scholarly journals Glycation and inactivation of sorbitol dehydrogenase in normal and diabetic rats

1996 ◽  
Vol 318 (1) ◽  
pp. 119-123 ◽  
Author(s):  
Ayumu HOSHI ◽  
Motoko TAKAHASHI ◽  
Junichi FUJII ◽  
Theingi MYINT ◽  
Hideaki KANETO ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Diabetic Complications ◽  
Polyol Pathway ◽  
Diabetic Rats ◽  
Sorbitol Dehydrogenase ◽  
Enzyme Content ◽  
Glycated Protein ◽  
Liver And Kidney

Sorbitol dehydrogenase (SDH) is involved in the polyol pathway, which plays an important role in the pathogenesis of diabetic complications. We have measured the tissue distributions of SDH mRNA, both the immunoreactive enzyme levels and the enzyme activity. SDH mRNA was especially abundant in liver, kidney and testis. Both the activity and enzyme content are high in liver and kidney but not in testis. The discrepancy between mRNA and immunoreactive enzyme levels and the activity of SDH observed in testis was also seen in livers of streptozotocin-induced diabetic rats. SDH was found to exist in both glycated and non-glycated forms, with larger amounts of the glycated protein in the diabetic liver. Moreover, after incubation of purified enzyme with glucose or fructose, its activity was markedly decreased. These results indicate that glycation causes a decrease in SDH activity in liver under diabetic conditions. The same post-transcriptional event might occur to decrease the activity of SDH in testis in normal animals.

Laurus nobilis Linn. Inhibits Polyol Pathway Enzymes: Strategy for Managing Diabetic Complications

2021 ◽  
Vol 17 ◽  
Author(s):  
Habeeb Adebodun Bankole ◽  
Azeez Ayomide Fatai ◽  
Sulihat Motunrayo Aleshe ◽  
Mutiu Idowu Kazeem ◽  
Abidemi Paul Kappo
Keyword(s):  
Aldose Reductase ◽  
Diabetic Complications ◽  
Curcuma Longa ◽  
Polyol Pathway ◽  
Sorbitol Dehydrogenase ◽  
Thymus Vulgaris ◽  
Laurus Nobilis ◽  
Pharmacological Agents ◽  
Rising Incidence ◽  
Inhibitory Potential

Background: The rising incidence of diabetic complications necessitate the continuous search for safer, cheaper and effective pharmacological agents. Polyol pathway is an underlying process implicated in the pathogenesis of diabetic complications. Inhibition of enzymes in the polyol pathway is a veritable means of ameliorating diabetic complications. Objective: This study evaluated the inhibitory potential of some spicy plants on the activities of polyol pathway enzymes (aldose reductase and sorbitol dehydrogenase). Method: Aqueous extracts of Laurus nobilis (bay), Cinnamomum zeylanicum (cinnamon), Murraya koenigii (curry), Thymus vulgaris (thyme) and Curcuma longa (turmeric) were incubated with appropriate enzymes and substrates, and percentages inhibition determined. Results: Results showed that bay extract had effective IC50 for inhibition of both aldose reductase (174.87 µg/mL) and sorbitol dehydrogenase (37.08 µg/mL). It also revealed that bay extract inhibited aldose reductase and sorbitol dehydrogenase in a non-competitive and competitive manner respectively. Conclusion: It is therefore concluded that bay extract effectively inhibited activities of polyol pathway enzymes, and may contribute to the amelioration of diabetic complications.

scholarly journals Bitter Gourd Honey Ameliorates Hepatic and Renal Diabetic Complications on Type 2 Diabetes Rat Models by Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms

Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2872
Author(s):  
Chandra Sekhar Arigela ◽  
Giribabu Nelli ◽  
Siew Hua Gan ◽  
Kuttulebbai Nainamohamed Salam Sirajudeen ◽  
Kumarathevan Krishnan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Complications ◽  
Diabetic Rats ◽  
Male Rats ◽  
Bitter Gourd ◽  
Liver And Kidney ◽  
Streptozotocin Induced Diabetes ◽  
Treatment Of Diabetes ◽  
Anti Inflammatory ◽  
Apoptotic Effects

Honey has several pharmacological effects, including anti-diabetic activity. However, the effectiveness of bitter gourd honey (BGH) in the treatment of diabetes mellitus (DM) is unknown. The aim of this study was to determine the antioxidant, anti-inflammatory, and anti-apoptotic properties of BGH on the kidney and liver of a streptozotocin-induced diabetes rat model. Methods: A single dose (nicotinamide 110 mg/kg, streptozotocin (STZ) 55 mg/kg, intraperitoneal (i.p.)) was used to induce DM in male rats. For 28 days, normal or diabetic rats were administered 1 g/kg/day and 2 g/kg/day of BGH orally. After the treatment, blood, liver, and kidney samples were collected and analysed for biochemical, histological, and molecular parameters. In addition, liquid chromatography–mass spectrometry (LC-MS) was used to identify the major bioactive components in BGH. Results: The administration of BGH to diabetic rats resulted in significant reductions in alanine transaminase (ALT),aspartate aminotransferase (AST), creatinine, and urea levels. Diabetic rats treated with BGH showed lesser pathophysiological alterations in the liver and kidney as compared to non-treated control rats. BGH-treated diabetic rats exhibited reduced levels of oxidative stress (MDA levels), inflammatory (MYD88, NFKB, p-NFKB, IKKβ), and apoptotic (caspase-3) markers, as well as higher levels of antioxidant enzymes (SOD, CAT, and GPx) in the liver and kidney. BGH contains many bioactive compounds that may have antioxidative stress, anti-inflammatory, and anti-apoptotic effects. Conclusion: BGH protected the liver and kidney in diabetic rats by reducing oxidative stress, inflammation, and apoptosis-induced damage. As a result, BGH can be used as a potential therapy to ameliorate diabetic complications.

scholarly journals A Novel Carboxymethylated Mercaptotriazinoindole Inhibitor of Aldose Reductase Interferes With the Polyol Pathway in Streptozotocin-Induced Diabetic Rats

2015 ◽  
pp. 587-591 ◽  
Author(s):  
M. SOLTESOVA PRNOVA ◽  
J. BALLEKOVA ◽  
A. GAJDOSIKOVA ◽  
A. GAJDOSIK ◽  
M. STEFEK
Keyword(s):  
Sciatic Nerve ◽  
Aldose Reductase ◽  
Experimental Diabetes ◽  
Polyol Pathway ◽  
Diabetic Rats ◽  
Sorbitol Dehydrogenase ◽  
Substrate Affinity ◽  
Back Reaction ◽  
Forward Reaction

The aim of the present work was to study the effect of 3-mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid (CMTI), an efficient aldose reductase inhibitor, on sorbitol accumulation in selected organs of streptozotocin-induced diabetic rats in vivo. In addition, the effect of CMTI on aldose reductase back reaction and on sorbitol dehydrogenase was determined. The model of experimental diabetes in male Wistar rats induced by streptozotocin was used. Experimental diabetes was induced by triple intraperitoneal doses of streptozotocin on three consecutive days. In diabetic rats, significant elevation of sorbitol concentration in the sciatic nerve and eye lenses was recorded. CMTI administered intragastrically (50 mg/kg/day) for five consecutive days significantly inhibited sorbitol accumulation in the sciatic nerve, yet it was without effect in eye lenses of diabetic animals. For aldose reductase back reaction, the substrate affinity of glycerol to aldose reductase was one order lower than that of glyceraldehyde in forward reaction. In addition, the back reaction was much slower, characterized by Vmax value of about 30 times lower than that of the forward reaction. Inhibition of aldose reductase by CMTI was characterized by closely related IC50 values in submicromolar range for both forward and back reactions. No significant inhibition of the second enzyme of the polyol pathway, sorbitol dehydrogenase, by 100 μM CMTI was recorded (I=0.9±2.7 %, n=3). To conclude, the presented results showed the ability of CMTI to affect the polyol pathway in diabetic rats in vivo and represent thus a further step in a complex preclinical evaluation of CMTI as a potential agent for treatment of chronic diabetic complications.

Beneficial influence of fungal metabolite nigerloxin on eye lens abnormalities in experimental diabetes

2012 ◽  
Vol 90 (4) ◽  
pp. 387-394 ◽  
Author(s):  
Bharathinagar S. Suresha ◽  
Avinash P. Sattur ◽  
Krishnapura Srinivasan
Keyword(s):  
Aldose Reductase ◽  
Radical Scavenging ◽  
Lipid Peroxides ◽  
Antioxidant Defense System ◽  
Polyol Pathway ◽  
Diabetic Rats ◽  
Sorbitol Dehydrogenase ◽  
Eye Lens ◽  
Fungal Metabolite

Osmotic and oxidative stress have been implicated in the pathogenesis of diabetic cataract. Nigerloxin, a fungal metabolite, has been shown to possess aldose reductase inhibitory and free radical scavenging potential, in vitro. In the present study, the beneficial influence of nigerloxin was investigated on diabetes-induced alteration in the eye lens of rats treated with streptozotocin. Groups of diabetic rats were administered nigerloxin orally (100 mg·(kg body mass)–1·day–1) for 30 days. The activity of lens polyol pathway enzymes (aldose reductase and sorbitol dehydrogenase), lipid peroxides, and advanced glycation end products (AGEs) were increased in the diabetic animals. Levels of glutathione as well as the activity of antioxidant enzymes (superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase) were decreased in the eye lens of the diabetic animals. The administration of nigerloxin significantly decreased levels of lipid peroxides and AGEs in the lens of the diabetic rats. Increase in the activity of aldose reductase and sorbitol dehydrogenase in the lens was countered by nigerloxin treatment. The activity of glutathione and antioxidant enzyme in the lens was significantly elevated in nigerloxin-treated diabetic rats. Examination of the treated rats’ eyes indicated that nigerloxin delayed cataractogenesis in the diabetic rats. The results suggest the beneficial countering of polyol pathway enzymes and potentiation of the antioxidant defense system by nigerloxin in diabetic animals, implicating its potential in ameliorating cataracts in diabetics.

scholarly journals Quantification of liver and kidney phosphofructokinase by radioimmunoassay in fed, starved and alloxan-diabetic rats

1984 ◽  
Vol 224 (2) ◽  
pp. 541-547 ◽  
Author(s):  
J C Donofrio ◽  
R S Thompson ◽  
G D Reinhart ◽  
C M Veneziale
Keyword(s):  
Specific Activity ◽  
Liver Weight ◽  
Diabetic Rats ◽  
Liver Size ◽  
Fed State ◽  
Enzyme Content ◽  
Activity Measurements ◽  
Kidney Enzyme ◽  
Liver And Kidney ◽  
Total Enzyme

A newly developed specific radioimmunoassay was used to quantify phosphofructokinase protein directly and independently of assayable activity in liver and kidney cytosol of normal fed, starved and alloxan-diabetic rats. In the fed state, liver phosphofructokinase concentration was 0.096 microM and the kidney enzyme was 0.086 microM (mumol/kg of tissue). In the starved state (24h), liver and kidney phosphofructokinase concentrations decreased by 30%. Prolonged starvation up to 72h did not further decrease enzyme concentration. In liver, total enzyme content during starvation declined by more than 50%, secondary also to a decrease in liver weight. In the alloxan-diabetic rats, there was a 22% decrease in enzyme protein concentration in liver and kidney. Total enzyme content per liver actually decreased much more (46%), because diabetes also resulted in a decrease in liver size. In conjunction with assayable activity measurements, the results of the radioimmunoassay allowed us to calculate the apparent specific activity of the enzyme. The specific activity of the kidney enzyme was 2-3 times that of the liver. Little or no change in specific activity of the liver or kidney enzyme occurred as a result of starvation or chemically induced diabetes. Tissue enzyme concentrations of phosphofructokinase unequivocally reconcile the ultimate results of changing rates of synthesis and degradation and are useful data in the design of spectrophotometric, kinetic, aggregation-disaggregation and other studies.

scholarly journals Carica papaya Linn. fruit extract inhibited the activities of aldose reductase and sorbitol dehydrogenase: possible mechanism for amelioration of diabetic complications

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Mutiu Idowu Kazeem ◽  
Ayotomiwa Adeyinka Adeyemi ◽  
Abiola Fatimah Adenowo ◽  
Mushafau Adewale Akinsanya
Keyword(s):  
Aldose Reductase ◽  
Aqueous Extract ◽  
Diabetic Complications ◽  
Carica Papaya ◽  
Citrullus Lanatus ◽  
Polyol Pathway ◽  
Inhibitory Effect ◽  
Sorbitol Dehydrogenase ◽  
Diabetic Foot Disease ◽  
Foot Disease

Abstract Background Diabetes mellitus is a metabolic disorder which is associated with debilitating complications including eye disease, kidney disorder, and diabetic foot disease. One of the mechanisms implicated in the pathogenesis of diabetic complications is the polyol pathway. This study evaluated the inhibitory effect of aqueous extract of four tropical fruits, namely apple (Malus domestica Borkh.), banana (Musa paradisiaca Linn.), pawpaw (Carica papaya Linn.), and watermelon (Citrullus lanatus (Thunb.) Matsum & Nakai), on the activities of polyol pathway enzymes (aldose reductase and sorbitol dehydrogenase). Results All the fruits, with the exception of banana, displayed stronger inhibition of sorbitol dehydrogenase than aldose reductase which culminated in low IC50 for the inhibition of sorbitol dehydrogenase. Of the fruit extracts tested, pawpaw inhibited both aldose reductase and sorbitol dehydrogenase most effectively with IC50 of 150.78 μg/mL and 46.30 μg/mL, respectively. Lineweaver-Burk plot also revealed that the pawpaw extract inhibited aldose reductase competitively while sorbitol dehydrogenase was inhibited in a mixed non-competitive manner. Conclusion Aqueous extract of pawpaw fruit effectively inhibited polyol pathway enzymes, and this may be attributed to rich nutritional and phytochemical composition of the fruit. Consequently, the consumption of pawpaw fruit may contribute to the amelioration of diabetic complications.

Eudragit L-100 Capsules Aromatize and Quaternerize Chitosan for Insulin Nanoparticle Oral Delivery During Toxic Oxidative Stress in Rat Liver and Kidney

2020 ◽  
Vol 8 (3) ◽  
pp. 239-254 ◽  
Author(s):  
Reza Mahjub ◽  
Farzane K. Najafabadi ◽  
Narges Dehkhodaei ◽  
Nejat Kheiripour ◽  
Amir N. Ahmadabadi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oral Administration ◽  
Oral Delivery ◽  
Biochemical Parameters ◽  
Kidney Injury ◽  
Regular Insulin ◽  
Treated Group ◽  
Histopathological Change ◽  
Diabetic Rats ◽  
Liver And Kidney

Background: Insulin, like most peptides, is classified as a hydrophilic and macromolecular drug that is considered as a low permeable and unstable compound in the gastrointestinal (GI) tract. The acidic condition of the stomach can degrade insulin molecules. Moreover, the presence of proteolytic activities of some enzymes such as trypsin and chymotrypsin can hydrolyze amide-bonds between various amino-acids in the structures of peptides and proteins. However, due to its simplicity and high patient compliance, oral administration is the most preferred route of systemic drug delivery, and for the development of an oral delivery system, some obstacles in oral administration of peptides and proteins including low permeability and low stability of the proteins in GI should be overcome. Objective: In this study, the effects of orally insulin nanoparticles (INPs) prepared from quaternerized N-aryl derivatives of chitosan on the biochemical factors of the liver in diabetic rats were studied. Methods: INPs composed of methylated (amino benzyl) chitosan were prepared by the PEC method. Lyophilized INPs were filled in pre-clinical capsules, and the capsules were enteric-coated with Eudragit L100. Twenty Male Wistar rats were randomly divided into four groups: group1: normal control rats, group 2: diabetic rats, group 3: diabetic rats received capsules INPs(30 U/kg/day, orally), group 4: the diabetic rats received regular insulin (5 U/kg/day, subcutaneously). At the end of the treatment, serum, liver and kidney tissues were collected. Biochemical parameters in serum were measured using spectrophotometric methods. Also, oxidative stress was measured in plasma, liver and kidney. Histological studies were performed using H and E staining . Results: Biochemical parameters, and liver and kidney injury markers in serum of the diabetic rats that received INPs improved significantly compared with the diabetic group. INPs reduced oxidative toxic stress biomarkers in serum, liver and kidney of the diabetic treated group. Furthermore, a histopathological change was developed in the treated groups. Conclusion: Capsulated INPs can prevent diabetic liver and oxidative kidney damages (similar regular insulin). Therefore oral administration of INPs appears to be safe. Lay Summary: Although oral route is the most preferred route of administration, but oral delivery of peptides and proteins is still a challenging issue. Diabetes Mellitus may lead to severe complications, which most of them are life-threatening. In this study, we are testing the toxicity of oral insulin nanoparticles in kidney and liver of rats. For this investigation, we will prepare insulin nanoparticles composed of a quaternized derivative of chitosan. The nanoparticles will be administered orally to rats and the level of oxidative stress in their liver and kidney will be determined. The data will be compared to the subcutaneous injection of insulin.

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