scholarly journals Galangin Attenuates Liver Injury, Oxidative Stress and Inflammation, and Upregulates Nrf2/HO-1 Signaling in Streptozotocin-Induced Diabetic Rats

Processes ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1562
Author(s):  
Wesam Al-Amarat ◽  
Mohammad H. Abukhalil ◽  
Osama Y. Althunibat ◽  
Manal A. Alfwuaires ◽  
Mashael M. Alnamshan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Inflammatory Response ◽  
Glucose Intolerance ◽  
Serum Insulin ◽  
Liver Glycogen ◽  
Diabetic Rats ◽  
Histopathological Alterations ◽  
Chronic Hyperglycemia ◽  
Cellular Antioxidants

Chronic hyperglycemia increases the risk of liver damage. Oxidative stress and aberrant inflammatory response are entangled in diabetes-associated liver injury. This study evaluated the protective effect of the flavonoid galangin (Gal) on glucose intolerance, liver injury, oxidative stress, inflammatory response, and Nrf2/HO-1 signaling in diabetic rats. Diabetes was induced by streptozotocin (STZ), and the rats received Gal for six weeks. STZ-induced rats showed glucose intolerance, hypoinsulinemia, elevated glycated hemoglobin (HbA1c), and decreased liver glycogen. Gal ameliorated glucose intolerance, reduced HbA1c%, increased serum insulin and liver glycogen and hexokinase activity, and suppressed glycogen phosphorylase, glucose-6-phosphatase and fructose-1,6-biphosphatase in diabetic rats. Circulating transaminases, ALP and LDH, and liver ROS, MDA, TNF-α, IL-1β, and IL-6 were increased and GSH, SOD, and CAT were diminished in diabetic rats. In addition, diabetic rats exhibited multiple histopathological alterations and marked collagen deposition. Treatment with Gal mitigated liver injury, prevented histopathological alterations, decreased ROS, MDA, pro-inflammatory cytokines, Bax and caspase-3, and enhanced cellular antioxidants and Bcl-2. Gal downregulated hepatic Keap1 in diabetic rats and upregulated Nrf2 and HO-1 mRNA as well as HO-1 activity. Molecular modeling studies revealed the ability of Gal to bind to and inhibit NF-κB and Keap1, and also showed its binding pattern with HO-1. In conclusion, Gal ameliorates hyperglycemia, glucose intolerance, oxidative stress, inflammation, and apoptosis in diabetic rats. Gal improved carbohydrate metabolizing enzymes and upregulated Nrf2/HO-1 signaling.

scholarly journals Allopurinol ameliorates liver injury in type 1 diabetic rats through activating Nrf2

2021 ◽  
Vol 35 ◽  
pp. 205873842110314
Author(s):  
Fei Zeng ◽  
Jierong Luo ◽  
Hong Han ◽  
Wenjie Xie ◽  
Lingzhi Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Caspase 3 ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Heme Oxygenase 1 ◽  
Liver Protein ◽  
Lipid Peroxidation Product ◽  
Protein Expressions

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.

scholarly journals Antidiabetic potential of the leaf extract of Centella asiatica in alloxaninduced diabetic rats

2016 ◽  
Vol 4 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Talha Bin Emran ◽  
Mycal Dutta ◽  
Mir Muhammad Nasir Uddin ◽  
Aninda Kumar Nath ◽  
Md Zia Uddin
Keyword(s):  
Body Weight ◽  
Leaf Extract ◽  
Total Cholesterol Level ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Centella Asiatica ◽  
Liver Glycogen ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Diabetic Rat

The study was designed to evaluate the glucose and cholesterol lowering effect of the aqueous extract of Centella asiatica leaf using the alloxan-induced diabetic rats and compared the activity with diabetic control and antidiabetic drug (Glibenclamide). Leaf extract (50 mg/kg) of C. asiatica and Glibenclamide were administered to normal and experimental diabetic rats for the duration of 10 days. In the alloxan-induced diabetic rat model, C. asiatica extract (50 mg/kg) significantly (p < 0.05) lowered the fasting blood glucose level as well as the total cholesterol level. Serum insulin levels were not stimulated in the animals treated with the extract. In addition, changes in body weight, serum lipid profiles and liver glycogen levels assessed in the extract treated diabetic rats were compared with diabetic control and normal animals. Significant results (p < 0.05) were observed in the estimated parameters. Surprisingly, body weight was increased significantly (p < 0.05) in the C. asiatica treated diabetic group. Phytochemical screening showed the presence of alkaloids, flavonoids, glycosides, steroids and tannins in significant amountsJahangirnagar University J. Biol. Sci. 4(1): 51-59, 2015 (June)

Shivering thermogenesis and glucose uptake by muscles of normal or diabetic rats

1982 ◽  
Vol 242 (1) ◽  
pp. R109-R115 ◽  
Author(s):  
O. L. Smith ◽  
S. B. Davidson
Keyword(s):  
Glucose Uptake ◽  
Plasma Glucose ◽  
Serum Insulin ◽  
Liver Glycogen ◽  
Diabetic Rats ◽  
Glucose Levels ◽  
Severe Diabetes ◽  
Mild Diabetes ◽  
Fasted Rats ◽  
Shivering Thermogenesis

Acute cold exposure of normal rats (4 degrees C for 24 h) increased food intake, reduced plasma glucose and liver glycogen, caused a small increase in plasma free fatty acids, and lowered serum insulin concentration by 50%. In fasted rats, cold raised fatty acid levels twice as high as in fed. In mild diabetes (40 mg/kg streptozotocin iv) cold reduced glucose levels in blood and urine, but in severe diabetes (90 mg/kg) cold aggravated hyperglycemia and ketonuria. Changes in muscle glucose utilization were also studied, after evisceration (functional hepatectomy) of rats from each group. Uptake was calculated from the fall in plasma glucose concentration during the 4-h period after a load of 50% glucose iv. Cold normally increased uptake 67%, but it failed to do so in fasted rats. In diabetic rats, cold enhanced uptake, but only if the disease were mild or insulin controlled. Sensitivity of uptake to insulin was unaffected by cold. The results suggest that shivering thermogenesis, like exercise, can promote glucose uptake by skeletal muscle, if enough insulin is present to prevent excess mobilization of lipid substrates.

scholarly journals Pleurotus tuber-regiumPolysaccharides Attenuate Hyperglycemia and Oxidative Stress in Experimental Diabetic Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hui-Yu Huang ◽  
Mallikarjuna Korivi ◽  
Ying-Ying Chaing ◽  
Ting-Yi Chien ◽  
Ying-Chieh Tsai
Keyword(s):  
Oxidative Stress ◽  
Serum Insulin ◽  
Glycosylated Hemoglobin ◽  
Low Density Lipoprotein ◽  
Fasting Blood Glucose ◽  
Antioxidant Properties ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
High Fat ◽  
And Oxidative Stress

Pleurotus tuber-regiumcontains polysaccharides that are responsible for pharmacological actions, and medicinal effects of these polysaccharides have not yet been studied in diabetic rats. We examined the antidiabetic, antihyperlipidemic, and antioxidant properties ofP. tuber-regiumpolysaccharides in experimental diabetic rats. Forty rats were equally assigned as diabetic high-fat (DHF) diet and polysaccharides treated DHF groups (DHF+1P, DHF+2P, and DHF+3P, 20 mg/kg bodyweight/8-week). Diabetes was induced by chronic low-dose streptozotocin injections and a high-fat diet to mimic type 2 diabetes. Polysaccharides (1P, 2P, and 3P) were extracted from three different strains ofP. tuber-regium. Fasting blood glucose and glycosylated hemoglobin (HbA1c) levels substantially decreased, while serum insulin levels were restored by polysaccharides treatment compared to DHF. Furthermore, plasma total cholesterol, triglycerides, and low-density lipoprotein levels were significantly(P<0.01)lower in polysaccharide groups. High-density lipoprotein levels were attenuated with polysaccharides against diabetes condition. Polysaccharides inhibited(P<0.01)the lipid peroxidation index (malondialdehyde), and restored superoxide dismutase and glutathione peroxidase activities in the liver of diabetic rats. The antihyperglycemic property of polysaccharides perhaps boosts the antioxidant system that attenuates oxidative stress. We emphasize thatP. tuber-regiumpolysaccharides can be considered as an alternative medicine to treat hyperglycemia and oxidative stress in diabetic rats.

scholarly journals Effects of L-glutamine supplementation on the myenteric neurons from the duodenum and cecum of diabetic rats

2011 ◽  
Vol 48 (1) ◽  
pp. 66-71 ◽  
Author(s):  
Jacqueline Nelisis Zanoni ◽  
Eleandro Aparecido Tronchini ◽  
Sheila Alves Moure ◽  
Ivan Domicio da Silva Souza
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Neuroprotective Effect ◽  
Natural Aging ◽  
Neurological Complications ◽  
Diabetic Rats ◽  
Glutamine Supplementation ◽  
Complications Of Diabetes ◽  
Myenteric Neurons ◽  
Cellular Antioxidants

CONTEXT: Peripheral neuropathy is one of the chronic complications of diabetes mellitus and is directly related to gastrointestinal consequences of the disease. Myenteric neurons are affected in some pathological conditions such as diabetic neuropathy. The imbalance between cellular antioxidants and free radicals, leading to an increase in oxidative stress, is considered one of the main factors responsible for neuronal damages in diabetes. Drugs that reduce the oxidative stress may play a significant role in the treatment of neurological complications of diabetes mellitus. OBJECTIVE: To evaluate the effect of L-glutamine supplementation on the myenteric neurons from the cecum and duodenum of Wistar rats with streptozotocin-induced diabetes mellitus. METHODS: The animals were divided in four groups (n = 5): non-treated normoglycemics, normoglycemics treated with L-glutamine, non-treated diabetics and diabetics treated with L-glutamine from the 4th day of diabetes induction on. The amino acid L-glutamine was added to their diet at 1%. Giemsa's technique was employed to stain the myenteric neurons. We determined the cell body area of 500 neurons in each group studied. The quantitative analysis was performed by sampling in an area of 16.6 mm² in the cecum and 3.6 mm² in the duodenum of each animal. RESULTS: After the supplementation with L-glutamine in the duodenum, we observed a preservation of neuronal density in groups normoglycemic and diabetic (P<0.05). We also observed a preservation of the cell bodies area in diabetic animals (group treated with L-glutamine) (P<0.05). In the cecum, that preservation was not evident. CONCLUSION: Supplementation with L-glutamine (1%) promoted a neuroprotective effect on the myenteric neurons from the duodenum of rats, both in terms of natural aging and of diabetes mellitus.

Testosterone promotes glucose intolerance, lipid disorder and oxidative stress in type 1 diabetic rats

2014 ◽  
Vol 25 (1) ◽  
Author(s):  
Ayodele Olufemi Morakinyo ◽  
Daniel Abiodun Adekunbi ◽  
Kayode Akanni Dada ◽  
Olufeyi Adefunke Adegoke
Keyword(s):  
Oxidative Stress ◽  
Glucose Intolerance ◽  
Diabetic Rats ◽  
Lipid Disorder ◽  
And Oxidative Stress
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