<i>In vivo</i> effects of <i>Cannabis sativa</i> L. extract on blood coagulation, fat and glucose metabolism in normal and streptozocin-induced diabetic rats

Abstract Background The use of Loranthus micranthus in folklore medicine for treatment of diabetes and its associated complications is a common practice around the world. The present study investigated this traditional affirmation by in vivo investigation into the effect of L. micranthus leaf extract on hepatic and renal, oxidative status and glucose metabolism in streptozotocin (STZ)-induced diabetic rats. Methods Diabetes mellitus was induced in adult male Wistar rats by intraperitoneal injection of STZ (60 mg/kg). The diabetic rats were thereafter treated orally once per day with 5 mg/kg gilbenclamide or L. micranthus leaf extract (100 or 200 mg/kg) and monitored for 14 days. Clinical observations, plasma biochemistry, hormonal profile, oxidative stress parameters, glucose metabolism enzymes and histopathologic examination of the liver and kidney were evaluated to monitor treatment-related effects of L. micranthus leaf extract in STZ-induced diabetic rats. Results Loranthus micranthus leaf extract administration significantly ameliorated hyperglycemia-mediated damage by decreasing the blood glucose level (45.9% and 84.7% on days 7 and 14 posttreatment, respectively), enhancing the antioxidant status, inhibiting lipid peroxidation and improving the architecture of the liver and kidney in STZ-induced diabetic rats. Furthermore, intervention of L. micranthus leaf extract restored the liver and kidney function biomarkers and increased the plasma levels of triiodothyronine and thyroxine to normal control in STZ-induced diabetic rats. Conclusions The findings from this investigation provide credible scientific support for the traditional use of L. micranthus leaf extract in the treatment of diabetes and its associated complications.

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Diabetes-induced alterations of glucose metabolism in rat cerebral microvessels

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1984.247.4.e462 ◽

1984 ◽

Vol 247 (4) ◽

pp. E462-E467 ◽

Cited By ~ 1

Author(s):

A. L. McCall ◽

J. B. Gould ◽

N. B. Ruderman

Keyword(s):

Blood Glucose ◽

Glucose Metabolism ◽

Insulin Therapy ◽

Blood Brain Barrier ◽

Diabetic Rats ◽

Brain Barrier ◽

Cerebral Microvessels ◽

Blood Brain ◽

Brain Uptake Index

The effect of diabetes on the metabolism of glucose and lactate was examined in isolated rat cerebral microvessels. In rats with diabetes induced with streptozotocin, glucose oxidation to CO2 by the microvessels was decreased by 54-83% and its conversion to lactate by 21-61%. Insulin therapy for several days or starvation for 48 h both lowered blood glucose levels in the diabetic rats and restored microvessel glucose metabolism to normal. Cerebral microvessels consist principally of the capillaries that constitute the blood-brain barrier. Direct assessment of the blood-brain barrier in vivo using the brain uptake index (BUI) technique revealed a close parallel to the findings in the microvessels. Thus, hexose transport was diminished in diabetic rats and restored to normal by both insulin therapy and starvation. The oxidation of [1-14C]lactate to CO2 like that of glucose was depressed in microvessels of diabetic rats. In contrast to glucose, however, the transport of lactate across the blood-brain barrier in vivo was not altered. These findings suggest that diabetes suppresses glucose metabolism in rat cerebral microvessels and downregulates glucose transport across the blood-brain barrier. They also suggest that both of these processes are regulated by chronic alterations in blood glucose concentration rather than by insulin per se.

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Analysis of glucose metabolism in diabetic rat retinas

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00323.2005 ◽

2006 ◽

Vol 290 (6) ◽

pp. E1057-E1067 ◽

Cited By ~ 57

Author(s):

M. Shamsul Ola ◽

Deborah A. Berkich ◽

Yuping Xu ◽

M. Todd King ◽

Thomas W. Gardner ◽

...

Keyword(s):

Oxidative Stress ◽

Glucose Metabolism ◽

Tricarboxylic Acid Cycle ◽

Lactate Production ◽

Tricarboxylic Acid ◽

Diabetic Rats ◽

Glycolytic Flux ◽

Acid Cycle

This study was conceived in an effort to understand cause and effect relationships between hyperglycemia and diabetic retinopathy. Numerous studies show that hyperglycemia leads to oxidative stress in the diabetic retinas, but the mechanisms that generate oxidative stress have not been resolved. Increased electron pressure on the mitochondrial electron transfer chain, increased generation of cytosolic NADH, and decreases in cellular NADPH have all been cited as possible sources of reactive oxygen species and nitrous oxide. In the present study, excised retinas from control and diabetic rats were exposed to euglycemic and hyperglycemic conditions. Using a microwave irradiation quenching technique to study retinas of diabetic rats in vivo, glucose, glucose-derived metabolites, and NADH oxidation/reduction status were measured. Studying excised retinas in vitro, glycolytic flux, lactate production, and tricarboxylic acid cycle flux were evaluated. Enzymatically assayed glucose 6-phosphate and fructose 6-phosphate were only slightly elevated by hyperglycemia and/or diabetes, but polyols were increased dramatically. Cytosolic NADH-to-NAD ratios were not elevated by hyperglycemia nor by diabetes in vivo or in vitro. Tricarboxylic acid cycle flux was not increased by the diabetic state nor by hyperglycemia. On the other hand, small increases in glycolytic flux were observed with hyperglycemia, but glycolytic flux was always lower in diabetic compared with control animals. An observed decrease in activity of glyceraldehyde-3-phosphate dehydrogenase may be partially responsible for slow glycolytic flux for retinas of diabetic rats. Therefore, it is concluded that glucose metabolism, downstream of hexokinase, is not elevated by hyperglycemia or diabetes. Metabolites upstream of glucose such as the sorbitol pathway (which decreases NADPH) and polyol synthesis are increased.

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In vivo assessment of hypoglycaemic and antioxydant activities of aqueous extract of Terminalia superba in alloxan-diabetic rats

Planta Medica ◽

10.1055/s-0029-1234718 ◽

2009 ◽

Vol 75 (09) ◽

Author(s):

NEC Momo ◽

EJ Oben

Keyword(s):

Aqueous Extract ◽

Diabetic Rats ◽

Terminalia Superba ◽

In Vivo Assessment

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The Natural Course of Defibrination Syndrome Caused by Echis Colorata Venom in Man

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649181 ◽

1974 ◽

Vol 31 (03) ◽

pp. 420-428 ◽

Cited By ~ 3

Author(s):

M Fainaru ◽

S Eisenberg ◽

N Manny ◽

C Hershko

Keyword(s):

Factor Viii ◽

Blood Coagulation ◽

Major Bleeding ◽

Renal Damage ◽

Specific Treatment ◽

Natural Course ◽

Factor V ◽

Thrombocyte Count

SummaryThe natural course of defibrination syndrome caused by Echis colorata venom (ECV) in five patients is reported. All patients developed afibrinogenemia within six hours after the bite. Concomitantly a depression in factor V was recorded. Factor VIII and thrombocyte count in blood were normal in most patients. In the light of the known effects of ECV on blood coagulation in vivo and in vitro it is concluded that the afibrinogenemia is due to intravascular clotting.Four patients had transient renal damage, manifested by oliguria, azotemia, albuminuria and cylindruria, ascribed to microthrombi in the renal glomeruli.After the bite, the natural course was benign, no major bleeding was observed, and all signs of coagulopathy reverted to normal within 7 days. Therefore we recommend no specific treatment for this condition. In the case of heavily bleeding patients, administration of antiserum against ECV and/or heparin should be considered.

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Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

Melatonin Research ◽

10.32794/mr11250042 ◽

2019 ◽

Vol 2 (4) ◽

pp. 83-98 ◽

Cited By ~ 2

Author(s):

André De Lima Mota ◽

Bruna Vitorasso Jardim-Perassi ◽

Tialfi Bergamin De Castro ◽

Jucimara Colombo ◽

Nathália Martins Sonehara ◽

...

Keyword(s):

Breast Cancer ◽

Glucose Metabolism ◽

Tumor Growth ◽

Tumor Cells ◽

Carbonic Anhydrases ◽

In Vivo Models ◽

Ca Ix ◽

Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression.

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