THE IMPACT OF METFORMIN AND ROSUVASTATIN ON THE MARKERS OF OXIDATIVE STRESS, GLYCEMIC CONTROL, AND LIPID PROFILE IN RATS WITH STREPTOZOTOCIN-NICOTINAMIDE-INDUCED DIABETES AFTER ACUTE INTRACEREBRAL HEMORRHAGE

Hyperproduction of highly active carbonyl compounds and reactive oxygen species initiates the development of oxidative stress in various pathological conditions and protein carbonylation is considered to be one of the key factors in the progression of diabetes mellitus and associated complications. This comparative research aimed to study the effect of metformin and rosuvastatin on the levels of biochemical markers of oxidative stress, glycemic control, and lipid profile in rats with type 2 diabetes mellitus (T2DM) complicated by a brain hemorrhage.T2DM was simulated with a single intraperitoneal injection of nicotinamide and streptozotocin (NA/STZ) to male Wistar rats (n=38). Intracerebral hemorrhage (ICH) was induced by microinjection of 1 μL of bacterial collagenase 0.2 IU/μL into the striatum. Animals were randomized into 5 groups: negative control, intact rats; positive control 1, NA/STZ; positive control 2, NA/STZ+ICH; metformin, 250 mg/kg +NA/STZ+ICH; rosuvastatin, 15 mg/kg+NA/STZ+ICH. Drug effects were assessed by the area under the glycemic curve (AUC), the content of glucose, glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), homocysteine (Hcy), advanced glycation end products (AGEs), and the markers of oxidative modification of proteins – aldehyde- and ketonephenylhydrazones (APH/KPH) in blood serum.It was found that brain hemorrhage in rats with T2DM can intensify the manifestations of oxidative modification of molecules and worsen glycemic control and lipid profile. Under these conditions, rosuvastatin improved lipid metabolism and reduced the levels of AGEs by 35.1% but did not affect glycemia and content of APH/KPH. Metformin reduced oxidative stress (AGEs by 35.4%, KPH by 21.2%) as well as improved both glycemic status and lipid profile (TG level by 20.2%, TG/HDL ratio by 31.9%). Both drugs did not produce any effect on Hcy level.Thus, metformin in conditions of T2DM complicated by acute ICH has advantages over rosuvastatin in relation to the markers of oxidative modification and glycemic control.

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Changes in biomarkers of endothelial function in the blood after intracerebral hemorrhage in rats with type 2 diabetes mellitus

Regulatory Mechanisms in Biosystems ◽

10.15421/0221101 ◽

2021 ◽

Vol 12 (4) ◽

pp. 733-739

Author(s):

А. E. Lievykh ◽

V. A. Tkachenko ◽

Y. V. Kharchenko ◽

A. I. Shevtsova ◽

G. A. Ushakova ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Endothelial Dysfunction ◽

Intracerebral Hemorrhage ◽

Lipid Profile ◽

Density Lipoprotein ◽

Oxidative Modification ◽

Oxidative Modification Of Proteins

Clinical evidence suggests that type 2 diabetes mellitus can increase the risk of intracerebral hemorrhage and provocation of neurodegeneration. This study was aimed at evaluating biomarkers of glycemic control, lipid profile, oxidative modification of proteins, as well as the functional state of endothelium in Wistar rats with type 2 diabetes mellitus complicated by intracerebral hemorrhage. Experimental type 2 diabetes mellitus was induced by intraperitoneal injection of streptozotocin (65 mg/kg) and nicotinamide (230 mg/kg). The intracerebral hemorrhage was induced by microinjection of sterile saline containing 0.2 IU bacterial collagenase into the striatum. Assessed biomarkers included the area under glycemic curve, glycated hemoglobin, total cholesterol, triglyceride, high-density lipoprotein, advanced glycation end products, markers of oxidative modification of proteins – aldehyde- and ketonephenylhydrazones, and markers of endothelial dysfunction – homocysteine, endothelin-1, von Willebrand factor and asymmetric dimethylarginine in blood serum. Both rats with type 2 diabetes mellitus and rats with intracerebral hemorrhage and diabetes had a significant elevated glycemic control as compared to intact animals. But combined pathology was additionally characterized by an impairment of lipid profile (increased triglyceride level and decreased as total cholesterol and high-density lipoprotein) resulting in a rise in the atherogenic index of plasma. A significant increase in the content of the markers of oxidative modification of proteins was observed in both experimental groups. But the rats with intracerebral hemorrhage and diabetes only had higher levels of advanced glycation end products in comparison with intact animals. The highest levels of endothelin-1, as a biomarker of endothelial dysfunction, were observed in animals with intracerebral hemorrhage and diabetes. Homocysteine and von Willebrand factor were elevated in rats with type 2 diabetes mellitus, while acute intracerebral hemorrhage did not potentiate the further growth in its levels. Such effect was not accompanied by a marked increase of asymmetric dimethylarginine level in blood serum, although there was a clear trend. In conclusion, the development of intracerebral hemorrhage in rats with type 2 diabetes mellitus can intensify the manifestations of oxidative stress, worsen lipid profile, and aggravate endothelial dysfunction. In this case, the pathological process may have the character of a “vicious circle”.

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Assessment of biomarkers of inflammation and premature atherosclerosis in adolescents with type-1 diabetes mellitus

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2018-0192 ◽

2019 ◽

Vol 32 (2) ◽

pp. 109-113 ◽

Cited By ~ 6

Author(s):

Ghufran Babar ◽

Mark Clements ◽

Hongying Dai ◽

Geetha Raghuveer

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Glycemic Control ◽

Type 1 Diabetes Mellitus ◽

Pearson Correlation ◽

Premature Coronary Artery Disease ◽

The Impact ◽

Early Atherosclerosis

Abstract Background Type-1 diabetes mellitus (T1DM) causes endothelial dysfunction and early atherosclerosis, which can result in premature coronary artery disease. The aim of this study was to determine the impact of glycemic control, vascular oxidative stress and inflammation on vascular health in adolescents with T1DM. Methods This was a cross-sectional study in adolescents with age- and sex-matched T1DM who were ≥12 years and were at least 2 years post-diagnosis. Recruitment was balanced to include individuals with hemoglobin A1c (HbA1c) ≤8.5% (n=27) or with HbA1c ≥9.5% (n=25). Biomarkers of inflammation were measured in the blood including C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), E-selectin, fibrinogen and tumor necrosis factor-α (TNF-α). Carotid intima media thickness (cIMT) and peripheral arterial tonometry (PAT) were assessed. Results Plasma E-selectin level was significantly different between the two groups with higher levels in the group with HbA1c ≥9.5% (65.0±27.7 ng/mL vs. 48.8±21.5 ng/mL, p=0.02). Though cIMT and PAT were not significantly different between the groups, Pearson correlation showed a significant direct relationship between rising HbA1c and mean right cIMT (p=0.02; r=0.37), PAT (p=0.03, r=0.31) and fibrinogen (p=0.03, r=0.03). Conclusions Elevated E-selectin level is an early marker of oxidative stress in T1DM patients with an elevated HbA1c level. Suboptimal glycemic control as evidenced by a rising HbA1c causes early atherosclerosis.

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Effect of Cichorium intybus seeds supplementation on the markers of glycemic control, oxidative stress, inflammation, and lipid profile in type 2 diabetes mellitus: A randomized, double‐blind placebo study

Phytotherapy Research ◽

10.1002/ptr.6624 ◽

2020 ◽

Vol 34 (7) ◽

pp. 1609-1618 ◽

Cited By ~ 2

Author(s):

Kailash Chandra ◽

Vineet Jain ◽

Azhar Jabin ◽

Shridhar Dwivedi ◽

Santosh Joshi ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glycemic Control ◽

Lipid Profile ◽

Cichorium Intybus ◽

Double Blind ◽

Double Blind Placebo

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The impact of perindopril and metformin on the markers of endothelial dysfunction in rats with acute intracerebral hemorrhage and type 2 diabetes mellitus

Medicni perspektivi (Medical perspectives) ◽

10.26641/2307-0404.2021.4.248055 ◽

2021 ◽

Vol 26 (4) ◽

pp. 15-22

Author(s):

V.I. Zhyliuk ◽

A.E. Lievykh ◽

A.I. Shevtsova ◽

V.A. Tkachenko ◽

Yu.V. Kharchenko

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Endothelial Dysfunction ◽

Intracerebral Hemorrhage ◽

Positive Control ◽

Brain Hemorrhage ◽

Acute Intracerebral Hemorrhage ◽

The Impact

This comparative research is aimed to study the effect of perindopril and metformin on the levels of biochemical markers of endothelial dysfunction in rats with type 2 diabetes mellitus (T2DM) complicated by a brain hemorrhage. The study was carried out on 30 white male Wistar rats. T2DM was simulated by a single intraperitoneal injection of nicotinamide and streptozotocin (NA/STZ). Intracerebral hemorrhage (ICH) was induced by microinjection of 1 μL of bacterial collagenase 0.2 IU/μL into the striatum on the 60th day of the experiment. Animals were randomized into 5 groups: A – negative control (intact, n=6); B – positive control 1 (NA/STZ, n=6); C – positive control 2 (NA/STZ+ICH, n=6); D – perindopril (“Prestarium”, 2 mg/kg+NA/STZ+ICH, n=6); E – metformin (“Siofor”, 250 mg/kg+NA/STZ+ICH, n=6). The studied drugs were administered intragastrically for 20 days, starting from the 50th day after the induction of T2DM. Endothelial function was assessed by the content of homocysteine (Hcy), advanced glycation end products (AGEs), endothelin-1 (ET-1), and von Willebrand factor (vWF) in blood serum. It was found that long-term separate T2DM is accompanied by hyperhomocysteinemia, as well as an increase in AGEs, ET-1, and vWF levels, indicating dysregulation of the hemostasis system and vascular tone. It should be noted that brain hemorrhage in T2DM can enhance these manifestations, although the obtained differences were characterized only by a persistent trend. At the same time, the effect of perindopril was limited only by a significant decrease in AGEs levels by 31.2% (p<0.05). In turn, the action of metformin was characterized by a positive glycemic control, as well as an effect on the state of the vascular endothelium, namely, a significant decrease in AGEs, ET-1 and vWF levels by 37.6% (p<0.05); 5.5% (p<0.05) and 9.5% (p<0.05), respectively. It was also found that the endotheliotropic properties of the studied drugs were not associated with an effect on homocysteine levels. Thus, metformin in conditions of diabetes mellitus complicated by acute intracerebral hemorrhage has advantages over perindopril in relation to endothelial dysfunction.

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MDA levels in the pancreas, testes, liver, and plasma of diabetic rats: The effect of snakehead (Channa striata) extract

Nusantara Bioscience ◽

10.13057/nusbiosci/n120109 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

NURLITA ABDULGANI ◽

DEWI HIDAYATI ◽

RESSY ADINOVITASARY ◽

VARAH OLIVIATIE ◽

AYU DIAH SEKARTAJI

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Low Dose ◽

Positive Control ◽

Negative Control ◽

Diabetic Rats ◽

High Dose ◽

Channa Striata ◽

Negative Controls ◽

Biomarkers Of Oxidative Stress

Abstract. Abdulgani N, Hidayati D, Adinovitasary R, Oliviatie V, Sekartaji AD. 2020. MDA levels in the pancreas, testes, liver, and plasma of diabetic rats: The effect of snakehead (Channa striata) extract. Nusantara Bioscience 12: 50-54. There are several biomarkers of oxidative stress in diabetes mellitus; one of those biomarkers is Malondialdehyde (MDA). Increasing oxidative stress will cause increased tissue damage. This study was conducted to determine the effect of snakehead extract (SHE) on MDA level of pancreas, testes, liver, and plasma of alloxan-induced diabetic rats. There were 5 groups of treatments: non-diabetic rats/negative control (C-), diabetic rats/positive control (C+), and 3 SHE level of administration: 1 mL/day (low dose/LD), 1.6 mL/day (middle dose/MD) and 2.1 mL/day (high dose/HD). Alloxan-induced diabetic rats were administered with SHE extract orally every day for two weeks. The results showed that MDA levels in the testes, liver, pancreas, and plasma of diabetic rats administered with SHE and non-diabetic rats/negative controls (C-) were significantly lower (p <0.05) compared to MDA levels in the testes, liver, pancreas, and plasma of diabetic rats without SHE administration (positive control/ C +). The highest dose of SHE treatment (2.1 mL/day) results in decreasing MDA levels were not significantly different (p> 0.05) with the group of non-diabetic rats / negative controls (C-). The conclusion of this study was increasing SHE administration up to 2.1 mL/day result in reducing more of MDA levels in plasma, pancreas, liver, and testes of diabetic rats.

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The Effect Of Sea Cucumber Powder And Hyperbaric Oxygen Therapy On The Expression Of Tumor Necrosis Factor Alfa In Rats With Diabetes Mellitus Induced By Porphyromonas gingivalis

DENTA ◽

10.30649/denta.v10i1.40 ◽

2016 ◽

Vol 10 (1) ◽

pp. 79

Author(s):

Caroline Prajnaparamitha Anggraini ◽

Kristanti Parisihni ◽

Widyastuti W

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Hyperbaric Oxygen ◽

Hyperbaric Oxygen Therapy ◽

Sea Cucumber ◽

Oxygen Therapy ◽

Positive Control ◽

Negative Control ◽

Tnf Α ◽

Immunohistochemistry Stain

Background: Periodontitis have a bidirectional relationship with diabetes mellitus, both can increase oxidative stress that trigger an increase of pro-inflammatory cytokines, such as TNF-α. Sea cucumbers have anti-inflammatory component that act to inhibit the release of inflammatory mediators. Hyperbaric oxygen therapy reduce oxidative stress. Purpose: The aim of this study is to investigate the effect of the sea cucumber powder and hyperbaric oxygen therapy on the expression of TNF-α in rats with diabetes mellitus induced by P.gingivalis bacteria. Materials and Methods: The study was an experimental laboratories research with factorial design. Twenty wistar rats were divided into 5 groups. K0 negative control, K1 positive control. K1-K4 groups were induced with streptozotocin for diabetes condition and P.gingivalis bacteria for periodontitis condition. K2 group was treated with sea cucumber 3% for 7 days, K3 with OHB 2.4 ATA 3 x 30’ interval 5’ for 7 days, and K4 group was treated with combination of sea cucumber and OHB. At the 51st day all rats were sacrified, then the expression of TNF-α on periodontal macrophages were examined by immunohistochemistry stain. Data were analized by Kruskal Wallis followed by Mann-whitney. Result: Expression of TNF-α were increased in K1 (11.50±1.291) compare K0 (p<0.05). Sea cucumber treatment, OHB, and combination treatment decreased expression of TNF-α significantly in amount of 2.50±0.577 (K2), 8.25±2.217 (K3), 3.00±0.816 (K4). Conclusion: Sea cucumber powder and OHB therapy affected the expression of TNF-α in rats with diabetes mellitus induced by P. gingivalis bacteria.

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Glycemic control, oxidative stress, and lipid profile in children with type 1 diabetes mellitus

Archives of Medical Research ◽

10.1016/j.arcmed.2003.10.002 ◽

2004 ◽

Vol 35 (2) ◽

pp. 134-140 ◽

Cited By ~ 40

Author(s):

Füsun Erciyas ◽

Fatma Taneli ◽

Banu Arslan ◽

Yasemin Uslu

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Glycemic Control ◽

Type 1 Diabetes Mellitus ◽

Lipid Profile

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UJI AKTIVITAS HEPATOPROTEKTOR KOMBINASI EKSTRAK ETANOL DAUN PANDAN WANGI (Pandanus amaryllifolius roxb) DAN KAYU MANIS (Cinnamomum burmanii) TERHADAP KADAR MDA YANG DIINDUKSI PARASETAMOL

Jurnal Kesehatan Kusuma Husada ◽

10.34035/jk.v12i1.580 ◽

2020 ◽

pp. 68-73

Author(s):

Yuni Asri Mulatsih Agami ◽

Eka Wisnu Kusuma

Keyword(s):

Oxidative Stress ◽

Ethanol Extract ◽

Optimal Dose ◽

Experimental Methods ◽

Positive Control ◽

Negative Control ◽

Male Rats ◽

Negative Group ◽

Ic50 Value ◽

Dose Combination

Kasus penyakit hati semakin meningkat seiring penggunaan senyawa hepatotoksin salah satunya karena penggunaan parasetamol dengan dosis berlebih. Hal tersebut dapat meningkatkan produksi radikal bebas sehingga memicu terjadinya stress oksidatif yang dapat menimbulkan kerusakan jaringan yang ditandai dengan peningkatan kadar Malondialdehyde (MDA). Stress oksidatif dapat diatasi dengan antioksidan dari berbagai tanaman. Kulit kayu manis memiliki aktivitas antioksidan dengan nilai IC50 53ppm dan daun pandan wangi 39,7% Penelitian ini bertujuan untuk mengetahui aktivitas kombinasi ekstrak etanol daun pandan wangi dan kayu manis dalam menurunkan kadar MDA. tikus yang diinduksi parasetamol. Penelitian menggunakan metode eksperimental, dilakukan selama 9 hari dengan 30 ekor tikus jantan dibagi menjadi 6 Kelompok, yaitu: Normal diberi aquadest, Kontrol Positif diberi silimarin 100 mg/kgBB, Kontrol Negatif diberi CMC-Na 0,05%, serta 3 kelompok lainnya diberi kombinasi ekstrak daun pandan wangi:kayu manis berturut-turut dosis I (25:75), dosis II (50:50), dosis III (75:25). Semua kelompok diinduksi parasetamol 2,5 g/kgBB pada hari ke-7 setelah 30 menit perlakuan, kecuali kelompok normal. Pada hari ke 9 dilakukan pengukuran kadar MDA dengan metode TBARs menggunakan spektrofotometri. Pemberian kombinasi ekstrak etanol daun pandan wangi dan kayu manis dapat menurunkan kadar MDA dengan kombinasi dosis yang paling optimal adalah 75:25 berdasarkan statistik dengan nilai signifikan 0,000<0,05 dibandingkan dengan kelompok negatif. Cases of liver disease have increased with the use of hepatotoxin compounds, one of which is due to the use of paracetamol with excessive doses. This can increase the production of free radicals so that it triggers oxidative stress which can cause tissue damage which is characterized by increased levels of Malondialdehyde (MDA). Oxidative stress can be overcome with antioxidants from various plants. Cinnamomum burmanii has antioxidant activity with IC50 value of 53ppm and Pandanus amarrylifolius 39.7%. This study aims to determine the combined activity of ethanol extract of Pandanus amarrylifolius and Cinnamomum burmanii in reducing MDA levels. Paracetamol-induced rats. Research using experimental methods, conducted for 9 days with 30 male rats divided into 6 groups, namely: Normal given aquadest, Positive Control were given silimarin 100 mg / kgBB, Negative Control was given CMC-Na 0.05%, and 3 other groups were given a combination of Pandanus amarrylifolius extract: Cinnamomum burmanii dose I (25:75), dose II (50:50), dose III (75:25). All groups induced paracetamol 2.5 g / kgBB on the 7th day after 30 minutes of treatment, except the normal group. On the 9th day MDA levels were measured using the TBARs method using spectrophotometry. Giving a combination of Pandanus amarrylifolius and Cinnamomum burmanii ethanol extract can reduce MDA levels with the most optimal dose combination is 75:25 based on statistics with a significant value of 0,000<0.05 compared with the negative group.

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The Antioxidant Effect of Curcumin and Rutin on Oxidative Stress Biomarkers in Experimentally Induced Periodontitis in Hyperglycemic Wistar Rats

Molecules ◽

10.3390/molecules26051332 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1332

Author(s):

Gilda M. Iova ◽

Horia Calniceanu ◽

Adelina Popa ◽

Camelia A. Szuhanek ◽

Olivia Marcu ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Diabetic Rats ◽

Gingival Tissue ◽

Control Group ◽

Albino Rats ◽

Oxidative Stress Biomarkers ◽

Significant Difference ◽

The Impact ◽

Experimentally Induced

Background: There is a growing interest in the correlation between antioxidants and periodontal disease. In this study, we aimed to investigate the effect of oxidative stress and the impact of two antioxidants, curcumin and rutin, respectively, in the etiopathology of experimentally induced periodontitis in diabetic rats. Methods: Fifty Wistar albino rats were randomly divided into five groups and were induced with diabetes mellitus and periodontitis: (1) (CONTROL)—control group, (2) (DPP)—experimentally induced diabetes mellitus and periodontitis, (3) (DPC)—experimentally induced diabetes mellitus and periodontitis treated with curcumin (C), (4) (DPR)—experimentally induced diabetes mellitus and periodontitis treated with rutin (R) and (5) (DPCR)—experimentally induced diabetes mellitus and periodontitis treated with C and R. We evaluated malondialdehyde (MDA) as a biomarker of oxidative stress and reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG and catalase (CAT) as biomarkers of the antioxidant capacity in blood harvested from the animals we tested. The MDA levels and CAT activities were also evaluated in the gingival tissue. Results: The control group effect was statistically significantly different from any other groups, regardless of whether or not the treatment was applied. There was also a significant difference between the untreated group and the three treatment groups for variables MDA, GSH, GSSG, GSH/GSSG and CAT. There was no significant difference in the mean effect for the MDA, GSH, GSSG, GSH/GSSG and CAT variables in the treated groups of rats with curcumin, rutin and the combination of curcumin and rutin. Conclusions: The oral administration of curcumin and rutin, single or combined, could reduce the oxidative stress and enhance the antioxidant status in hyperglycemic periodontitis rats.

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