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

Hyperglycemia-induced oxidative stress plays important roles in the development of non-alcoholic fatty liver disease (NAFLD), which is a common complication in diabetic patients. The Nrf2-Keap1 pathway is important for cell antioxidant protection, while its role in exogenous antioxidant mediated protection against NAFLD is unclear. We thus, postulated that antioxidant treatment with allopurinol (ALP) may attenuate diabetic liver injury and explored the underlying mechanisms. Control (C) and streptozotocin (STZ)-induced diabetes rats (D) were untreated or treated with ALP for 4 weeks starting at 1 week after diabetes induction. Serum levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), production of lipid peroxidation product malondialdehyde (MDA), and serum superoxide dismutase (SOD) were detected. Liver protein expressions of cleaved-caspase 3, IL-1β, nuclear factor-erythroid-2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), P62, Kelch-like ECH-associated protein 1 (Keap1), and LC3 were analyzed. In vitro, cultured rat normal hepatocytes BRL-3A were grouped to normal glucose (5.5 mM, NG) or high glucose (25 mM, HG) and treated with or without allopurinol (100 µM) for 48 h. Rats in the D group demonstrated liver injury evidenced as increased serum levels of ALT and AST. Diabetes increased apoptotic cell death, enhanced liver protein expressions of cleaved-caspase 3 and IL-1β with concomitantly increased production of MDA while serum SOD content was significantly reduced (all P < 0.05 vs C). In the meantime, protein levels of Nrf2, HO-1, and P62 were reduced while Keap1 and LC3 were increased in the untreated D group as compared to control ( P < 0.05 vs C). And all the above alterations were significantly attenuated by ALP. Similar to our findings obtained from in vivo study, we got the same results in in vitro experiments. It is concluded that ALP activates the Nrf2/p62 pathway to ameliorate oxidative stress and liver injury in diabetic rats.

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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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Effects of Hydroalcoholic Leaf Extract of Avicennia marina on Apoptotic, Inflammatory, Oxidative Stress, and Lipid Peroxidation Indices and Liver Histology of Type 1 Diabetic Rats

Hepatitis Monthly ◽

10.5812/hepatmon.99454 ◽

2020 ◽

Vol 20 (4) ◽

Author(s):

Seyed Damoon Sadoughi ◽

Seyed Morteza Hosseini

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Leaf Extract ◽

Avicennia Marina ◽

Diabetic Rats ◽

Liver Histology

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Curcumin attenuates oxidative stress in liver in Type 1 diabetic rats

Open Life Sciences ◽

10.1515/biol-2017-0053 ◽

2017 ◽

Vol 12 (1) ◽

pp. 452-459 ◽

Cited By ~ 3

Author(s):

Zhenglu Xie ◽

Xinqi Zeng ◽

Xiaqing Li ◽

Binbin Wu ◽

Guozhi Shen ◽

...

Keyword(s):

Oxidative Stress ◽

Polyol Pathway ◽

Diabetic Rats ◽

Diabetic Rat ◽

Curcumin Treatment ◽

Kinase C ◽

Diabetic Model ◽

Glucose 6 Phosphate Dehydrogenase ◽

Plasma Malondialdehyde

AbstractWe investigated the effect of curcumin on liver anti-oxidative stress in the type 1 diabetic rat model induced by streptozotocin (STZ). Experimental diabetic rats were induced by STZ intraperitoneally. All rats were fed for 21 days including three groups of control (NC), diabetic model (DC) and curcumin-treated (Cur, 1.5 g/kg by gavage). The results showed that curcumin-treatment significantly decreased the blood glucose and plasma malondialdehyde levels, but significantly increased the plasma superoxide dismutase, glutathione peroxidase and reduced glutathione levels. Curcumin treatment decreased the activity of aldose reductase, but increased the plasma glucose-6-phosphate dehydrogenase, glucose synthetase and glucose-polymerizing activities. Curcumin treatment significantly decreased the protein of protein kinase C (PKC) and poly ADP ribose polymerase (PARP) expression in the Cur group compared with the DC group. Moreover, the sorbitol dehydrogenase activity was significantly decreased and deterred glucose enters into the polyol pathway leading to an increased NADPH content in the Cur group compared with the DC group. Our data provides evidence that oxidative stress in diabetic rats may be attenuated by curcumin by inhibiting polyol pathway associated with down-regulated expression of PKC and PARP, as evidenced by both an increase the antioxidant enzymes levels and glycogen biosynthesis enzymes activities.

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Adeno-Associated Viral Transfer of Glyoxalase-1 Blunts Carbonyl and Oxidative Stresses in Hearts of Type 1 Diabetic Rats

Antioxidants ◽

10.3390/antiox9070592 ◽

2020 ◽

Vol 9 (7) ◽

pp. 592

Author(s):

Fadhel A. Alomar ◽

Abdullah Al-Rubaish ◽

Fahad Al-Muhanna ◽

Amein K. Al-Ali ◽

JoEllyn McMillan ◽

...

Keyword(s):

Oxidative Stress ◽

Ventricular Myocytes ◽

Diabetic Rats ◽

Confocal Imaging ◽

Glyoxalase 1 ◽

Microvascular Leakage ◽

Oxidative Stresses ◽

Rat Hearts ◽

Longitudinal Strains

Accumulation of methylglyoxal (MG) arising from downregulation of its primary degrading enzyme glyoxalase-1 (Glo1) is an underlying cause of diabetic cardiomyopathy (DC). This study investigated if expressing Glo1 in rat hearts shortly after the onset of Type 1 diabetes mellitus (T1DM) would blunt the development of DC employing the streptozotocin-induced T1DM rat model, an adeno-associated virus containing Glo1 driven by the endothelin-1 promoter (AAV2/9-Endo-Glo1), echocardiography, video edge, confocal imaging, and biochemical/histopathological assays. After eight weeks of T1DM, rats developed DC characterized by a decreased E:A ratio, fractional shortening, and ejection fraction, and increased isovolumetric relaxation time, E: e’ ratio, and circumferential and longitudinal strains. Evoked Ca2+ transients and contractile kinetics were also impaired in ventricular myocytes. Hearts from eight weeks T1DM rats had lower Glo1 and GSH levels, elevated carbonyl/oxidative stress, microvascular leakage, inflammation, and fibrosis. A single injection of AAV2/9 Endo-Glo1 (1.7 × 1012 viron particles/kg) one week after onset of T1DM, potentiated GSH, and blunted MG accumulation, carbonyl/oxidative stress, microvascular leakage, inflammation, fibrosis, and impairments in cardiac and myocyte functions that develop after eight weeks of T1DM. These new data indicate that preventing Glo1 downregulation by administering AAV2/9-Endo-Glo1 to rats one week after the onset of T1DM, blunted the DC that develops after eight weeks of diabetes by attenuating carbonyl/oxidative stresses, microvascular leakage, inflammation, and fibrosis.

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