scholarly journals Cyclosporine-A Attenuates Retinal Inflammation by Inhibiting HMGB-1 Formation in Rats with Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Peng Wang ◽  
Fei Chen ◽  
Xuedong Zhang
Keyword(s):  
Cyclosporine A ◽  
Inflammatory Diseases ◽  
Morphological Changes ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Diabetic Retina ◽  
Tnf Α ◽  
Type 2 Diabetic

Abstract Background:Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy. Methods:Male Sprague-Dawley rats were established to type 2 diabetic model.After 6 weeks, diabetic rats and normal controls were intravitreally injected with Cs-A (42 ng/2 μL) to the left eye, and 2μL DMSO to the right eye for the control. Another part of normal wild-type rats was subjected to intravitreal injections into the left eyes with 5 μL PBS or HMGB-1 (5 ng/5 μL) or HMGB-1(5 ng/5 μL) plus Cs-A (42 ng/2 μL), respectively. Retinal morphological changes were observed with hematoxylin–eosin staining. Expressions of HMGB-1, IL-1β and TNF-α were detected by immunohistochemistry, ELISA or western blot. Results:Retinal expression levels of IL-1β and TNF-α were upregulated in type 2 diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in diabetic retina and relieved the retinopathy in type 2 diabetic rats. Conclusions:Intravitreal administration of Cs-A showed a protective effect on retina of diabetic rats, possibly by downregulating retinal expressions of IL-1β and TNF-α via the suppression of HMGB-1.

scholarly journals Cyclosporine-A Attenuates Retinal Inflammation by Inhibiting HMGB-1 Formation in Rats with Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Peng Wang ◽  
Fei Chen ◽  
Xuedong Zhang
Keyword(s):  
Cyclosporine A ◽  
Inflammatory Diseases ◽  
Morphological Changes ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Diabetic Retina ◽  
Tnf Α ◽  
Type 2 Diabetic

Abstract Background:Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy. Methods:Male Sprague-Dawley rats were established to type 2 diabetic model.After 6 weeks, diabetic rats and normal controls were intravitreally injected with Cs-A (42 ng/2 μL) to the left eye, and 2μL DMSO to the right eye for the control. Another part of normal wild-type rats was subjected to intravitreal injections into the left eyes with 5 μL PBS or HMGB-1 (5 ng/5 μL) or HMGB-1(5 ng/5 μL) plus Cs-A (42 ng/2 μL), respectively. Retinal morphological changes were observed with hematoxylin–eosin staining. Expressions of HMGB-1, IL-1β and TNF-α were detected by immunohistochemistry, ELISA or western blot. Results:Retinal expression levels of IL-1β and TNF-α were upregulated in type 2 diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in diabetic retina and relieved the retinopathy in type 2 diabetic rats. Conclusions:Intravitreal administration of Cs-A showed a protective effect on retina of diabetic rats, possibly by downregulating retinal expressions of IL-1β and TNF-α via the suppression of HMGB-1.

scholarly journals Cyclosporine-A Attenuates Retinal Inflammation by Inhibiting HMGB-1 Formation in Rats with Type 2 Diabetes Mellitus

2019 ◽  
Author(s):  
Peng Wang ◽  
Fei Chen ◽  
Xuedong Zhang
Keyword(s):  
Cyclosporine A ◽  
Inflammatory Diseases ◽  
Morphological Changes ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Diabetic Retina ◽  
Tnf Α ◽  
Type 2 Diabetic

Abstract Background:Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy. Methods:Male Sprague-Dawley rats were established to type 2 diabetic model.After 6 weeks, diabetic rats and normal controls were intravitreally injected with Cs-A (42 ng/2 μL) to the left eye, and 2μL DMSO to the right eye for the control. Another part of normal wild-type rats was subjected to intravitreal injections into the left eyes with 5 μL PBS or HMGB-1 (5 ng/5 μL) or HMGB-1(5 ng/5 μL) plus Cs-A (42 ng/2 μL), respectively. Retinal morphological changes were observed with hematoxylin–eosin staining. Expressions of HMGB-1, IL-1β and TNF-α were detected by immunohistochemistry, ELISA or western blot. Results:Retinal expression levels of IL-1β and TNF-α were upregulated in type 2 diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in diabetic retina and relieved the retinopathy in type 2 diabetic rats. Conclusions:Intravitreal administration of Cs-A showed a protective effect on retina of diabetic rats, possibly by downregulating retinal expressions of IL-1β and TNF-α via the suppression of HMGB-1.

scholarly journals Effect of Aspirin on the Expression of Hepatocyte NF-κB and Serum TNF-α in Streptozotocin-Induced Type 2 Diabetic Rats

2011 ◽  
Vol 26 (6) ◽  
pp. 765 ◽  
Author(s):  
Xiaodong Sun ◽  
Fang Han ◽  
Junling Yi ◽  
Lina Han ◽  
Ben Wang
Keyword(s):  
Diabetic Rats ◽  
Tnf Α ◽  
Type 2 Diabetic

scholarly journals Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated type 2 diabetic rats

2013 ◽  
Vol 218 (3) ◽  
pp. 255-262 ◽  
Author(s):  
C Y Shan ◽  
J H Yang ◽  
Y Kong ◽  
X Y Wang ◽  
M Y Zheng ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Intestinal Barrier ◽  
Resistance Index ◽  
Diabetic Rats ◽  
Diabetic Patients ◽  
Sprague Dawley ◽  
Type 2 Diabetic Patients ◽  
Junction Protein ◽  
Type 2 Diabetic

For centuries, Berberine has been used in the treatment of enteritis in China, and it is also known to have anti-hyperglycemic effects in type 2 diabetic patients. However, as Berberine is insoluble and rarely absorbed in gastrointestinal tract, the mechanism by which it works is unclear. We hypothesized that it may act locally by ameliorating intestinal barrier abnormalities and endotoxemia. A high-fat diet combined with low-dose streptozotocin was used to induce type 2 diabetes in male Sprague Dawley rats. Berberine (100 mg/kg) was administered by lavage to diabetic rats for 2 weeks and saline was given to controls. Hyperinsulinemia and insulin resistance improved in the Berberine group, although there was no significant decrease in blood glucose. Berberine treatment also led to a notable restoration of intestinal villi/mucosa structure and less infiltration of inflammatory cells, along with a decrease in plasma lipopolysaccharide (LPS) level. Tight junction protein zonula occludens 1 (ZO1) was also decreased in diabetic rats but was restored by Berberine treatment. Glutamine-induced glucagon-like peptide 2 (GLP2) secretion from ileal tissue decreased dramatically in the diabetic group but was restored by Berberine treatment. Fasting insulin, insulin resistance index, plasma LPS level, and ZO1 expression were significantly correlated with GLP2 level. In type 2 diabetic rats, Berberine treatment not only augments GLP2 secretion and improves diabetes but is also effective in repairing the damaged intestinal mucosa, restoring intestinal permeability, and improving endotoxemia. Whether these effects are mechanistically related will require further studies, but they certainly support the hypothesis that Berberine acts via modulation of intestinal function.

scholarly journals Comparative Study of the Effects of GLP1 Analog and SGLT2 Inhibitor against Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

Biomedicines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 43 ◽  
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Medhat Taha ◽  
Rami M. Elshazli ◽  
Raouf Fekry Bedir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Caspase 3 ◽  
Sglt2 Inhibitor ◽  
Diabetic Rats ◽  
Tnf Α ◽  
Cardioprotective Effects ◽  
Underlying Mechanisms ◽  
Type 2 Diabetic

The present study investigated the possible cardioprotective effects of GLP1 and SGLT2i against diabetic cardiomyopathy (DCM) in type 2 diabetic rats and the possible underlying mechanisms. Methods: Thirty-two male Sprague Dawley rats were randomly subdivided into 4 equal groups: (a) control group, (b) DM group, type 2 diabetic rats with saline daily for 4 weeks, (c) DM + GLP1, as DM group with GLP1 analogue (liraglutide) at a dose of 75 µg/kg for 4 weeks, and (d) DM + SGLT2i as DM group with SGLT2 inhibitor (dapagliflozin) at a dose of 1 mg/kg for 4 weeks. By the end of treatment (4 weeks), serum blood glucose, homeostasis model assessment insulin resistance (HOMA-IR), insulin, and cardiac enzymes (LDH, CK-MB) were measured. Also, the cardiac histopathology, myocardial oxidative stress markers (malondialdehyde (MDA), glutathione (GSH) and CAT) and norepinephrine (NE), myocardial fibrosis, the expression of caspase-3, TGF-β, TNF-α, and tyrosine hydroxylase (TH) in myocardial tissues were measured. Results: T2DM caused significant increase in serum glucose, HOMA-IR, serum CK-MB, and LDH (p < 0.05). Also, DM caused significant myocardial damage and fibrosis; elevation of myocardial MDA; NE with upregulation of myocardial caspase-3, TNF-α, TGF-β, and TH; and significant decrease in serum insulin and myocardial GSH and CAT (p < 0.05). Administration of either GLP1 analog or SGLT2i caused a significant improvement in all studied parameters (p < 0.05). Conclusion: We concluded that both GLP1 and SGLT2i exhibited cardioprotective effects against DCM in T2DM, with the upper hand for SGLT2i. This might be due to attenuation of fibrosis, oxidative stress, apoptosis (caspase-3), sympathetic nerve activity, and inflammatory cytokines (TNF-α and TGF-β).

scholarly journals Artesunate Combined With Metformin Ameliorate on Diabetes-Induced Xerostomia by Mitigating Superior Salivatory Nucleus and Salivary Glands Injury in Type 2 Diabetic Rats via the PI3K/AKT Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Siqin Zhang ◽  
Jiarui Li ◽  
Xiaolin Nong ◽  
Yuxiang Zhan ◽  
Jiazhi Xu ◽  
...  
Keyword(s):  
Urine Volume ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Akt Pathway ◽  
Control Group ◽  
Sprague Dawley ◽  
Bdnf Expression ◽  
Parasympathetic Innervation

Polydipsia and xerostomia are the most common complications that seriously affect oral health in patients with diabetes. However, to date, there is no effective treatment for diabetic xerostomia. Recent studies have reported that artesunate (ART) and metformin (Met) improve salivary gland (SG) hypofunction in murine Sjögren’s syndrome. Therefore, aim of this study was to investigate the effect and underlying mechanism of artesunate (ART) alone and in combination with metformin (Met) on hyposalivation in type 2 diabetes mellitus (T2DM) rats. T2DM rats were induced using a high-fat diet and streptozotocin. SPF male Sprague–Dawley rats were divided into the following five groups: normal control group, untreated diabetic group, ART-treated diabetic group (50 mg/kg), Met-treated diabetic group (150 mg/kg), and ART/Met co-treated diabetic group (50 mg/kg ART and 150 mg/kg Met). ART and Met were intragastrically administered daily for 4 weeks. The general conditions, diabetes parameters and serum lipids were evaluated after drug treatment. Furthermore, we observed changes in the central superior salivatory nucleus (SSN) and SG, and changes in the AQP5 expression, parasympathetic innervation (AChE and BDNF expression), and PI3K/AKT pathway- (p-AKT, and p-PI3K), apoptosis- (Bax, Bcl-2, and Caspase3), and autophagy- (LC3 and P62) related markers expression in T2DM rats after treatment. Our results showed that ART or Met alone and ART/Met combination attenuated a range of diabetic symptoms, including weight loss, urine volume increase, water consumption increase, hyperglycemia, insulin resistance, glucose intolerance and dyslipidemia. More importantly, we found that these three treatments, especially ART/Met combination, mitigated hyposalivation in the T2DM rats via improving the central SSN and SGs damage in hyperglycemia. Our data also indicated that ART/Met attenuated SG damage though regulating the PI3K/Akt pathway to inhibit apoptosis and autophagy of SGs in the T2DM rats. Moreover, ART/Met preserved parasympathetic innervation (AChE and BDNF expression) in SGs to alleviate diabetes-induced hyposalivation likely through rescuing central SSN damage. Taken together, these findings might provide a novel rationale and treatment strategy for future treatment of diabetes-induced xerostomia in the clinic.

scholarly journals Morphological Changes and Increased Sucrase and Isomaltase Activity in Small Intestines of Insulin-Deficient and Type 2 Diabetic Rats

2003 ◽  
Vol 50 (3) ◽  
pp. 271-279 ◽  
Author(s):  
TETSUYA ADACHI ◽  
CHISATO MORI ◽  
KENICHI SAKURAI ◽  
NOBUYUKI SHIHARA ◽  
KINSUKE TSUDA ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Diabetic Rats ◽  
Small Intestines ◽  
Type 2 Diabetic

scholarly journals Metformin Ameliorates Podocyte Damage by Restoring Renal Tissue Podocalyxin Expression in Type 2 Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Limin Zhai ◽  
Junfei Gu ◽  
Di Yang ◽  
Wei Wang ◽  
Shandong Ye
Keyword(s):  
High Fat Diet ◽  
Dose Dependence ◽  
Renal Tissue ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Podocyte Damage ◽  
Sd Rats ◽  
Type 2 Diabetic ◽  
Different Doses

Podocalyxin (PCX) is a signature molecule of the glomerular podocyte and of maintaining integrity of filtration function of glomerulus. The aim of this study was to observe the effect of different doses of metformin on renal tissue PCX expression in type 2 diabetic rats and clarify its protection on glomerular podocytes. Type 2 diabetic Sprague-Dawley (SD) rats in which diabetes was induced by high-fat diet/streptozotocin (HFD-STZ) were treated with different doses of metformin (150, 300, and 500 mg/kg per day, resp.) for 8 weeks. Various biochemical parameters, kidney histopathology, and renal tissue PCX expression levels were examined. In type 2 diabetic rats, severe hyperglycemia and hyperlipidemia were developed. Urinary albumin and PCX were markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, protein and mRNA expression of renal tissue PCX were highly decreased. However, treatment of rats with different doses of metformin restored all these changes to a varying degree. These results suggested that metformin can ameliorate glomerular podocyte damage in type 2 diabetic rats, which may be partly associated with its role in restoring PCX expression and inhibiting urinary excretion of PCX with dose dependence.

scholarly journals Administration of a Decoction of Sucrose- and Polysaccharide-Rich Radix Astragali (Huang Qi) Ameliorated Insulin Resistance and Fatty Liver but Affected Beta-Cell Function in Type 2 Diabetic Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Yi-Chen Juan ◽  
Yao-Haur Kuo ◽  
Chia-Chuan Chang ◽  
Li-Jie Zhang ◽  
Yan-Yu Lin ◽  
...  
Keyword(s):  
Beta Cell ◽  
Fatty Liver ◽  
Beta Cell Function ◽  
Cell Function ◽  
Body Weight Loss ◽  
Diabetic Rats ◽  
Radix Astragali ◽  
Sprague Dawley ◽  
Type 2 Diabetic

The current investigation attempted to confirm the beneficial actions of a chemically characterized Radix Astragali decoction (AM-W) against type 2 diabetic (T2D) Sprague-Dawley (SD) rats. Using a case/control design, after 2 months of treatment with AM-W (500 mg/kg, daily i.p.) in T2D rats therapeutic outcomes were compared. Sucrose andAstragaluspolysaccharides (ASPs) were shown to exist in nearly equal proportions in AM-W. Body weight loss, an improvement in insulin sensitivity, and an attenuation of fatty liver after AM-W administration in T2D rats were evident. Surprisingly, blood sugar, beta-cell function, and glucose tolerance in T2D rats did not improve with AM-W treatment. Further investigation indicated the deleterious effects of the addition of sucrose (100 and 500 μg/mL) and APSs (500 μg/mL) on glucose-stimulated insulin secretion and viability, respectively. In conclusion, a proper administration dosage and a reduction in the sucrose content are keys to maximizing the merits of this herb.

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