scholarly journals Ethanolic Extract of Centella asiatica Treatment in the Early Stage of Hyperglycemia Condition Inhibits Glomerular Injury and Vascular Remodeling in Diabetic Rat Model

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Wiwit A. W. Setyaningsih ◽  
Nur Arfian ◽  
Akbar S. Fitriawan ◽  
Ratih Yuniartha ◽  
Dwi C. R. Sari
Keyword(s):  
Diabetes Mellitus ◽  
Vascular Injury ◽  
Rat Model ◽  
Vascular Remodeling ◽  
Kidney Diseases ◽  
Early Stage ◽  
Vascular Dysfunction ◽  
Centella Asiatica ◽  
Control Group ◽  
Glomerular Injury

Background. Diabetes mellitus (DM) is marked by oxidative stress, inflammation, and vascular dysfunction that caused diabetic nephropathy that resulted in end-stage renal disease (ESRD). Vascular dysfunction is characterized by an imbalance in vasoconstrictor and vasodilator agents which underlies the mechanism of vascular injury in DM. Additionally, diminished podocytes correlate with the severity of kidney injury. Podocyturia often precedes proteinuria in several kidney diseases, including diabetic kidney disease. Centella asiatica (CeA) is known as an anti-inflammatory and antioxidant and has neuroprotective effects. This research aimed to investigate the potential effect of CeA to inhibit glomerular injury and vascular remodeling in DM. Methods. The DM rat model was induced through intraperitoneal injection of streptozotocin 60 mg/kg body weight (BW), and then rats were divided into 1-month DM (DM1, n = 5), 2-month DM (DM2, n = 5), early DM concurrent with CeA treatment for 2 months (DMC2, n = 5), and 1-month DM treated with CeA for 1-month (DM1C1, n = 5). The CeA (400 mg/kg BW) was given daily via oral gavage. The control group (Control, n = 5) was maintained for 2 months. Finally, rats were euthanized and kidneys were harvested to assess vascular remodeling using Sirius Red staining and the mRNA expression of superoxide dismutase, podocytes marker, ACE2, eNOS, and ppET-1 using RT-PCR. Results. The DM groups demonstrated significant elevation of glucose level, glomerulosclerosis, and proteinuria. A significant reduction of SOD1 and SOD3 promotes the downregulation of nephrin and upregulation of TRPC6 mRNA expressions in rat glomerular kidney. Besides, this condition enhanced ppET-1 and inhibited eNOS and ACE2 mRNA expressions that lead to the development of vascular remodeling marked by an increase of wall thickness, and lumen wall area ratio (LWAR). Treatment of CeA, especially the DMC2 group, attenuated glomerular injury and showed the reversal of induced conditions. Conclusions. Centella asiatica treatment at the early stage of diabetes mellitus ameliorates glomerulosclerosis and vascular injury via increasing antioxidant enzymes.

scholarly journals Early identification of tubulointerstitial renal injury in hypertensive patients: a comparative evaluation of the urine biomarkers NGAL and KIM 1

2019 ◽  
Vol 25 (4) ◽  
pp. 407-415
Author(s):  
O. B. Kuzmin ◽  
V. V. Zhezha ◽  
D. N. Begun ◽  
V. A. Tsareva ◽  
T. G. Gubanova
Keyword(s):  
Diabetes Mellitus ◽  
Renal Dysfunction ◽  
Kidney Function ◽  
Kidney Diseases ◽  
Early Stage ◽  
Control Group ◽  
Ngal Level ◽  
Urine Ngal ◽  
Tubulointerstitial Injury ◽  
Reduced Kidney Function

Objective. The aim of the study was a comparative assessment of urine NGAL (neutrophil gelatinase associated lipocalin) and KIM‑1 (kidney injury molecule‑1) as biomarkers of early detection of tubulointerstitial renal damage in patients with arterial hypertension (HTN) without concomitant diabetes mellitus and kidney disease.Design and methods. The study involved 52 patients of both sexes (17 man and 35 women, mean age 60,2 ± 6,54 years) hospitalized for aggravation of HTN 1–3 degrees, which were divided into 3 groups with glomerular filtration rate (GFR) > 90 ml/min/1,73 m 2 (n = 21), 60–90 ml/min/1,73 m 2 (n = 19) and < 60 ml/min/1,73 m 2 (n = 12). In a separate group, patients with albuminuria in the range 10–29 mg/g urine creatinine were isolated. The comparison group consisted of 15 normotensive individuals (6 men and 9 women, mean age 49,8 ± 9,68 years) with no obvious signs of renal, cardiovascular or other diseases. All patients and controls underwent examination, and albumin, NGAL (Human NGAL ELISA kit) and KIM‑1 (Human KIM‑1 Immunoassay ELISA) levels were assessed in the first morning urine portion.Results. In the group of patients with GFR 67,7 ± 4,92 ml/min/1,73 m 2 (mildly reduced kidney function) and in the group of patients with GFR 55,8 ± 4,44 ml/min/1,73 m 2 (renal dysfunction) urine NGAL level increased by 3,43 (р < 0,05) and 3,92 times (р < 0,05), respectively, as compared with the control group. The urine concentration of KIM‑1 increased by 2,06 times (р < 0,05) was observed only in patients with renal dysfunction. Based on the ROC analysis AUC for the urine NGAL level in patients with mildly reduced kidney function is 0,78 (95 % confidence interval, 95 %CI: 0,70–0,86; p < 0,001), specificity — 89,6 %, sensitivity — 66,7 %. Similar indicators for KIM‑1 are 0,72 (95 % CI: 0,64–0,80; p < 0,001), specificity — 85,3 %, sensitivity — 16,7 %. In the group of patients with mildly reduced kidney function the urine level of NGAL correlated with the HTN severity (r = 0,8944, р < 0,001) and its duration (r = 0,8953, р < 0,001).Conclusions. Urine NGAL as compared with KIM‑1 is a more sensitive biomarker, which indicates tubulointerstitial injury in HTN patients without diabetes mellitus and kidney diseases in the early stage of impairment renal function.

scholarly journals Effect of Everolimus versus Bone Marrow-Derived Stem Cells on Glomerular Injury in a Rat Model of Glomerulonephritis: A Preventive, Predictive and Personalized Implication

2021 ◽  
Vol 23 (1) ◽  
pp. 344
Author(s):  
Mohamed M. Zedan ◽  
Ahmed K. Mansour ◽  
Ashraf A. Bakr ◽  
Mohamed A. Sobh ◽  
Hesam Khodadadi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Adverse Effects ◽  
Rat Model ◽  
Inflammatory Responses ◽  
Early Stage ◽  
Control Group ◽  
Glomerular Mesangial Cells ◽  
Glomerular Injury ◽  
Endothelial Repair

Glomerular endothelial injury and effectiveness of glomerular endothelial repair play a crucial role in the progression of glomerulonephritis. Although the potent immune suppressive everolimus is increasingly used in renal transplant patients, adverse effects of its chronic use have been reported clinically in human glomerulonephritis and experimental renal disease. Recent studies suggest that progenitor stem cells could enhance glomerular endothelial repair with minimal adverse effects. Increasing evidence supports the notion that stem cell therapy and regenerative medicine can be effectively used in pathological conditions within the predictive, preventive and personalized medicine (PPPM) paradigm. In this study, using an experimental model of glomerulonephritis, we tested whether bone marrow-derived stem cells (BMDSCs) could provide better effect over everolimus in attenuating glomerular injury and improving the repair process in a rat model of glomerulonephritis. Anti-Thy1 glomerulonephritis was induced in male Sprague Dawley rats by injection of an antibody against Thy1, which is mainly expressed on glomerular mesangial cells. Additional groups of rats were treated with the immunosuppressant everolimus daily after the injection of anti-Thy1 or injected with single bolus dose of BMDSCs after one week of injection of anti-Thy1 (n = 6–8). Nine days after injection of anti-Thy1, glomerular albumin permeability and albuminuria were significantly increased when compared to control group (p < 0.05). Compared to BMDSCs, everolimus was significantly effective in attenuating glomerular injury, nephrinuria and podocalyxin excretion levels as well as in reducing inflammatory responses and apoptosis. Our findings suggest that bolus injection of BMDSCs fails to improve glomerular injury whereas everolimus slows the progression of glomerular injury in Anti-Thy-1 induced glomerulonephritis. Thus, everolimus could be used at the early stage of glomerulonephritis, suggesting potential implications of PPPM in the treatment of progressive renal injury.

scholarly journals Oral and Topical Centella asiatica in Type 2 Diabetes Mellitus Patients with Dry Skin: A Three-Arm Prospective Randomized Double-Blind Controlled Trial

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Lili Legiawati ◽  
Kusmarinah Bramono ◽  
Wresti Indriatmi ◽  
Em Yunir ◽  
Siti Setiati ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Centella Asiatica ◽  
Control Group ◽  
Dry Skin ◽  
Sod Activity ◽  
Double Blind

Introduction. Uncontrolled diabetes mellitus (DM) is related to skin disorders, particularly dry skin. Pathogenesis of dry skin in type 2 diabetes mellitus (T2DM) rises from the chronic hyperglycemia causing an increase in advanced glycation end-products (AGEs), proinflammatory cytokines, and oxidative stress. Combination of oral and topical Centella asiatica (CA) is expected to treat dry skin in T2DM patients more effectively through decreasing N(6)-carboxymethyl-lysine (CML) and interleukin-1α (IL-1α) and increasing superoxide dismutase (SOD) activity. Methods. A three-arm prospective, double-blind, randomized, controlled study was performed to evaluate the efficacy of the oral and topical CA extract in 159 T2DM patients with dry skin. The subjects were divided into the CA oral (CAo) 2 × 1.100 mg + CA topical (CAt) 1% ointment group, oral placebo (Plo) + CAt group, and Plo and topical placebo (Plt) group. Dry skin assessment was performed on day 1, 15, and 29, while evaluation of CML, IL-1α, and SOD activity was on day 1 and 29. Result. Effectivity of CAo + CAt combination was assessed based on HbA1c and random blood glucose (RBG). In well-controlled blood glucose, on day 29, the percentage of SRRC decrement was greater in the CAo + CAt group compared to the control group (p=0.04). SCap value in the CAo + CAt group was greater than that in the control group (p=0.01). In the partially controlled blood glucose, increment of SOD activity in the CAo + CAt group was greater than that in the control group (p=0.01). There were medium-to-strong correlation between CML with SOD (r = 0.58, p<0.05) and IL-1α with SOD (r = 0.70, p<0.05) in well-controlled blood glucose. Systemic and topical adverse events were not significantly different between groups. Conclusion. CAo and CAt combination can be used to significantly improve dry skin condition through increasing SOD activity in T2DM patients with controlled blood glucose.

scholarly journals Anti-Inflammatory Effect of Centella asiatica (L.) Extract by Decreasing TNF-α Serum Levels in Rat Model of Traumatic Brain Injury

2021 ◽  
Vol 53 (2) ◽  
Author(s):  
Nafiisah Nafiisah ◽  
◽  
Falah Faniyah ◽  
Yoga Mulia Pratama
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Rat Model ◽  
Alternative Therapy ◽  
Centella Asiatica ◽  
Serum Levels ◽  
Control Group ◽  
Inflammatory Reactions ◽  
Experimental Animals ◽  
Tnf Α

Centella asiatica (L.) has many active ingredients with many important roles, including as antioxidant, anti-inflamation and neuroprotectant. Centella asiatica (L.) can reduce inflammatory reactions by inhibiting the activity of TNF-α. Thus, Centella asiatica (L.) is a potential alternative therapy for traumatic brain injury by reducing inflammation via TNF-α expression modulation. This study aimed to determine the effect of Centella asiatica (L.) on serum TNF-α levels in rat model of traumatic brain injury. This study was conducted during the period of July 3-17, 2020 at the LPPT Unit IV, Gajah Mada University. This was a true experimental with post-test only control group study on 35 male wistar rats as the experimental animals. The rats were divided into 5 groups: P1, P2, and traumatic brain injury groups that received Centella asiatica (L.) treatement at 150, 300, and 600mg/kgBW/d doses, respectively. Blood samples were collected after the experimental animals were terminated to assess serum TNF-α levels. Mean TNF-α levels were 60,980±4,057, 76,931±0,698, P3=75,889±0,948, P4=75,868±1,163, and 74,508±1,126 for P1, P2, P3, P4, and P5, respectively. The Kruskal Wallis test results showed a statistically different between groups (p = 0.005). This study shows that Centella asiatica (L.) can decrease serum TNF-α level in rat model of traumatic brain injury.

Renoprotective effects of long-term oral nicotine in a rat model of spontaneous proteinuria

2012 ◽  
Vol 302 (7) ◽  
pp. F895-F904 ◽  
Author(s):  
Pramod K. Agarwal ◽  
Jacob van den Born ◽  
Harry van Goor ◽  
Gerjan Navis ◽  
Rijk O. B. Gans ◽  
...  
Keyword(s):  
Rat Model ◽  
Structural Damage ◽  
Kidney Diseases ◽  
Blood Pressure Reduction ◽  
Renal Diseases ◽  
Control Group ◽  
Renal Inflammation ◽  
Anti Inflammatory ◽  
Oral Nicotine

Many proteinuric renal conditions are accompanied by renal inflammation. Nicotine is known to have anti-inflammatory properties and is used in oral form to help subjects quit smoking. A potential anti-inflammatory role of nicotine in proteinuric renal diseases has not been investigated to date. We therefore evaluated the effects of oral nicotine in a rat model of proteinuria-induced renal inflammation. We used a well-established model of adult (24 wk of age) male Munich-Wistar-Frömter rats. Animals were given three different physiological doses of nicotine in drinking water for 28 wk until 52 wk of age (long term). A group without nicotine served as a parallel control. At 52 wk of age, the control group had a 2.1 times reduction in creatinine clearance, 3.2 times increase in urinary protein excretion, an increased focal glomerulosclerosis (FGS) score, increased glomerular desmin deposition, decreased glomerular podocin, and a higher accumulation of macrophages and myofibroblasts compared with 24-wk-old animals. Oral treatment with nicotine dose dependently preserved renal function and halted proteinuria progression, which were independent of blood pressure reduction. It also reduced FGS, desmin deposition, podocin loss, and density of renal macrophages and myofibroblasts. Nicotine also reduced the level of gene expression of the renal inflammatory markers monocyte chemoattractant protein and vascular cell adhesion molecule-1. In conclusion, long-term oral nicotine preserved kidney function, reduced proteinuria, reduced renal inflammation, and protected progression of renal structural damage in a rat model of proteinuria. We further suggest evaluating nicotine as a potential additional therapeutic option for treating proteinuric kidney diseases.

Abstract 192: Activation of Kidney Renin-angiotensin System (RAS) and Renoprotective Effects of Direct Renin Inhibition (DRI) in Glomerulonephritis

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Kayoko Miyata ◽  
Ryousuke Satou ◽  
Akemi Sato ◽  
Dale Seth ◽  
Allison Davis ◽  
...  
Keyword(s):  
Kidney Diseases ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Left Ventricular ◽  
Control Group ◽  
Mrna Levels ◽  
Ang Ii ◽  
Glomerular Injury ◽  
Plasma Angiotensin ◽  
Intrarenal Ras

The development of glomerulonephritis causes glomerular injury and reduced renal function and is associated with increased renin release. The aims of this study were to demonstrate activation of intrarenal RAS in glomerulonephritis and determine the effects of DRI with aliskiren on progression of glomerulonephritis associated renal injury induced by administration of an anti-Thy1.1 antibody. We divided rats into 3 groups; control group, anti-Thy1.1 glomerulonephritis group and anti-Thy1.1 glomerulonephritis treated with aliskiren (30 mg/kg/day) group. In the anti-Thy1.1 rats, protein excretion and micro albumin excretion levels increased markedly after anti-Thy1.1 antibody injection. The increases in protein (94.7 ± 13.0 mg/day) and micro albumin (7.5 ± 2.6 mg/day) excretions were attenuated by aliskiren treatment (43.6 ± 4.5 mg/day of protein and 2.6 ± 0.7 mg/day of micro albumin). The glomerular expansion score was significantly higher in the anti-Thy1.1 group compared to the control group. The anti-Thy1.1 group also showed elevation of intrarenal TGF-β and PAI-1 mRNA levels compared with control rats. The progression of glomerular expansion and elevation of these mRNA levels was prevented by aliskiren. Importantly, the anti-Thy1.1 group had markedly increased urinary angiotensinogen (AGT) excretion at days 3 (3102.9 ± 683.8 ng/day), but these changes were markedly suppressed by aliskiren treatment (441.3 ± 104.8 ng/day). AGT protein expression in the kidney was significantly lower in the aliskiren treatment group compared with anti-Thy1.1 group (western blot, 0.8 ± 0.04 and immunohistochemistry, 0.7 ± 0.11 relative to anti-Thy1.1 group). Furthermore, plasma renin activity (PRA) and plasma angiotensin (Ang) II levels were significantly increased in the anti-Thy1.1 group and aliskiren treatment prevented the elevation of PRA and plasma Ang II. Anti-Thy1.1 antibody also elicited left ventricular hypertrophy and fibrosis, which were not ameliorated by aliskiren. These results demonstrate that DRI prevents or reduces intrarenal RAS activation and glomerular injury in progressive glomerulonephritis. Accordingly, DRI may be an effective approach to treat glomerulonephritis as well as other intrarenal RAS associated kidney diseases.

Angiotensin-(1-7) improves Islet Function in a Rat Model of Streptozotocin-induced Diabetes Mellitus by Up-regulating the Expression of Pdx1/Glut2

2020 ◽  
Vol 20 ◽  
Author(s):  
Jingjing Li ◽  
Ruifang Zhu ◽  
Yalin Liu ◽  
Jinhui Yang ◽  
Xiaoyan Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Blood Glucose ◽  
Rat Model ◽  
Control Group ◽  
Standard Diet ◽  
Islet Function ◽  
Model Assessment ◽  
Glucose Transporter 2 ◽  
Streptozotocin Induced Diabetes

Objective: To observe the effects of angiotensin-(1-7) (Ang-(1-7)) on glucose metabolism, islet function and insulin resistance in a rat model of streptozotocin-induced diabetes mellitus (DM) and investigate its mechanism. Method: Thirty-four male Wistar rats were randomly divided into 3 groups: control group, which was fed standard diet, DM group, high-fat diet and injected with streptozotocin, and Ang-(1-7) group receiving injection of streptozotocin followed by Ang-(1-7) treatment. Blood glucose level, fasting serum Ang II and insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. The pancreases were collected for histological examination, protein and gene expressions analysis. Results: Compared with control group, fasting blood glucose, serum angiotensin II level, and HOMA-IR value increased, while serum insulin level decreased in DM group. Moreover, islet structure was damaged, β cells were irregularly arranged, the cytoplasm was loose in DM group. Expressions of Pancreatic duodenal homeobox-1 (Pdx1), glucose transporter-2 (Glut2) and glucokinase (Gk) were significantly decreased in DM group compared with control group. However, the DMassociated changes were dramatically reversed following Ang-(1-7) treatment. Conclusion: Ang-(1-7) protects against streptozotocin-induced DM through the improvement of insulin secretion, insulin resistance and islet fibrosis, which is associated with the upregulation of Pdx1, Glut2 and Gk expressions.

scholarly journals The Biological Impacts of Sitagliptin on the Pancreas of a Rat Model of Type 2 Diabetes Mellitus: Drug Interactions with Metformin

Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 6 ◽  
Author(s):  
Lamiaa M. Shawky ◽  
Ahmed A. Morsi ◽  
Eman El Bana ◽  
Safaa Masoud Hanafy
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model ◽  
Cell Damage ◽  
Diabetic Rats ◽  
Male Rats ◽  
Control Group ◽  
Dipeptidyl Peptidase 4

Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a beneficial class of antidiabetic drugs. However, a major debate about the risk of developing pancreatitis is still existing. The aim of the work was to study the histological and immunohistochemical effects of sitagliptin on both endocrine and exocrine pancreases in a rat model of type 2 diabetes mellitus and to correlate these effects with the biochemical findings. Moreover, a possible synergistic effect of sitagliptin, in combination with metformin, was also evaluated. Fifty adult male rats were used and assigned into five equal groups. Group 1 served as control. Group 2 comprised of untreated diabetic rats. Group 3 diabetic rats received sitagliptin. Group 4 diabetic rats received metformin. Group 5 diabetic rats received both combined. Treatments were given for 4 weeks after the induction of diabetes. Blood samples were collected for biochemical assay before the sacrification of rats. Pancreases were removed, weighed, and were processed for histological and immunohistochemical examination. In the untreated diabetic group, the islets appeared shrunken with disturbed architecture and abnormal immunohistochemical reactions for insulin, caspase-3, and inducible nitric oxide synthase (iNOS). The biochemical findings were also disturbed. Morphometrically, there was a significant decrease in the islet size and islet number. Treatment with sitagliptin, metformin, and their combination showed an improvement, with the best response in the combined approach. No evidence of pancreatic injury was identified in the sitagliptin-treated groups. In conclusion, sitagliptin had a cytoprotective effect on beta-cell damage. Furthermore, the data didn’t indicate any detrimental effects of sitagliptin on the exocrine pancreas.

scholarly journals The Сharacter and Development of photoreceptors photodegeneration combined with alloxan diabetes

2002 ◽  
Vol 1 (2) ◽  
pp. 47-52
Author(s):  
S. V. Logvinov ◽  
E. Yu. Varakuta ◽  
A. V. Potapov
Keyword(s):  
Diabetes Mellitus ◽  
Alloxan Diabetes ◽  
Light Exposure ◽  
Early Stage ◽  
Male Rats ◽  
Control Group ◽  
Group 3 ◽  
Group 2 ◽  
Alloxan Injection ◽  
Group 1

The aim of the research is to determine the character and development of a alterations in photoreceptors, caused by high-intensity light on the early stage of diabetes mellitus. The methods of light and electron microscopy were used. Experiments were obtained from 80 adult white male rats. The rats of group 1 (n = 20) received 1 injection of alloxan (15 mg per 100 g of weight) in order to model diabetes mellitus. The rats of group 2 (n = 20) were exposed for light of luminecent LB-40 lamps (6000 lx) for 6 hours. The rats of group 3 (n = 20) were exposed to the light with the same parameters 1 month after alloxan injection. The last 20 rats made a control group 4. The rats groups 2 and 3 were sacrifised by decapitation 1, 7, 14, 30 days after the light exposure, the rats of group 1 on the 4, 5, 6, 8 week after the alloxan injection. Light exposure combined with diabetes causes destruction pigment epithelium inner and outer processed of photoreceptors followed by pyknosis of nucleus and replacement by vacial glia. On the 7th day after the exposure local disappearance of according retinal layers was obsevred. In these local sites of the most intensive destruction in group 3 there is 1,6 times more cells with caryopyknosis from in according sites of group 2 (just light exposure) rats. Thus, alloxan diabetes on the early stage of its development (1 month) intensifies light damage of retinal photoreceptors. Probably, increase of oxydative processes and antioxidative systems break down play an important role in this synergetic effect.

scholarly journals A Hypercaloric Diet Induces Early Podocyte Damage in Aged, Non-Diabetic Rats

2021 ◽  
Vol 55 (S4) ◽  
pp. 96-112
Keyword(s):  
Metabolic Syndrome ◽  
Immune Cell ◽  
Kidney Diseases ◽  
Visceral Obesity ◽  
Control Group ◽  
Aged Rats ◽  
Glomerular Injury ◽  
Nestin Expression ◽  
Podocyte Damage ◽  
Number Of Patients

Background/Aims: The number of patients of older age with metabolic syndrome, obesity, and associated kidney disease, which is characterized by podocyte damage, glomerular hypertrophy, and focal segmental glomerulosclerosis (FSGS), is increasing worldwide. Animal models that would reflect the development of such kidney diseases could facilitate the testing of drugs. We investigated the renal effects of a long-term high caloric diet in aged rats and the potential effects of drugs used to treat metabolic syndrome. Methods: We analyzed nine-month-old male and female Sprague Dawley rats fed five months with a normal diet (control group) or high-fat-high-carbohydrate diet (HFHCD group). Two additional groups were fed with HFHCD and treated with drugs used in patients with metabolic syndrome, i.e., the glucagon-like peptide receptor 1 agonist liraglutide (HFHCD+liraglutide group) or metformin (HFHCD+metformin group). Results: Except an increase of waist circumference as a sign of visceral obesity, the HFHCD diet did not induce metabolic syndrome or obesity. There were no significant changes in kidney function and all groups showed similar indices of glomerular injury, i.e., no differences in glomerular size or the number of glomeruli with FSGS or with FSGS-precursor lesions quantified by CD44 expression as a marker of parietal epithelial cell (PEC) activation. Analysis of ultrastructural morphology revealed mild podocyte stress and a decrease of glomerular nestin expression in the HFHCD group, whereas podocin and desmin were not altered. HFHCD did not promote fibrogenesis, however, treatment with liraglutide led to a slightly increased tubulointerstitial damage, immune cell infiltration, and collagen IV expression compared to the control and HFHCD groups. Conclusion: A five-month feeding with HFHCD in aged rats induced mild podocyte injury and microinflammation, which was not alleviated by liraglutide or metformin.

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