scholarly journals Beneficial Effects of Glucagon-Like Peptide-1 (GLP-1) in Diabetes-Induced Retinal Abnormalities: Involvement of Oxidative Stress

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 846
Author(s):  
Hugo Ramos ◽  
Patricia Bogdanov ◽  
Joel Sampedro ◽  
Jordi Huerta ◽  
Rafael Simó ◽  
...  

Background: Hyperglycemia-induced oxidative stress plays a key role in diabetic complications, including diabetic retinopathy. The main goal of this study was to assess whether the topical administration (eye drops) of glucagon-like peptide-1 (GLP-1) has any effect on oxidative stress in the retina. Methods: db/db mice were treated with eye drops of GLP-1 or vehicle for three weeks, with db/+ mice being used as control. Studies included the assessment by western blot of the antioxidant defense markers CuZnSOD, MnSOD, glutathione peroxidase and reductase; immunofluorescence measurements of DNA/RNA damage, nitro tyrosine and Ki67 and Babam2 proteins. Results: GLP-1 eye drops protected from oxidative stress by increasing the protein levels of glutathione reductase, glutathione peroxidase and CuZnSOD and MnSOD in diabetic retinas. This was associated with a significant reduction of DNA/RNA damage and the activation of proteins involved in DNA repair in the retina (Babam2) and Ki67 (a biomarker of cell proliferation). Conclusions: GLP-1 modulates the antioxidant defense system in the diabetic retina and has a neuroprotective action favoring DNA repair and neuron cells proliferation.

2022 ◽  
Vol 20 (4) ◽  
pp. 63-70
Author(s):  
O. V. Smirnova ◽  
V. V. Tsukanov ◽  
A. A. Sinyakov ◽  
O. L. Moskalenko ◽  
N. G. Elmanova ◽  
...  

Background. The problem of gastric cancer remains unresolved throughout the world, while chronic atrophic gastritis (CAG) increases the likelihood of its development by 15 times. In the Russian Federation, the incidence of gastric cancer (GC) is among the highest, with it prevailing among males. One of the leading mechanisms in molecular pathology of membranes is lipid peroxidation (LPO). The severity of oxidative membrane damage depends on concomitant diseases, contributing to emergence and progression of pathological processes and development of cancer. Currently, the problem of LPO is unsolved in biological systems.The aim of this study was to investigate the state of LPO and antioxidant defense system in CAG and GC. Materials and methods. The parameters were studied in 45 patients with CAG and 50 patients with GC. The control group included 50 practically healthy volunteers without gastrointestinal complaints, who did not have changes in the gastric mucosa according to the fibroesophagogastroduodenoscopy (FEGDS) findings.Results. In patients with CAG, an increase in malondialdehyde, superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase was found in the blood plasma compared with the control group. In patients with CAG, lipid peroxidation was activated, and the malondialdehyde level increased by 3.5 times relative to normal values. At the same time, the body fought against oxidative stress by increasing the activity of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase. All patients with GC showed pronounced oxidative stress in the blood plasma in the form of a 45-fold increase in malondialdehyde. The activity of the main antioxidant enzyme superoxide dismutase was reduced in GC. Catalase was activated, which indicated pronounced oxidative stress, significant damage to blood vessels, and massive cell death. Glutathione-related enzymes (glutathione S-transferase and glutathione peroxidase) and the antioxidant protein ceruloplasmin were activated, which also indicated significant oxidative stress and severe intoxication in patients with GC.Conclusion. Depending on the stage and type of cancer, an in-depth study of lipid peroxidation and factors of the antioxidant defense system can be used to correct therapy and prevent cancer and can serve as markers of progression and prognosis in gastric cancer. 


2016 ◽  
Vol 7 (1) ◽  
pp. 8-12
Author(s):  
T. V. Martyshuk

This article presents the results of research on the influence of oxidative stress on the intensity of the process of lipid peroxidation and the activity of the glutathione system of antioxidant defense in the organisms of rats. Intramuscular injection of 50% solution of tetrachloromethane at a dose of 0.25 ml per100 gof body weight to rats from the experimental group causes activation of the process of free radical lipid oxidation with excessive accumulation of intermediate anf final products of lipid peroxidation. The research results indicate that the development of oxidative stress leads to significant and probable acceleration of the formation and accumulation in the plasma of the rats, in all stages of the experiment, of lipid hydroperoxides and malonic dialdehyde. The highest level of hydroperoxides of lipids in the blood plasma of rats under oxidative stress was on the second day of the experiment, where it was 843 unE/ml, whereas in the control this index was 0.245 unE/ml. During the research into the content of malondialdehyde it was found that in the experimental group of animals it was 2.03 times higher than in the control group on the 5th day. On the 10th and 14th days of the experiment we observed a slight reduction in the levels of lipid hydroperoxides and malondialdehyde. The development of oxidative stress also leads to inhibition of the glutathione system of antioxidant defense in the rats’ organism. This shows the low activity of glutathione peroxidase and the low level of restored glutathione in the blood of the rats from the experimental group. On the 5th day of experiment the activity of glutathione peroxidase and restored glutathione level in the blood of the rats which were injected with carbon tetrachloride was at its lowest, compared with the control these indices decreased respectively by 53% and 51%. On the 10th and 14th days of the experiment the activity of glutathione peroxidase and restored glutathione level in the blood of the rats from the experimental group were slightly increased, but compared to the control they were still significantly lower. Significant disturbances were found in the oxidation-antioxidant balance of the animals under oxidative stress, which is characterized by the activation of the processes of free radical lipid oxidation with excessive accumulation of intermediate and final products and the inhibition of the antioxidant defense system.


2011 ◽  
Vol 35 (1) ◽  
pp. 81-87
Author(s):  
I. K. Latif

gainst damage initiated by a variety of endogenous and exogenous compounds. This study was conducted to evaluate the influence of Benzo[α]Pyrene (BαP) administration on the liver antioxidant defense system. Chicks were assigned into five equal groups, as control, tricaprylin group and three groups treated with BαP (1.5 μg, 150 μg or 15 mg/kg BW). Five birds were sacrificed at days 7, 14, 21 and 35 from each group. To assess the liver antioxidant defense system, glutathione (GSH) concentration, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) activities were employed. It was found that 15 mg of BαP level create significant increase (P<0.05) in the GSH level, GSH-Px, SOD and CAT activities (18.483, 9.88, 69.44 and 89.88 respectively) of broilers at day 7 post-instillation (p.i.) in compared with control (12.392, 6.51, 41.08 and 50.83). Nevertheless, significant decrease (P<0.05) in the GSH level, GSH-Px, SOD and CAT activities at 21 and 35 days. A key finding from this study is that exposure to BαP may induces oxidative stress on the liver and impair the antioxidant defense system in broilers.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Suvanjaa Sivalingam ◽  
Emil List Larsen ◽  
Daniel H. van Raalte ◽  
Marcel H. A. Muskiet ◽  
Mark M. Smits ◽  
...  

AbstractGlucagon-like peptide 1 receptor agonists have shown cardioprotective effects which have been suggested to be mediated through inhibition of oxidative stress. We investigated the effect of treatment with a glucagon-like peptide 1 receptor agonist (liraglutide) on oxidative stress measured as urinary nucleic acid oxidation in persons with type 2 diabetes. Post-hoc analysis of two independent, randomised, placebo-controlled and double-blinded clinical trials. In a cross-over study where persons with type 2 diabetes and microalbuminuria (LIRALBU, n = 32) received liraglutide (1.8 mg/day) or placebo for 12 weeks in random order, separated by 4 weeks of wash-out. In a parallel-grouped study where obese persons with type 2 diabetes (SAFEGUARD, n = 56) received liraglutide (1.8 mg/day), sitagliptin (100 mg/day) or placebo for 12 weeks. Endpoints were changes in the urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG)) and RNA oxidation [8-oxo-7,8-dihydroguanosine (8-oxoGuo)]. In LIRALBU, we observed no significant differences between treatment periods in urinary excretion of 8-oxodG [0.028 (standard error (SE): 0.17] nmol/mmol creatinine, p = 0.87) or of 8-oxoGuo [0.12 (0.12) nmol/mmol creatinine, p = 0.31]. In SAFEGUARD, excretion of 8-oxodG was not changed in the liraglutide group [2.8 (− 8.51; 15.49) %, p = 0.62] but a significant decline was demonstrated in the placebo group [12.6 (− 21.3; 3.1) %, p = 0.02], resulting in a relative increase in the liraglutide group compared to placebo (0.16 nmol/mmol creatinine, SE 0.07, p = 0.02). Treatment with sitagliptin compared to placebo demonstrated no significant difference (0.07 (0.07) nmol/mmol creatinine, p = 0.34). Nor were any significant differences for urinary excretion of 8-oxoGuo liraglutide vs placebo [0.09 (SE: 0.07) nmol/mmol creatinine, p = 0.19] or sitagliptin vs placebo [0.07 (SE: 0.07) nmol/mmol creatinine, p = 0.35] observed. This post-hoc analysis could not demonstrate a beneficial effect of 12 weeks of treatment with liraglutide or sitagliptin on oxidatively generated modifications of nucleic acid in persons with type 2 diabetes.


Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1118
Author(s):  
Jan Homolak ◽  
Ana Babic Perhoc ◽  
Ana Knezovic ◽  
Jelena Osmanovic Barilar ◽  
Melita Salkovic-Petrisic

The gastrointestinal system may be involved in the etiopathogenesis of the insulin-resistant brain state (IRBS) and Alzheimer’s disease (AD). Gastrointestinal hormone glucagon-like peptide-1 (GLP-1) is being explored as a potential therapy as activation of brain GLP-1 receptors (GLP-1R) exerts neuroprotection and controls peripheral metabolism. Intracerebroventricular administration of streptozotocin (STZ-icv) is used to model IRBS and GLP-1 dyshomeostasis seems to be involved in the development of neuropathological changes. The aim was to explore (i) gastrointestinal homeostasis in the STZ-icv model (ii) assess whether the brain GLP-1 is involved in the regulation of gastrointestinal redox homeostasis and (iii) analyze whether brain-gut GLP-1 axis is functional in the STZ-icv animals. Acute intracerebroventricular treatment with exendin-3(9-39)amide was used for pharmacological inhibition of brain GLP-1R in the control and STZ-icv rats, and oxidative stress was assessed in plasma, duodenum and ileum. Acute inhibition of brain GLP-1R increased plasma oxidative stress. TBARS were increased, and low molecular weight thiols (LMWT), protein sulfhydryls (SH), and superoxide dismutase (SOD) were decreased in the duodenum, but not in the ileum of the controls. In the STZ-icv, TBARS and CAT were increased, LMWT and SH were decreased at baseline, and no further increment of oxidative stress was observed upon central GLP-1R inhibition. The presented results indicate that (i) oxidative stress is increased in the duodenum of the STZ-icv rat model of AD, (ii) brain GLP-1R signaling is involved in systemic redox regulation, (iii) brain-gut GLP-1 axis regulates duodenal, but not ileal redox homeostasis, and iv) brain-gut GLP-1 axis is dysfunctional in the STZ-icv model.


2013 ◽  
Vol 304 (5) ◽  
pp. E495-E506 ◽  
Author(s):  
S. Keipert ◽  
M. Ost ◽  
A. Chadt ◽  
A. Voigt ◽  
V. Ayala ◽  
...  

Ectopic expression of uncoupling protein 1 (UCP1) in skeletal muscle (SM) mitochondria increases lifespan considerably in high-fat diet-fed UCP1 Tg mice compared with wild types (WT). To clarify the underlying mechanisms, we investigated substrate metabolism as well as oxidative stress damage and antioxidant defense in SM of low-fat- and high-fat-fed mice. Tg mice showed an increased protein expression of phosphorylated AMP-activated protein kinase, markers of lipid turnover (p-ACC, FAT/CD36), and an increased SM ex vivo fatty acid oxidation. Surprisingly, UCP1 Tg mice showed elevated lipid peroxidative protein modifications with no changes in glycoxidation or direct protein oxidation. This was paralleled by an induction of catalase and superoxide dismutase activity, an increased redox signaling (MAPK signaling pathway), and increased expression of stress-protective heat shock protein 25. We conclude that increased skeletal muscle mitochondrial uncoupling in vivo does not reduce the oxidative stress status in the muscle cell. Moreover, it increases lipid metabolism and reactive lipid-derived carbonyls. This stress induction in turn increases the endogenous antioxidant defense system and redox signaling. Altogether, our data argue for an adaptive role of reactive species as essential signaling molecules for health and longevity.


2009 ◽  
Vol 39 (4) ◽  
pp. 723-730 ◽  
Author(s):  
Jihong Qin ◽  
Qing Liu

In the subalpine zone of the Qinghai–Tibetan Plateau of China, Dragon spruce (Picea asperata Mast.) is commonly used for reforestation. The aim of the present work was to study the effects of seasonally frozen soil on the germination of P. asperata seeds and to investigate whether these effects were associated with resumption of the antioxidant defense system. The nonfrozen treatment resulted in near failure of germination (1%) and was associated with relatively high levels of hydrogen peroxide (H2O2) and low activities of superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxide (APX). Germination of P. asperata seeds at 10 cm under the seasonally frozen soil was higher than that at 5 cm by 26%; this higher germination rate was associated with the recovery of SOD, CAT, and APX activities. The levels of malondialdehyde (MDA) in seeds from seasonally frozen treatments were higher than those in the nonfrozen treatment, implying greater lipid peroxidation and that frozen seeds might have suffered from oxidative stress. The results indicate that seasonally frozen soil facilitated the germination of P. asperata seeds and that germination was closely related to the resumption of antioxidant enzymes activity. Overall, these findings suggest that the disappearance of seasonally frozen ground caused by global warming might result in failure of regeneration of P. asperata.


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