scholarly journals Gold Nanoparticle-Bioconjugated Aminoguanidine Inhibits Glycation Reaction: An In Vivo Study in a Diabetic Animal Model

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Saheem Ahmad ◽  
Mohd. Sajid Khan ◽  
Sultan Alouffi ◽  
Saif Khan ◽  
Mahvish Khan ◽  
...  

Proteins undergo glycation resulting in the generation of advanced glycation end products (AGEs) that play a central role in the onset and advancement of diabetes-associated secondary complications. Aminoguanidine (AG) acts as an antiglycating agent by inhibiting AGE generation by blocking reactive carbonyl species (RCS) like, methylglyoxal (MGO). Previous studies on antiglycating behavior of AG gave promising results in the treatment of diabetes-associated microvascular complications, but it was discontinued as it was found to be toxic at high concentrations (>10 mmol/L). The current article aims at glycation inhibition by conjugating gold nanoparticles (Gnp) with less concentration of AG (0.5-1.0 mmol/L). The HPLC results showed that AG-Gnp fairly hampers the formation of glycation adducts. Moreover, the in vivo studies revealed AG-Gnp mediated inhibition in the production of total-AGEs and - N ε -(carboxymethyl)lysine (CML) in the diabetic rat model. This inhibition was found to be directly correlated with the antioxidant parameters, blood glucose, insulin, and glycosylated hemoglobin levels. Furthermore, the histopathology of AG-Gnp-treated rats showed good recovery in the damaged pancreatic tissue as compared to diabetic rats. We propose that this approach might increase the efficacy of AG at relatively low concentrations to avoid toxicity and might facilitate to overcome the hazardous actions of antiglycating drugs.

1977 ◽  
Vol 74 (2) ◽  
pp. 231-241 ◽  
Author(s):  
YVONNE MANGNALL ◽  
ANNE SMYTHE ◽  
D. N. SLATER ◽  
GILLIAN R. MILNER ◽  
R. D. G. MILNER ◽  
...  

Intraperitoneal transplantation of collagenase-digested, isogeneic, neonatal rat pancreatic tissue successfully reversed streptozotocin-induced diabetes in 77% of recipients. The low serum immunoreactive insulin, hyperglycaemia, glycosuria and weight loss, characteristic of the diabetic animal, were corrected and the reduced activities of hepatic glucokinase and pyruvate kinase, and the low glycogen concentration of the liver of diabetic rats were restored to normal. Forty-three per cent of the successfully transplanted rats became normoglycaemic within 1 month of transplantation whereas 57% took from 1 to 6 months to achieve normoglycaemia and displayed a mild glucose intolerance when subjected to a glucose load. The rats which had not become normoglycaemic 6 months after transplantation showed some amelioration of the diabetic state, as shown by increased serum immunoreactive insulin and hepatic glycogen concentration and a slow weight gain compared with diabetic controls.


1984 ◽  
Vol 247 (4) ◽  
pp. E526-E533
Author(s):  
A. S. Jennings

The effect of diabetes on 3,5,3'-triiodothyronine (T3) production was determined in the isolated perfused rat liver. Induction of diabetes with streptozotocin resulted in decreased serum thyroxine (T4) and T3 levels and a progressive decline in hepatic T3 production over 5 days. The decline in T3 production resulted from decreased conversion of T4 to T3, whereas T4 uptake was unchanged. Insulin administration restored serum T4 and T3, hepatic conversion of T4 to T3, and T3 production to normal levels. When serum T4 levels in diabetic rats were maintained by T4 administration, the conversion of T4 to T3 and T3 production returned to control levels. However, restoration of serum T4 levels in fasted rats failed to correct the decrease in hepatic T4 uptake or T3 production. Glucagon, at supraphysiological concentrations in vitro and in vivo, slightly decreased T4 uptake and T3 production without altering the conversion of T4 to T3. These data suggest that the fall in serum T4 levels observed in diabetic rats is important in mediating the decreased hepatic conversion of T4 to T3 and T3 production.


2021 ◽  
Author(s):  
Xiaofeng Zhang ◽  
Yujun Tang ◽  
Xiaoxian Guan ◽  
Xin Lu ◽  
Jiao Li ◽  
...  

Amomum tsao-ko Crevost et Lemarie (A. tsao-ko) is a well-known dietary spice and traditional Chinese medicine. This study aimed to identify the flavonoids in A. tsao-ko and evaluate its antioxidant...


1983 ◽  
Vol 245 (6) ◽  
pp. E560-E567 ◽  
Author(s):  
D. R. Bielefeld ◽  
C. S. Pace ◽  
B. R. Boshell

An alteration in calcium metabolism in cardiac muscle was observed in diabetic rats 3 mo after streptozotocin treatment. Depression of cardiac output and left ventricular pressure development were more sensitive to decreased extra-cellular calcium in hearts from diabetic than from control animals and occurred within the normal physiological range of freely ionized serum calcium. This decrease in calcium sensitivity was not present after 2 wk of diabetes. In vivo treatment with insulin for 1 mo completely reversed the effect. Addition of octanoate (0.3 mM) to the perfusate of isolated hearts completely reversed the defect, whereas epinephrine (25 nM) only partially reversed it. When the glucose concentration of the perfusate was decreased, the function of diabetic hearts declined and was further diminished at decreasing calcium levels. Hearts from normal rats were unaffected. These results suggest that there is a defect in calcium metabolism or flux in the chronic diabetic rat heart.


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.


Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582093942
Author(s):  
Muhammad Younus ◽  
Muhammad Mohtasheem ul Hasan ◽  
Khalil Ahmad ◽  
Ali Sharif ◽  
Hafiz Muhammad Asif ◽  
...  

In this study, we aimed to investigate the antidiabetic effects of Euphorbia nivulia (En), native to Cholistan Desert area of Bahawalpur, Pakistan. First, we performed high-performance liquid chromatography analysis and found that this plant contains ferulic acid, gallic acid, quercetin, benzoic acid, polyphenols, and flavonoids. Then, we performed in vitro and in vivo studies to assess its effects on diabetic Wistar rat model. The experiments were performed and compared with control drug glibenclamide. The 70% hydroalcoholic extract of En exhibited 97.8% in vitro α-glucosidase inhibitory effect at a dose of 1.0 mg/mL. We orally administered the extract of En and control drug to the streptozotocin (STZ)-induced diabetic rats and analyzed its antidiabetic effects. We found that the extract of En with a dose of 500 mg/kg/body weight exhibited significant effect to reduce blood glucose in STZ-induced rats as compared with the control group ( P < .001). Our histological data also showed that the extract significantly improved the histopathology of pancreas. Collectively, both in vitro and in vivo studies revealed that En possesses α-glucosidase inhibitory, antioxidant, and anti-hyperglycemic effect in STZ-induced diabetic rats.


2017 ◽  
Vol 30 (10) ◽  
Author(s):  
M. Saghazadeh‐Dezfuli ◽  
H. Fanaei ◽  
M. K. Gharib‐Naseri ◽  
S. Nasri ◽  
S. A. Mard

2013 ◽  
Vol 220 (3) ◽  
pp. 291-304 ◽  
Author(s):  
Mohamed Lotfy ◽  
Jaipaul Singh ◽  
Hameed Rashed ◽  
Saeed Tariq ◽  
Erika Zilahi ◽  
...  

Glucagon-like peptide 1 (GLP1) agonists are promising therapeutic agents in the treatment of diabetes mellitus. This study examines the mechanism of the protective effects of exenatide in experimental diabetes, employing four groups of ten rats each, in which two groups were streptozotocin-induced diabetic and two were control groups. One control and one diabetic group were treated with exenatide (1 μg/kg body weight (BW)) for 10 weeks. Blood plasma was taken for biochemical analyses while pancreatic tissue was taken for immunofluorescence and immunoelectron microscopy studies and real-time PCR to examine the expression of genes. The results show that exenatide improved BW gain and reduced blood glucose in diabetic rats compared with controls. Similarly, exenatide enhanced insulin release from the pancreatic fragments and improved liver and kidney functions and lipid profile in diabetic rats compared with controls. Exenatide not only induced significant increases in serum insulin level but also elevated the number of insulin-, GLP1- and exenatide-positive cells compared with untreated controls. Exenatide also elevated the number of catalase- and glutathione reductase-positive cells in diabetic rat pancreas compared with controls. Exenatide caused significant elevation in the expressions of pancreatic duodenal homeobox-1, heat shock protein-70, glutathione peroxidase, insulin receptor and GLP1 receptor genes in the pancreas of both control and diabetic rats compared with untreated animals. The results have demonstrated that exenatide can exert its beneficial and protective effects by elevating the levels of endogenous antioxidants and genes responsible for the survival, regeneration and proliferation of pancreatic β-cell.


2015 ◽  
Vol 6 (2) ◽  
pp. 113-118
Author(s):  
I. V. Prischepa ◽  
O. G. Prokushenkova ◽  
V. S. Nedzvetsky

Reactivation of glial cells, induced by metabolic disorders of glucose utilization and development of oxidative stress in retina under diabetes mellitus, is the key pathogenetic factor of diabetic retinopathy. Nanoparticles of C60 fullerene and some of their water-soluble derivates are known as one of the strongest antioxidants having neuroprotective effect in a number of pathologies and harmful influences. In the present study, for the first time, the effects of nanostructures of hydrated C60 fullerene (C60HyFn) on the expression and polypeptide composition of glial fibrillary acidic protein (GFAP) in retina of rats with streptozotocin (STZ)-induced diabetes have been evaluated. Using immunoblotting, 1.93-fold up-regulation of GFAP in diabetic rat retina as compared with control was shown, as a result of retinal glial cells reactivation induced by hyperglycemia. Increase in GFAP-immunolabeling associated with the reactive gliosis development in retina of diabetic rats was also confirmed by immuno-histochemical method. Consumption of C60HyFn solution (90 nM) as drinking water by diabetic rats for 12 weeks caused 1.51-fold decrease of GFAP level compared to untreated diabetic animals. In addition, C60HyFn caused statistically significant lowering of glycosylated hemoglobin concentration in blood serum of STZ-diabetic rats 1.58-fold. However, nanoparticles C60 did not affect neither insulin nor glucose levels in blood of diabetic rats. In conclusion, results obtained indicate that protective action of hydrated fullerene in the initial period of diabetic retinopathy of aged animals is realized through suppression of excessive activation of GFAP-positive retinal cells. 


2021 ◽  
Vol 9 (2) ◽  
pp. 189-199
Author(s):  
Md. Zia Uddin ◽  
◽  
Md. Sohel Rana ◽  
Subrata Chowdhury ◽  
Arkajyoti Paul ◽  
...  

The present research intended to explore the biological activities, namely acute toxicity test and hypoglycemic as well as in vitro anti-arthritic along with the antibacterial activity of crude methanol extracts with its different soluble fractions like petroleum ether (PESF), carbon tetrachloride (CTCSF), chloroform (CSF) and aqueous soluble fraction (AQSF) of Holigarna longifolia and Elatostema papillosum. Phytochemical screening was performed by established protocols. Acute toxicity and hypoglycemic effects were performed in experimental and alloxan-induced diabetic rats. In vitro anti-arthritic and antibacterial activity were conducted by protein denaturation inhibitory and disc diffusion methods. It was observed that no rats exhibit any lethality types, which reveal the safety of plant fractionates. It was also seen that both plants' fractionates showed significant (p < 0.01) activity on hyperglycemia compared to standard. Upon investigation, it was observed that crude methanol and its CS fraction of E. papillosum and only CS fraction of H. longifolia significantly (p < 0.05) inhibited denaturation of bovine serum albumin protein compared to standard diclofenac sodium. Moreover, it was observed that crude methanol extract and its CS fraction of E. papillosum showed significant inhibitory action on all Gram-positive bacteria's growth. In contrast, the PES fraction highlighted an inhibitory zone of 26.7 and 24.7 mm, respectively, towards B. subtilis and S. aureus. This study provides some support to explain the traditional uses of H. longifolia and E. papillosum.


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