Jafari Anarkooli ◽  
Hossein Barzegar Ganji ◽  
Maryam Pourheidar
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Living Cells ◽  
Diabetic Rats ◽  
Control Group ◽  
Protective Effects ◽  
Hippocampal Cell ◽  
Group I ◽  
Group D

We investigated the effects of insulin and honey as antioxidants to prevent the hippocampal cell death in streptozotocin-induced diabetic rats. We selected sixty Wister rats (5 groups of 12 animals each), including the control group (C), and four diabetic groups (control (D) and 3 groups treated with insulin (I), honey (H), and insulin plus honey (I + H)). Diabetes was induced by streptozotocin injection (IP, 60 mg/kg). Six weeks after the induction of diabetes, the group I received insulin (3-4 U/kg/day, SC), group H received honey (5 mg/kg/day, IP), and group I + H received a combination of the above at the same dose. Groups C and D received normal saline. Two weeks after treatment, rats were sacrificed and the hippocampus was extracted. Neuronal cell death in the hippocampal region was examined using trypan blue assay, “H & E” staining, and TUNEL assay. Cell viability assessment showed significantly lower number of living cells in group D than in group C. Besides, the mean number of living cells was significantly higher in group I, H, and I + H compared to group D. Therefore, it can be concluded that the treatment of the diabetic rats with insulin, honey, and a combination of insulin and honey can prevent neuronal cell death in different hippocampal areas of the studied samples.

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