scholarly journals Streptozotocin-Induced Diabetes Models: Pathophysiological Mechanisms and Fetal Outcomes

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
D. C. Damasceno ◽  
A. O. Netto ◽  
I. L. Iessi ◽  
F. Q. Gallego ◽  
S. B. Corvino ◽  
...  

Glucose homeostasis is controlled by endocrine pancreatic cells, and any pancreatic disturbance can result in diabetes. Because 8% to 12% of diabetic pregnant women present with malformed fetuses, there is great interest in understanding the etiology, pathophysiological mechanisms, and treatment of gestational diabetes. Hyperglycemia enhances the production of reactive oxygen species, leading to oxidative stress, which is involved in diabetic teratogenesis. It has also been suggested that maternal diabetes alters embryonic gene expression, which might cause malformations. Due to ethical issues involving human studies that sometimes have invasive aspects and the multiplicity of uncontrolled variables that can alter the uterine environment during clinical studies, it is necessary to use animal models to better understand diabetic pathophysiology. This review aimed to gather information about pathophysiological mechanisms and fetal outcomes in streptozotocin-induced diabetic rats. To understand the pathophysiological mechanisms and factors involved in diabetes, the use of pancreatic regeneration studies is increasing in an attempt to understand the behavior of pancreatic beta cells. In addition, these studies suggest a new preventive concept as a treatment basis for diabetes, introducing therapeutic efforts to minimize or prevent diabetes-induced oxidative stress, DNA damage, and teratogenesis.

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Chonlathip Thipkaew ◽  
Jintanaporn Wattanathorn ◽  
Supaporn Muchimapura

In this study, quercetin-loaded zein-based nanofibers were developed using electrospinning technique. The therapeutic effect of these quercetin-loaded nanofibers on neuropathy in streptozotocin- (STZ-) induced diabetes in rats was assessed. Diabetic condition was induced in male Wistar rats by STZ, after which a crush injury of the right sciatic nerve was performed to induce mononeuropathy. Functional recovery was assessed using walking track analysis, measurements of foot withdrawal reflex, nerve conduction velocity, and morphological analysis. The oxidative stress status and the ratio of phosphorylated extracellular recognition kinase (pERK)/extracellular recognition kinase (ERK) expression in the nerve lesion were also assessed in order to elucidate the potential mechanisms involved. Results showed that quercetin-loaded zein-based nanofibers slightly enhanced functional recovery from neuropathy in STZ-diabetic rats. The potential mechanism might partially involve improvements in oxidative stress status and the ratio of pERK/ERK expression in the nerve lesion.


2008 ◽  
Vol 78 (45) ◽  
pp. 175-182 ◽  
Author(s):  
Masako Nakano ◽  
Natsumi Orimo ◽  
Nakako Katagiri ◽  
Masahito Tsubata ◽  
Jiro Takahashi ◽  
...  

In this study, the effect of dietary antioxidants, such as astaxanthin and Flavangenol®, and a combination of both, in counteracting oxidative stress in streptozotocin-induced diabetes was investigated. Streptozotocin-induced diabetic rats were divided into four groups: control, astaxanthin, Flavangenol, and combined astaxanthin and Flavangenol (mix group). Each group other than the control group was fed with an astaxanthin diet (0.1 g/kg), Flavangenol diet (2.0 g/kg), or an astaxanthin (0.1 g/kg)-Flavangenol (2.0 g/kg) mixture diet, respectively. After 12 weeks of feeding, the results showed that the lipid peroxide levels of plasma and lens and the plasma triglyceride (TG) level in the mix group were significantly decreased by 44%, 20%, and 20%, respectively, compared with the control group. In the mix group, lipid peroxidation was also significantly reduced by 70% in the liver and 20% in the kidney compared with the control group. Furthermore, the level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the mix group was significantly lower, 36%, than the control group. The α-tocopherol concentrations in the plasma, liver, and kidney in the astaxanthin and mix groups were significantly higher, 3-9 times, than in the control group. The degree of cataract formation in the Flavangenol and mix groups tended to be lower than the control group. These results indicate that the combination of astaxanthin with Flvangenol has an improved protective effect on oxidative stress associated with streptozotocin-induced diabetes than either agent used alone. Thus, this combination may be beneficial in preventing the progression of diabetic complications.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Horacio Osorio ◽  
Israel Coronel ◽  
Abraham Arellano ◽  
Ursino Pacheco ◽  
Rocío Bautista ◽  
...  

The hyperglycemia triggers several chronic diabetic complications mediated by increased oxidative stress that eventually causes diabetic nephropathy. The aim of this study was to examine if the sodium-glucose cotransporter (SGLT2) inhibition prevents the oxidative stress in the kidney of diabetic rats.Methods. The diabetic rat model was established by intraperitoneal injection of streptozotocin (50 mg/kg). The inhibition of SGLT2 was induced by daily subcutaneous administration of phlorizin (0.4 g/kg). Oxidative stress was assessed by catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities and by immunohistochemical analysis of 3-nitrotyrosine (3-NT).Results. Streptozotocin-induced diabetes caused hyperglycemia and lower body weight. The CAT activity decreased in cortex and medulla from diabetic rats; in contrast, the GPx activity increased. Furthermore the 3-NT staining of kidney from diabetic rats increased compared to control rats. The inhibition of SGLT2 decreased hyperglycemia. However, significant diuresis and glucosuria remain in diabetic rats. The phlorizin treatment restores the CAT and GPX activities and decreases 3-NT staining.Conclusion. The inhibition of SGLT2 by phlorizin prevents the hyperglycemia and oxidative stress in kidney of diabetic rats, suggesting a prooxidative mechanism related to SGLT2 activity.


2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Fábio Cangeri Di Naso ◽  
Rodrigo Noronha de Mello ◽  
Sílvia Bona ◽  
Alexandre Simões Dias ◽  
Marilene Porawski ◽  
...  

The present study was designed to evaluate the oxidative stress as well as the therapeutic effect ofAgaricus blazeiMuril (A. Blazei) in rats with streptozotocin-induced diabetes. We used 25 Wistar rats, and DM was induced by injecting streptozotocin (70 mg/Kg i.p.).Agaricus blazeiMuril was administered daily starting 40 days after disease onset.A. Blazeiwas tested as an aqueous extract for its phytochemical composition, and its antioxidant activity in vitro was also evaluated. Lipoperoxidation (LPO), and superoxide dismutase (SOD), catalase, and glutathione peroxidase activities were measured in the pulmonary tissue, as well as the presence of inducible nitric oxide synthase (iNOS), through immunohistochemistry. An anatomopathologic study was also performed. Phytochemical screening ofA. Blazeidetected the presence of alkaloids and saponins. The extract exhibited a significant antioxidant activity in the DPPH-scavenging and the hipoxanthine/xanthine oxidase assays. Pulmonary LPO increased in diabetic animals (0.43±0.09;P<.001) as compared to the control group (0.18±0.02), followed by a reduction in theA. Blazei-treated group (0.33±0.04;P<.05). iNOS was found increased in the lung in diabetic rats and reduced in theA. Blazei-treated group. The pulmonary tissue in diabetic rats showed oxidative alterations related to the streptozotocin treatment. TheA. Blazeitreatment effectively reduced the oxidative stress and contributed to tissue recovery.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Ghulam Mohammad ◽  
Mohammad Mairaj Siddiquei ◽  
Ahmed M. Abu El-Asrar

Retinal neuropathy is an early event in the development of diabetic retinopathy. One of the potential enzymes that are activated by oxidative stress in the diabetic retina is poly (ADP-ribose) polymerase (PARP). We investigated the effect of the PARP inhibitor 1,5-isoquinolinediol on the expression of the neurodegeneration mediators and markers in the retinas of diabetic rats. After two weeks of streptozotocin-induced diabetes, rats were treated with 1,5-isoquinolinediol (3 mg/kg/day). After 4 weeks of diabetes, the retinas were harvested and the levels of reactive oxygen species (ROS) were determined fluorometrically and the expressions of PARP, phosporylated-ERK1/2, BDNF, synaptophysin, glutamine synthetase (GS), and caspase-3 were determined by Western blot analysis. Retinal levels of ROS, PARP-1/2, phosphorylated ERK1/2, and cleaved caspase-3 were significantly increased, whereas the expressions of BDNF synaptophysin and GS were significantly decreased in the retinas of diabetic rats, compared to nondiabetic rats. Administration of 1,5-isoquinolinediol did not affect the metabolic status of the diabetic rats, but it significantly attenuated diabetes-induced upregulation of PARP, ROS, ERK1/2phosphorylation, and cleaved caspase-3 and downregulation of BDNF, synaptophysin, and GS. These findings suggest a beneficial effect of the PARP inhibitor in increasing neurotrophic support and ameliorating early retinal neuropathy induced by diabetes.


Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2872
Author(s):  
Chandra Sekhar Arigela ◽  
Giribabu Nelli ◽  
Siew Hua Gan ◽  
Kuttulebbai Nainamohamed Salam Sirajudeen ◽  
Kumarathevan Krishnan ◽  
...  

Honey has several pharmacological effects, including anti-diabetic activity. However, the effectiveness of bitter gourd honey (BGH) in the treatment of diabetes mellitus (DM) is unknown. The aim of this study was to determine the antioxidant, anti-inflammatory, and anti-apoptotic properties of BGH on the kidney and liver of a streptozotocin-induced diabetes rat model. Methods: A single dose (nicotinamide 110 mg/kg, streptozotocin (STZ) 55 mg/kg, intraperitoneal (i.p.)) was used to induce DM in male rats. For 28 days, normal or diabetic rats were administered 1 g/kg/day and 2 g/kg/day of BGH orally. After the treatment, blood, liver, and kidney samples were collected and analysed for biochemical, histological, and molecular parameters. In addition, liquid chromatography–mass spectrometry (LC-MS) was used to identify the major bioactive components in BGH. Results: The administration of BGH to diabetic rats resulted in significant reductions in alanine transaminase (ALT),aspartate aminotransferase (AST), creatinine, and urea levels. Diabetic rats treated with BGH showed lesser pathophysiological alterations in the liver and kidney as compared to non-treated control rats. BGH-treated diabetic rats exhibited reduced levels of oxidative stress (MDA levels), inflammatory (MYD88, NFKB, p-NFKB, IKKβ), and apoptotic (caspase-3) markers, as well as higher levels of antioxidant enzymes (SOD, CAT, and GPx) in the liver and kidney. BGH contains many bioactive compounds that may have antioxidative stress, anti-inflammatory, and anti-apoptotic effects. Conclusion: BGH protected the liver and kidney in diabetic rats by reducing oxidative stress, inflammation, and apoptosis-induced damage. As a result, BGH can be used as a potential therapy to ameliorate diabetic complications.


2008 ◽  
Vol 294 (5) ◽  
pp. H2305-H2312 ◽  
Author(s):  
Yu-Jung Chen ◽  
Jing Li ◽  
John Quilley

We confirmed that release of 20-hydroxyeicosatetraenoic acid (20-HETE) from the isolated perfused kidney of diabetic rats is greatly reduced compared with age-matched control rats. The present studies were undertaken to examine potential mechanisms for the deficit in renal 20-HETE in rats with streptozotocin-induced diabetes of 3–4 wk duration. A role for oxidative stress was excluded, inasmuch as treatment of diabetic rats with tempol, an SOD mimetic, for 4 wk did not affect the renal release of 20-HETE. Similarly, chronic inhibition of nitric oxide formation with nitro-l-arginine methyl ester or aldose reductase with zopolrestat failed to alter the release of 20-HETE from the diabetic rat kidney. Inasmuch as 20-HETE may be metabolized by cyclooxygenase (COX), the expression/activity of which is increased in diabetes, we included indomethacin in the perfusate of the isolated kidney to inhibit COX but found no effect on 20-HETE release. Diabetic rats were treated for 3 wk with fenofibrate to increase expression of cytochrome P-450 (CYP4A) in an attempt to find an intervention that would restore release of 20-HETE from the diabetic rat kidney. However, fenofibrate reduced 20-HETE release in diabetic and control rat kidneys but increased expression of CYP4A. Only insulin treatment of diabetic rats for 2 wk to reverse the hyperglycemia and maintain blood glucose levels at <200 mg/dl reversed the renal deficit in 20-HETE. We conclude that oxidative stress, increased aldose reductase activity, or increased COX activity does not contribute to the renal deficit of 20-HETE in diabetes, which may be directly related to insulin deficiency.


2018 ◽  
Vol 69 (1) ◽  
pp. 243 ◽  
Author(s):  
A. M.R. Afify ◽  
H. S. El-Beltagi ◽  
S. A. Fayed ◽  
A. E. El-Ansary

Diabetes mellitus type two (T2DM) is one of the most extensive diseases in the world. Herbal therapy remains a possible adjunct therapy to sustain better glycemic control and reduce complications arising from diabetes. In order to evaluate the curative impacts of olive leaf extract (OLE) on streptozotocin (STZ)-induced diabetic rats, twenty-four Wistar male adult rats were divided into four equal groups; control, diabetic control (45 mg/kg STZ), normal rats treated with OLE (17.8 mg/kg b.wt.), and diabetic rats treated with OLE (45 mg/kg STZ + 17.8 mg/kg b.wt.). The OLE extract was investigated for in vitro antioxidant activity using the DPPH• assay. The phenolic, tannin, and flavonoid contents were determined. The activity of GPX, SOD, and GSH in RBC lysate, CAT in plasma and MDA in serum were measured. The OLE prevented the decrease in GSH and kept MDA around the normal range in the treated diabetic rats. The current study suggests that OLE might be used safely to ameliorate T2DM and its accompanying oxidative stress.


2020 ◽  
pp. 53-60
Author(s):  
Sahar B. Ahmed ◽  
Ghada Khiralla ◽  
Shimaa Abdalla Harudy ◽  
Hesham Elhariry

Diabetic neuropathy is one of the complications of diabetes. This study investigated the possibility of reducing neuropathy of STZ-induced diabetic rats by Terminalia muelleri extract (TE) and comparing the effect of the extract with the therapeutic effect of pioglitazone (PG) drug. The experimental animals were divided into non-diabetic (normal control), STZ-induced diabetic (diabetic control), TE-treated non-diabetic (200 mg/kg b.wt) (TE-group) TE-treated diabetic (200 mg/kg b.wt) (TE-STZ-group), and pioglitazone-treated diabetic (1.58 mg /kg b.wt) (PG-STZ-group). All treatments were administered orally by oral gavage once daily throughout the 4 weeks of the treatment period. In this study: malonaldehyde, nitric oxide, reduced glutathione and glutathione disulfide were examined as oxidative stress marker in the brain tissue of the experimental rats. The results indicated high oxidative stress in STZ-diabetic groups and reduced oxidative stress of groups treated with TE. The results of norepinephrine, dopamine, gammaamino- butyric acid, brain-derived neurotrophic factor, and Casps-3 also demonstrated the possibility of using TE to attenuate the effects of neuropathy in experimental rats comparable to PG use. This indicated that the TE is promising alternative to chemical treatment with PG drug. This indicated that TE is promising alternative to chemical treatment with PG drug.


Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1423 ◽  
Author(s):  
Lech Sedlak ◽  
Weronika Wojnar ◽  
Maria Zych ◽  
Dorota Wyględowska-Promieńska ◽  
Ewa Mrukwa-Kominek ◽  
...  

Resveratrol is found in grapes, apples, blueberries, mulberries, peanuts, pistachios, plums and red wine. Resveratrol has been shown to possess antioxidative activity and a variety of preventive effects in models of many diseases. The aim of the study was to investigate if this substance may counteract the oxidative stress and polyol pathway in the lens of diabetic rats. The study was conducted on the rats with streptozotocin-induced type 1 diabetes. After the administration of resveratrol (10 and 20 mg/kg po for 4 weeks), the oxidative stress markers in the lens were evaluated: activity of superoxide dismutase, catalase and glutathione peroxidase, as well as levels of total and soluble protein, level of glutathione, vitamin C, calcium, sulfhydryl group, advanced oxidation protein products, malonyldialdehyde, Total Oxidant Status and Total Antioxidant Reactivity. The obtained results indicate that the administration of resveratrol to the diabetic rats shows antioxidative properties. It is not a result of antiglycaemic activity but resveratrol probably directly affects the antioxidative system. Resveratrol did not affect the polyol pathway in the lens of diabetic rats. Our results may indirectly indicate benefits of consumption of foods as well as dietary supplements containing resveratrol in diminishing oxidative stress in lenses of individuals suffering from diabetes mellitus.


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