scholarly journals Effects of enalapril and paricalcitol treatment on diabetic nephropathy and renal expressions of TNF-α, P53, Caspase-3 and Bcl-2 in STZ-induced diabetic rats

2019 ◽  
Author(s):  
Osama M. Ahmed ◽  
Tarek M. Ali ◽  
Mohamed A. Abdel Gaid ◽  
Ahmed A. Elberry
Keyword(s):  
Oxidative Stress ◽  
Wistar Rats ◽  
Antioxidant Defense ◽  
Caspase 3 ◽  
Enzyme Inhibitor ◽  
Elevated Serum ◽  
Antioxidant Defense System ◽  
Diabetic Rats ◽  
Defense System ◽  
Tnf Α

AbstractThis study aimed to assess the renopreventive effect of the angiotensin converting enzyme inhibitor (ACEI), enalapril, and/or vitamin D receptor (VDR) activator, paricalcitol, on streptozotocin (STZ) diabetes-induced nephropathy and to elucidate the mechanisms of action through investigation of the effects on renal oxidative stress, antioxidant defense system and expressions of TNF-α, P53, caspase-3, and Bcl-2. Diabetes mellitus was induced in fasting male Wistar rats by single intraperitoneal injection of STZ (45 mg /kg b.w.) dissolved in citrate buffer pH 4.5. Ten days after STZ injection, the diabetic rats were treated with enalapril (25 mg/l of drinking water) and/or paricalcitol (8 µg/kg b.w.per os) dissolved in 5% DMSO daily for 4 weeks. The obtained data revealed that the treatment of diabetic Wistar rats with enalapril and/or paricalcitol led to a significant decrease in the elevated serum urea, uric acid, creatinine and sodium, potassium levels; thereby reflecting improvement of the impaired kidney function. The deteriorated kidney lipid peroxidation, GSH content and GST and catalase activities in diabetic rats were significantly ameliorated as a result of treatment with enalapril and/or paricalcitol. The elevated fasting and post-prandial serum glucose levels and the lowered serum insulin and C-peptide levels were also improved. Moreover, the treatment of diabetic rats successfully prevented the diabetes-induced histopathological deleterious changes of kidney and islets of Langerhans of pancreas. In association, the immunohistochemically detected pro-inflammatory cytokine TNF-α and apoptotic mediators P53 and caspase-3 were remarkably decreased in kidney of diabetic rats as a result of treatment, while the expression of anti-apoptotic protein Bcl-2 was increased. Based on these findings, it can be concluded that enalapril and paricalcitol can prevent STZ diabetes-induced nephropathy though amelioration of the glycemic state and antioxidant defense system together with the suppression of oxidative stress, inflammation and apoptosis.

scholarly journals Antidiabetic Potency, Antioxidant Effects, and Mode of Actions of Citrus reticulata Fruit Peel Hydroethanolic Extract, Hesperidin, and Quercetin in Nicotinamide/Streptozotocin-Induced Wistar Diabetic Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
Alaa M. Ali ◽  
Mohamed Abdel Gabbar ◽  
Sanaa M. Abdel-Twab ◽  
Eman M. Fahmy ◽  
Hossam Ebaid ◽  
...  
Keyword(s):  
Antioxidant Defense ◽  
Elevated Serum ◽  
Antioxidant Defense System ◽  
Diabetic Rats ◽  
Oral Glucose ◽  
Citrus Reticulata ◽  
Defense System ◽  
Fruit Peel ◽  
Hydroethanolic Extract ◽  
Antioxidant Effects

This study is aimed at assessing the antihyperglycemic, antihyperlipidemic, and antioxidant effects of Citrus reticulata (C. reticulata) fruit peel hydroethanolic extract and two flavonoids, hesperidin and quercetin, in nicotinamide (NA)/streptozotocin- (STZ-) induced type 2 diabetic rats. In addition, GC-MS and HPLC-MS analyses of the extract were performed and the results indicated the presence of multiple flavonoids including hesperidin, quercetin, naringin, and polymethoxylated flavones (nobiletin and tangeretin). To achieve the aim of the study, diabetic rats with NA/STZ-induced T2DM were orally treated with C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin at a dose of 100 mg/kg b.w./day for four weeks. The treatments with C. reticulata fruit peel extract, hesperidin, and quercetin significantly ameliorated the impaired oral glucose tolerance; the elevated serum fructosamine level; the diminished serum insulin and C-peptide levels; the altered HOMA-IR, HOMA-IS, and HOMA-β cell function; the decreased liver glycogen content; the increased liver glucose-6-phosphatase and glycogen phosphorylase activities; the deleteriously affected serum lipid profile; the elevated serum AST and ALT activities; and the raised serum creatinine and urea levels in the diabetic rats. The treatments also produced remarkable improvement in the antioxidant defense system manifested by a decrease in the elevated liver lipid peroxidation and an increase in the lowered glutathione content and GPx, GST, and SOD activities. Furthermore, the three treatments enhanced the mRNA expression of GLUT-4 and the insulin receptor β-subunit, but only quercetin produced a significant increase in the expression of adiponectin in adipose tissue of diabetic rats. In conclusion, C. reticulata fruit peel hydroethanolic extract, hesperidin, and quercetin have potent antidiabetic effects which may be mediated through their insulinotropic effects and insulin-sensitizing actions. In addition, the alleviation of the antioxidant defense system by the extract, hesperidin, and naringin may have an important action to enhance the antidiabetic actions and to improve liver and kidney functions in NA/STZ-induced diabetic rats.

scholarly journals Oxidative stress/PERK/apoptotic pathways interaction contribute to tramadol neurotoxicity in rat cerebral and cerebellar cortex and thyme enhances the antioxidant defense system: histological, immunohistochemical and ultrastructural study

2018 ◽  
Vol 4 (6) ◽  
pp. 124 ◽  
Author(s):  
Nahla Reda Sarhan ◽  
Yasmeen Mohamed Taalab
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Cerebellar Cortex ◽  
Antioxidant Defense ◽  
Caspase 3 ◽  
Opioid Analgesic ◽  
Antioxidant Defense System ◽  
Ultrastructural Changes ◽  
Control Group ◽  
Defense System

<p class="abstract"><strong>Background:</strong> Tramadol is an opioid analgesic with several adverse reactions. Oxidative and endoplasmic reticulum (ER) stresses have been involved in the molecular mechanisms underlying tramadol neurotoxicity. Importantly, protein kinase RNA-like ER kinase (PERK) is a key ER-downstream pathway that mediates apoptosis. We aimed to determine the cellular stresses interaction that mediates PERK-induced apoptosis in tramadol-treated rats and to assess the effect of thyme in enhancing the antioxidant defense system in the face of such stresses.</p><p class="abstract"><strong>Methods:</strong> Forty male Sprague Dawley rats were randomized into 4 groups. Control group, thyme group received thyme extract (500 mg/kg/day) orally. Tramadol group received tramadol HCL (40 mg/Kg/day) dissolved in saline orally. Tramadol + Thyme group received tramadol and thyme extract. After 30 days, frontal motor and cerebellar cortex specimens were biochemically assessed for oxidative stress biomarkers and evaluated for histological, ultrastructural and immunohistochemical changes.  </p><p class="abstract"><strong>Results:</strong> Tramadol group showed a significant elevation in malondialdehyde level with a reduction in superoxide dismutase and catalase enzyme activities. Histologically and ultrastructurally, there were remarkable degenerative and apoptotic changes in the neurons and glial cells. In parallel, we detected a significant increase in integrated density for PERK immunostaining and number of caspase-3 positive cells/HPF compared to control. Tramadol + Thyme group showed improvement in oxidative stress parameters, histological and ultrastructural changes. Moreover, integrated density for PERK immunostaining and number of caspase-3 positive cells/HPF were significantly lower than Tramadol group.</p><p class="abstract"><strong>Conclusions:</strong> Oxidative and ER stress-mediated PERK/apoptosis axis corroborates to the tramadol-induced neurotoxicity. Therapeutic strategies enhancing antioxidant activity and/or blocking ROS-mediated ER stress pathway may resolve tramadol neurotoxicity.</p>

Skeletal muscle uncoupling-induced longevity in mice is linked to increased substrate metabolism and induction of the endogenous antioxidant defense system

2013 ◽  
Vol 304 (5) ◽  
pp. E495-E506 ◽  
Author(s):  
S. Keipert ◽  
M. Ost ◽  
A. Chadt ◽  
A. Voigt ◽  
V. Ayala ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Antioxidant Defense ◽  
Antioxidant Defense System ◽  
Mapk Signaling ◽  
Redox Signaling ◽  
Defense System ◽  
High Fat ◽  
Substrate Metabolism ◽  
Endogenous Antioxidant

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.

Impact of seasonally frozen soil on germinability and antioxidant enzyme activity of Picea asperata seeds

2009 ◽  
Vol 39 (4) ◽  
pp. 723-730 ◽  
Author(s):  
Jihong Qin ◽  
Qing Liu
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Defense ◽  
Germination Rate ◽  
Antioxidant Defense System ◽  
Antioxidant Enzyme Activity ◽  
Frozen Soil ◽  
Defense System ◽  
Frozen Ground ◽  
Subalpine Zone ◽  
Picea Asperata

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.

scholarly journals Curcumin Ameliorates Lead-Induced Hepatotoxicity by Suppressing Oxidative Stress and Inflammation, and Modulating Akt/GSK-3β Signaling Pathway

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 703 ◽  
Author(s):  
Ahlam Alhusaini ◽  
Laila Fadda ◽  
Iman H. Hasan ◽  
Enas Zakaria ◽  
Abeer M. Alenazi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caspase 3 ◽  
Tissue Injury ◽  
Elevated Serum ◽  
Antioxidant Defenses ◽  
Exact Role ◽  
Toxic Heavy Metal ◽  
Tnf Α ◽  
Gsk 3Β

Lead (Pb) is a toxic heavy metal pollutant with adverse effects on the liver and other body organs. Curcumin (CUR) is the principal curcuminoid of turmeric and possesses strong antioxidant and anti-inflammatory activities. This study explored the protective effect of CUR on Pb hepatotoxicity with an emphasis on oxidative stress, inflammation and Akt/GSK-3β signaling. Rats received lead acetate and CUR and/or ascorbic acid (AA) for seven days and samples were collected for analyses. Pb(II) induced liver injury manifested by elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), as well as histopathological alterations, including massive hepatocyte degeneration and increased collagen deposition. Lipid peroxidation, nitric oxide, TNF-α and DNA fragmentation were increased, whereas antioxidant defenses were diminished in the liver of Pb(II)-intoxicated rats. Pb(II) increased hepatic NF-κB and JNK phosphorylation and caspase-3 cleavage, whereas Akt and GSK-3β phosphorylation was decreased. CUR and/or AA ameliorated liver function, prevented tissue injury, and suppressed oxidative stress, DNA damage, NF-κB, JNK and caspase-3. In addition, CUR and/or AA activated Akt and inhibited GSK-3β in Pb(II)-induced rats. In conclusion, CUR prevents Pb(II) hepatotoxicity via attenuation of oxidative injury and inflammation, activation of Akt and inhibition of GSK-3β. However, further studies scrutinizing the exact role of Akt/GSK-3β signaling are recommended.

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