Metformin protects against diabetes–induced heart injury and dunning prostate cancer model

2020 ◽  
pp. 096032712094745
Author(s):  
BB Bayrak ◽  
P Koroglu ◽  
O Karabulut Bulan ◽  
R Yanardag

In this study, both diabetes and Dunning prostate cancer were induced for the first time in Copenhagen rats in vivo. Thus, the effects of metformin against heart tissue damage of these rats were investigated by biochemical methods. Dunning prostate cancer was induced in Copenhagen rats using high metastatic MAT-LyLu cells. The rats were divided as follows: Control group: only injected with 0.9% NaCl for 14 days; Diabetic group: only injected single dose of streptozotocin (STZ) (65 mg/kg); Cancer group: subcutaneously (s.c) inoculated with 2 x 104 MAT-LyLu cells only; Diabetic + cancer (DC) group: inoculated with 2 x 104 MAT-LyLu cells and STZ injection, Cancer + metformin (CM) group: injected with metformin for 14 days after Mat-LyLu cells application; Diabetic + cancer + metformin (DCM) group: metformin administered for 14 days together with STZ and Mat-LyLu cells. At the end of the experimental period, heart tissues were taken. Reduced glutathione and total antioxidant status levels in heart tissues were decreased, whereas lipid peroxidation, advanced oxidized protein products, nitric oxide, homocysteine, and reactive oxygen species levels, total oxidant status and catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and xanthine oxidase activities increased in the diabetic, cancer and DC groups. Treatment with metformin reversed these effects. In conclusion, the present study shows that metformin has a protective effect against heart tissue damage in STZ-induced diabetic rats with Dunning prostate cancer.

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Veysel Kenan Çelık ◽  
Zeynep Deniz Şahın ◽  
İsmail Sari ◽  
Sevtap Bakir

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.


2012 ◽  
Vol 7 (10) ◽  
pp. 1934578X1200701 ◽  
Author(s):  
Ciddi Veeresham ◽  
Samala Sujatha ◽  
Thatipamula Sandya Rani

The effect of piperine on the pharmacokinetics and pharmacodynamics of glimepiride in normal as well as diabetic rats was studied. In normal and streptozotocin induced diabetic rats the combination of glimepiride with piperine increased all the pharmacokinetic parameters, such as Cmax, AUC0-n, AUCtotal, t½, and MRT, and decreased the clearance, Vd, markedly as compared with the control group. In pharmacodynamic studies, the combination of glimepiride with piperine provided significant protection against the diabetes induced alterations in the biochemical parameters. In addition, the combination of glimepiride with piperine also improved the total antioxidant status significantly in diabetic rats compared with piperine and glimepiride treated groups. The results revealed that a combination of glimepiride with piperine led to the enhancement of the bioavailability of glimepiride by inhibiting the CYP2C9 enzyme, which suggested that piperine might be beneficial as an adjuvant to glimepiride in a proper dose, in diabetic patients.


2018 ◽  
Vol 19 (3) ◽  
pp. 287-291 ◽  
Author(s):  
Ashish Verma ◽  
Vivek Tripathi ◽  
Sahib T Singh ◽  
Chetan D Singh ◽  
Jaspreet S Gill

ABSTRACT Introduction Periodontitis is a common problem affecting a significant population of the world. For the assessment of oxidative stress of an individual, total oxidation status (TOS) and total antioxidant capacity (TAOC) are the significant biomarkers. Hence, we planned the present study to assess malondialdehyde (MDA), TOS, TAOC levels, and oxidative stress index (OSI) in generalized aggressive periodontitis (GP) and chronic periodontitis (CP) patients. Materials and methods The present study included assessment of 40 CP patients, 40 GP patients, and 40 healthy controls. Clinical assessment of all the subjects was done by measuring the probing depth (PD), clinical attachment (CL), gingival index (GI), gingival bleeding index (GBI), and plaque index (PI). Salivary and serum samples were taken and assessed by standard procedures as described previously in the literature. All the values were assessed and compared. Results Significant results were obtained while comparing all the periodontal parameters in between various study groups. Mean serum MDA levels in the CP, GP, and control group were found to be 0.68, 0.65, and 0.61 µM respectively. Statistically nonsignificant results were obtained while comparing the serum MDA levels in between the three study groups. Significant results were obtained while comparing the mean serum and salivary TOS values, TAOC values, and OSI in between various study groups. Conclusion In periodontitis patients, oxidative stress was significantly higher in comparison with healthy subjects. Clinical significance Oxidative parameters do play a significant role in the pathologic profile of periodontitis. How to cite this article Tripathi V, Singh ST, Sharma V, Verma A, Singh CD, Gill JS. Assessment of Lipid Peroxidation Levels and Total Antioxidant Status in Chronic and Aggressive Periodontitis Patients: An in vivo Study. J Contemp Dent Pract 2018;19(3):287-291.


Author(s):  
Wulan Christijanti ◽  
Aditya Marianti ◽  
Wiwi Isnaeni

<p><strong>Background</strong></p><p>Diabetes mellitus is a chronic disease caused by lack of insulin production in the pancreas or by insulin resistance, the disease being characterized by elevated blood glucose levels. Hyperglycemia in diabetes could lead to oxidative stress due to the rise in 8-oxo-2'-deoxyguanosine (8-oxo-dG) levels and the decrease in levels of total antioxidant status (TAS). The purpose of this study was to assess the effect <em>Aloe vera </em>extract on 8-oxo-dG level and total antioxidant status in diabetic rat testis.</p><p><strong> </strong></p><p><strong>Methods</strong></p><p>This was an experimental laboratory study with 20 rat samples which were divided into 4 groups (1 control group and 3 treatment groups). Diabetes was induced in the rats by streptozotocin (STZ) at 65 mg/kgBW. The diabetic rats were then treated for 28 days with <em>Aloe vera</em> extract at 0 mg (P0), 200 mg rind (P1), 200 mg pulp (P2), respectively. The level of 8 -oxo-dG was measured by ELISA and total antioxidant status with 2,2' -azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS). Data were analyzed with ANOVA and Least Significant Difference Advanced Test at P&lt;0.05.</p><p><strong> </strong></p><p><strong>Results</strong></p><p>8-Oxo-dG levels were significantly different between the control group and both P0 and P2, but not between the control group and P1. Among the treatment groups the 8-oxo-dG levels were significantly different. Mean total antioxidant status was significantly different between control and treatment groups, and also between treatment groups (p&lt;0.05).</p><p><strong> </strong></p><p><strong>Conclusions</strong></p><p><em>Aloe vera</em> extract reduced free radicals (level of 8-oxo-dG) and increased the total antioxidant status in diabetic rat testis.</p><p> </p>


Author(s):  
N. N. Malyutina ◽  
A. F. Bolotova ◽  
R. B. Eremeev ◽  
A. Zh. Gilmanov ◽  
D. Yu. Sosnin

Introduction. The overwhelming number of publications contains only data on the content of individual antioxidants, but not on the overall antioxidant activity of the blood in patients with vibration disease.The aim of the study was to determine the total antioxidant activity of blood serum in patients with vibration disease.Materials and methods. Th e main group consisted of 30 people diagnosed with “Vibration disease” of 1 degree (n=21) and 2 degrees (n=9). Th e control group consisted of 30 clinically healthy men, comparable in age with the main group (p=0.66). Th e total activity of antioxidant systems of blood plasma was evaluated photometrically using the test system “Total antioxidant status-Novo” (“Vector-best”, Russia).Results. The indicator of the total antioxidant status (TAS) was 1,038±0.232 mmol/l in the examined main group, against 1,456±0.225 mmol/l in the examined control group (p<0.000001). Th e coefficient of variation (CV) in patients with vibration disease was 22.35%, 1.45 times higher than in the control group (15.45%). In the main group there was a positive correlation between age and TAS (R=0.525), in the control group there was no such relationship (R=0.095). Th e degree of decrease depended on the severity of vibration disease.Conclusions. 1. The development of vibration disease is accompanied by a decrease in the antioxidant status of blood serum. 2. Th e degree of decrease in the antioxidant status of blood serum correlates with the severity of vibration disease. 3. Reduction of TAS can serve as a pathogenetic justification of the need to include drugs and/or biologically active additives with antioxidant activity in therapy


2014 ◽  
Vol 307 (5) ◽  
pp. E447-E455 ◽  
Author(s):  
Lorenzo Glorie ◽  
Geert J. Behets ◽  
Lesley Baerts ◽  
Ingrid De Meester ◽  
Patrick C. D'Haese ◽  
...  

Dipeptidyl peptidase IV (DPP IV) modulates protein activity by removing dipeptides. DPP IV inhibitors are currently used to improve glucose tolerance in type 2 diabetes patients. DPP IV substrates not only increase insulin secretion but also affect bone metabolism. In this study, the effect of DPP IV inhibitor sitagliptin on bone was evaluated in normal and streptozotocin-induced diabetic rats. This study included 64 male Wistar rats divided into four groups ( n = 16): two diabetic and two control groups. One diabetic and one control group received sitagliptin through drinking water. Tibiae were scanned every 3 wk using an in vivo μCT scanner. After 6 and 12 wk, rats were euthanized for histomorphometric analysis of bone parameters. The mechanical resistance of femora to fracture was assessed using a three-point bending test, and serum levels of bone metabolic markers were measured. Efficient DPP IV inhibition was achieved in sitagliptin-treated groups. Trabecular bone loss, the decrease in trabecular number, and the increase in trabecular spacing was attenuated through sitagliptin treatment in diabetic rats, as shown by in vivo μCT. Bone histomorphometry was in line with these results. μCT analysis furthermore showed that sitagliptin prevented cortical bone growth stagnation in diabetic rats, resulting in stronger femora during three-point bending. Finally, the serum levels of the resorption marker CTX-I were significantly lower in sitagliptin-treated diabetic animals compared with untreated diabetic animals. In conclusion, sitagliptin treatment attenuates bone loss and increases bone strength in diabetic rats probably through the reduction of bone resorption and independent of glycemic management.


Author(s):  
KAMNI RAJPUT ◽  
RAMESH CHANDRA DUBEY

Objective: In vitro antioxidant activity, in vivo antidiabetic property and intestinal attachment by two potential probiotic bacterial strains, namely, Enterococcus faecium and Enterococcus hirae were studied using albino rats. Methods: Antioxidant the activity was assessed using 2,2-Diphenyl-1-picrylhydrazyl radicals scavenging assay. Alloxan was administered intraperitoneally to induce diabetic conditions in experimental rats. Animals were treated with oral administration of Enterococcus spp., such as E. faecium, and E. hirae isolated from goat and sheep milk. The control animal group received normal saline for the same days. Glibenclamide drug was used as a positive control against probiotic bacterial cells. Results: However, administration of probiotic bacterial strains E. faecium and E. hirae, in albino rats significantly (p<0.05) at varying doses lowered blood glucose levels in diabetic rats as compared to the diabetic control group. Both the species of Enterococcus increased the bodyweight of experimental rats. However, E. faecium was the best antidiabetic strain having the antioxidant activities also in comparison to E. hirae. The attachment of probiotic bacterial cells E. faecium on the rat’s intestine wall against pathogens was examined. Furthermore, E. faecium showed its aggregation with pathogens by attachment of the intestines of albino rats. This showed that both the bacterial strains exhibited in vivo antidiabetic effect. Conclusion: The results of this study showed that probiotic bacteria possess antioxidant, antidiabetic activities, and attachment of intestine.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xinxin Zhang ◽  
Yating Qin ◽  
Xiaoning Wan ◽  
Hao Liu ◽  
Chao Iv ◽  
...  

Purpose. Hydroxytyrosol (HT) processes multiaspect pharmacological properties such as antithrombosis and antidiabetes. The aim of this study was to explore the antistherosclerotic roles and relevant mechanisms of HT. Methods. Male apoE-/- mice were randomly divided into 2 groups: the control group and the HT group (10 mg/kg/day orally). After 16 weeks, blood tissue, heart tissue, and liver tissue were obtained to detect the atherosclerotic lesions, histological analysis, lipid parameters, and inflammation. And the underlying molecular mechanisms of HT were also studied in vivo and in vitro. Results. HT administration significantly reduced the extent of atherosclerotic lesions in the aorta of apoE-/- mice. We found that HT markedly lowered the levels of serum TG, TC, and LDL-C approximately by 17.4% (p=0.004), 15.2% (p=0.003), and 17.9% (p=0.009), respectively, as well as hepatic TG and TC by 15.0% (p<0.001) and 12.3% (p=0.003), respectively, while inducing a 26.9% (p=0.033) increase in serum HDL-C. Besides, HT improved hepatic steatosis and lipid deposition. Then, we discovered that HT could regulate the signal flow of AMPK/SREBP2 and increase the expression of ABCA1, apoAI, and SRBI. In addition, HT reduced the levels of serum CRP, TNF-α, IL-1β, and IL-6 approximately by 23.5% (p<0.001), 27.8% (p<0.001), 18.4% (p<0.001), and 19.1% (p<0.001), respectively, and induced a 1.4-fold increase in IL-10 level (p=0.014). Further, we found that HT might regulate cholesterol metabolism via decreasing phosphorylation of p38, followed by activation of AMPK and inactivation of NF-κB, which in turn triggered the blockade of SREBP2/PCSK9 and upregulation of LDLR, apoAI, and ABCA1, finally leading to a reduction of LDL-C and increase of HDL-C in the circulation. Conclusion. Our results provide the first evidence that HT displays antiatherosclerotic actions via mediating lipid metabolism-related pathways through regulating the activities of inflammatory signaling molecules.


2019 ◽  
Vol 17 ◽  
pp. 205873921985855
Author(s):  
Kaijian Hou ◽  
Wansheng Ke ◽  
Jianping Xiong

This study was designed to investigate the effect of metformin on the improvement of prostate cancer in diabetic rats. A total of 20 Sprague Dawley (SD) rats were equally divided into control and intervention groups. The intervention group received intragastric metformin 200 mg/kg, while the control group was given intragastric drinking water for 4 weeks. Tumor volumes were compared, all tumor specimens underwent routine pathological examination, immunohistochemical detection of E-cadherin and N-cadherin, and western blot assay. The tumor volume of control and intervention group was 462.15 ± 45.67 and 23.46 ± 5.32 mm3, respectively. Hematoxylin and eosin (HE) staining showed partial visible glandular structure with deepened nuclear staining in the intervention group. Immunohistochemistry showed high expression (6.5 ± 0.28 vs 3.8 ± 0.26, P < 0.05) of E-cadherin and low expression (3.4 ± 0.12 vs 7.8 ± 0.34, P < 0.05) of N-cadherin in the intervention group. Western blot assay showed higher expression of E-cadherin, while low N-cadherin in the intervention group. Metformin can effectively alleviate lesion extent of prostate cancer and mechanism may be related to upregulation of E-cadherin and downregulation of N-cadherin expression.


Author(s):  
Didem Yilmaz-Oral ◽  
Ecem Kaya-Sezginer ◽  
Dilan Askin ◽  
Yesim Hamurtekin ◽  
Serap Gur

Abstract Aim To investigate the possible beneficial effect of mirabegron [a selective β3-adrenoceptor (AR) agonist] treatment on erectile dysfunction (ED) in streptozotocin-induced diabetic rats. Methods Sprague-Dawley rats (n=20) were divided into two groups: control group and streptozotocin-induced diabetic group. In vivo erectile responses were evaluated after intracavernosal injection of mirabegron (0.4 mg/kg) in rats. The relaxation responses to electrical field stimulation (EFS, 10 Hz), sodium nitroprusside (SNP, 10 nM) and sildenafil (1 μM) of corpus cavernosum (CC) strips were examined after the incubation with mirabegron (10 μM). β3-ARs expression and localization were determined by Western blot and immunohistochemical analyses in CC tissue. Results In vivo erectile responses of diabetic rats [intracavernasal pressure (ICP) / mean arterial pressure, 0.17±0.01] were decreased, which were restored after administration of mirabegron (0.75±0.01, P<0.001). The basal ICP (7.1±0.6 mmHg) in diabetic rats was markedly increased after mirabegron (36.1 ±5.4 mmHg, P<0.01). Mirabegron caused markedly relaxation in diabetic rat CC after phenylephrine precontraction. The relaxation responses to EFS and sildenafil were reduced in diabetic CC, which were increased in the presence of mirabegron. Mirabegron enhanced SNP-induced relaxation response in both groups. The expression and immunoreactivity of β3-ARs localized to CC smooth muscle were observed in control and diabetic rats. Conclusions This is the first study to show that intracavernosal administration of mirabegron improved erectile function and neurogenic relaxation of CC in diabetic rats. These results may be supported by further studies using combinations of mirabegron and phosphodiesterase type 5 (PDE5) inhibitors for the treatment of diabetic ED, especially in patients who do not respond to PDE5 inhibitor therapy.


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