Role of nitric oxide and oxidative stress in pathophysiology of liver injury in streptozotocin-induced type 1 diabetic rats

Abstract Objectives The current study evaluates the protective role of aqueous extract of Sterculia tragacantha leaf (AESTL) on pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67 and GLP-1R) and oxidative stress parameters in streptozotocin-induced diabetic rats. Methods Diabetes mellitus was induced into the experimental Wistar animals via intraperitoneal (IP) injection of streptozotocin (35 mg/kg body weight) and 5% glucose water was given to the rats for 24 h after induction. The animals were categorized into five groups of 10 rats each as follows normal control, diabetic control, diabetic rats administered AESTL (150 and 300 mg/kg body weight) and diabetic rats administered metformin (200 mg/kg) orally for two weeks. Thereafter, the animals were euthanized, blood sample collected, pancreas harvested and some pancreatic gene expressions (such as insulin, PCNA, PDX-1, KI-67, and GLP-1R)s as well as oxidative stress parameters were analyzed. Results The results revealed that AESTL significantly (p<0.05) reduced fasting blood glucose level, food and water intake, and lipid peroxidation in diabetic rats. Diabetic rats administered different doses of AESTL showed a substantial upsurge in body weight, antioxidant enzyme activities, and pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67, and GLP-1R). Conclusions It can therefore be concluded that AESTL has the ability to protect the pancreas during diabetes mellitus conditions.

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The role of oxidative/nitrosative stress in pathogenesis of paracetamol-induced toxic hepatitis

Medicinski pregled ◽

10.2298/mpns1012827r ◽

2010 ◽

Vol 63 (11-12) ◽

pp. 827-832 ◽

Cited By ~ 7

Author(s):

Tatjana Radosavljevic ◽

Dusan Mladenovic ◽

Danijela Vucevic ◽

Rada Jesic-Vukicevic

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Reactive Oxygen Species ◽

Liver Injury ◽

Kupffer Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Severe Liver ◽

Hepatocellular Necrosis

Introduction. Paracetamol is an effective analgesic/antipyretic drug when used at therapeutic doses. However, the overdose of paracetamol can cause severe liver injury and liver necrosis. The mechanism of paracetamol-induced liver injury is still not completely understood. Reactive metabolite formation, depletion of glutathione and alkylation of proteins are the triggers of inhibition of mitochondrial respiration, adenosine triphosphate depletion and mitochondrial oxidant stress leading to hepatocellular necrosis. Role of oxidative stress in paracetamol-induced liver injury. The importance of oxidative stress in paracetamol hepatotoxicity is controversial. Paracetamol induced liver injury cause the formation of reactive oxygen species. The potent sources of reactive oxygen are mitochondria, neutrophils, Kupffer cells and the enzyme xatnine oxidase. Free radicals lead to lipid peroxidation, enzymatic inactivation and protein oxidation. Role of mitochondria in paracetamol-induced oxidative stress. The production of mitochondrial reactive oxygen species is increased, and the glutathione content is decreased in paracetamol overdose. Oxidative stress in mitochondria leads to mito?chondrial dysfunction with adenosine triphosphate depletion, increase mitochondrial permeability transition, deoxyribonu?cleic acid fragmentation which contribute to the development of hepatocellular necrosis in the liver after paracetamol overdose. Role of Kupffer cells in paracetamol-induced liver injury. Paracetamol activates Kupffer cells, which then release numerous cytokines and signalling molecules, including nitric oxide and superoxide. Kupffer cells are important in peroxynitrite formation. On the other hand, the activated Kupffer cells release anti-inflammatory cytokines. Role of neutrophils in paracetamol-induced liver injury. Paracetamol-induced liver injury leads to the accumulation of neutrophils, which release lysosomal enzymes and generate superoxide anion radicals through the enzyme nicotinamide adenine dinucleotide phosphate oxidase. Hydrogen peroxide, which is influenced by the neutrophil-derived enzyme myeloperoxidase, generates hypochlorus acid as a potent oxidant. Role of peroxynitrite in paracetamol-induced oxidative stress. Superoxide can react with nitric oxide to form peroxynitrite, as a potent oxidant. Nitrotyrosine is formed by the reaction of tyrosine with peroxynitrite in paracetamol hepatotoxicity. Conclusion. Overdose of paracetamol may produce severe liver injury with hepatocellular necrosis. The most important mechanisms of cell injury are metabolic activation of paracetamol, glutathione depletion, alkylation of proteins, especially mitochondrial proteins, and formation of reactive oxygen/nitrogen species.

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Effects of sodium-glucose cotransporter 2 selective inhibitor ipragliflozin on hyperglycaemia, oxidative stress, inflammation and liver injury in streptozotocin-induced type 1 diabetic rats

Journal of Pharmacy and Pharmacology ◽

10.1111/jphp.12223 ◽

2014 ◽

Vol 66 (7) ◽

pp. 975-987 ◽

Cited By ~ 50

Author(s):

Atsuo Tahara ◽

Eiji Kurosaki ◽

Masanori Yokono ◽

Daisuke Yamajuku ◽

Rumi Kihara ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Diabetic Rats ◽

Selective Inhibitor ◽

Sodium Glucose Cotransporter

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Beneficial Effect of Aqueous Garlic Extract on Inflammation and Oxidative Stress Status in the Kidneys of Type 1 Diabetic Rats

Indian Journal of Clinical Biochemistry ◽

10.1007/s12291-016-0621-6 ◽

2016 ◽

Vol 32 (3) ◽

pp. 329-336 ◽

Cited By ~ 12

Author(s):

Abolfazl Nasiri ◽

Nasrin Ziamajidi ◽

Roghayeh Abbasalipourkabir ◽

Mohammad Taghi Goodarzi ◽

Massoud Saidijam ◽

...

Keyword(s):

Oxidative Stress ◽

Beneficial Effect ◽

Diabetic Rats ◽

Garlic Extract ◽

Oxidative Stress Status ◽

And Oxidative Stress

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Edaravone for the treatment of acute cerebral infarction: role of endothelium-derived nitric oxide and oxidative stress

Expert Opinion on Pharmacotherapy ◽

10.1517/14656560802636888 ◽

2009 ◽

Vol 10 (2) ◽

pp. 323-331 ◽

Cited By ~ 28

Author(s):

Yukihito Higashi

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Cerebral Infarction ◽

Acute Cerebral Infarction ◽

And Oxidative Stress

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The Role of MicroRNAs in Diabetes-Related Oxidative Stress

International Journal of Molecular Sciences ◽

10.3390/ijms20215423 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5423 ◽

Cited By ~ 3

Author(s):

Mirza Muhammad Fahd Qadir ◽

Dagmar Klein ◽

Silvia Álvarez-Cubela ◽

Juan Domínguez-Bendala ◽

Ricardo Luis Pastori

Keyword(s):

Oxidative Stress ◽

Target Gene ◽

Cellular Stress ◽

Cellular Damage ◽

Oxygen Species ◽

Non Coding Rnas ◽

And Oxidative Stress

Cellular stress, combined with dysfunctional, inadequate mitochondrial phosphorylation, produces an excessive amount of reactive oxygen species (ROS) and an increased level of ROS in cells, which leads to oxidation and subsequent cellular damage. Because of its cell damaging action, an association between anomalous ROS production and disease such as Type 1 (T1D) and Type 2 (T2D) diabetes, as well as their complications, has been well established. However, there is a lack of understanding about genome-driven responses to ROS-mediated cellular stress. Over the last decade, multiple studies have suggested a link between oxidative stress and microRNAs (miRNAs). The miRNAs are small non-coding RNAs that mostly suppress expression of the target gene by interaction with its 3’untranslated region (3′UTR). In this paper, we review the recent progress in the field, focusing on the association between miRNAs and oxidative stress during the progression of diabetes.

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