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1.
Acta cir. bras ; 39: e390124, 2024. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1533360

ABSTRACT

Purpose: To determine the effect of gallic acid or its combination with glibenclamide on some biochemical markers and histology of the cornea of streptozotocin (STZ) induced diabetic rats. Methods: Following induction of diabetes, 24 male albino rats were divided into four groups of six rats each. Groups 1 and 2 (control and diabetic) received rat pellets and distilled water; group 3 (gallic acid) received rat pellets and gallic acid (10 mg/kg, orally) dissolved in the distilled water; and group 4 (gallic acid + glibenclamide) received rat pellets, gallic acid (10 mg/kg, orally), and glibenclamide (5 mg/kg, orally) dissolved in the distilled water. The treatments were administered for three months after which the rats were sacrificed after an overnight fast. Blood and sera were collected for the determination of biochemical parameters, while their eyes were excised for histology. Results: STZ administration to the rats induced insulin resistance, hyperglycemia, microprotenuria, loss of weight, oxidative stress, inflammation, and alteration of their cornea histology, which was abolished following supplementation with gallic acid or its combination with glibenclamide. Conclusions: The study showed the potentials of gallic acid and glibenclamide in mitigating systemic complication and histological changes in the cornea of diabetic rats induced with STZ.


Subject(s)
Animals , Rats , Glyburide/administration & dosage , Streptozocin/administration & dosage , Cornea/drug effects , Diabetes Mellitus , Gallic Acid/administration & dosage
2.
Braz. J. Pharm. Sci. (Online) ; 59: e21820, 2023. tab, graf
Article in English | LILACS | ID: biblio-1439542

ABSTRACT

ABSTRACT Diabetes is a life-threatening disease, and currently available synthetic medicines for treating diabetes are associated with various side effects. Therefore, there is an unmet need to develop herbal remedies against diabetes as an alternative to synthetic medicines. Although local healers use the roots of Spermadicyton suaveolens (SS) to manage diabetes, there is negligible research to validate its antidiabetic properties. The present investigation aims to the assess the antioxidant, antidiabetic, and antihyperlipidemic potential of the ethanolic extract of S. Suaveolen's roots (EESS) on streptozotocin (STZ) induced diabetic rats. The extract was screened for in vitro antioxidant and antidiabetic activity. The in vivo antidiabetic potential of EESS (at 200 and 400 mg/kg) was studied on STZ-induced diabetic rats for 20 days. The EESS displayed significant (p<0.05) antidiabetic and antioxidant properties. The administration of 200 mg/kg and 400 mg/kg EESS in STZ-induced diabetic rats significantly reduced hyperglycemia, and restored antioxidant enzymes and lipid profile-a high density lipoprotein (HDL) increased by the administration of a single dose of streptozotocin. Thus, EESS could be a promising herbal medicine in the treatment of diabetes and hyperlipidemia


Subject(s)
Animals , Male , Rats , Plant Extracts/analysis , Streptozocin/adverse effects , Diabetes Mellitus, Experimental/chemically induced , Hypoglycemic Agents/adverse effects , Antioxidants/pharmacology , In Vitro Techniques/methods , Herbal Medicine/classification , Phytotherapeutic Drugs , Synthetic Drugs/adverse effects , Hyperlipidemias/complications
3.
China Journal of Chinese Materia Medica ; (24): 1535-1545, 2023.
Article in Chinese | WPRIM | ID: wpr-970625

ABSTRACT

To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.


Subject(s)
Mice , Animals , Diabetes Mellitus, Type 2/genetics , Streptozocin/pharmacology , Diet, High-Fat/adverse effects , Proteomics , Inflammation , TOR Serine-Threonine Kinases , Autophagy , Mammals
4.
Braz. J. Pharm. Sci. (Online) ; 59: e21159, 2023. tab, graf
Article in English | LILACS | ID: biblio-1447571

ABSTRACT

Abstract Schiff bases are aldehyde-or ketone-like chemical compounds in which an imine or azomethine group replaces the carbonyl group. Such compounds show various beneficial biological activities, such as anti-inflammation and antioxidants. The present study addresses comprehensiveevaluation of antidiabetic effect of two novel dibromides and dichlorides substituted Schiff bases substituted Schiff bases (2,2'-[1,2-cyclohexanediylbis (nitriloethylidyne)]bis[4-chlorophenol] (CNCP) and 2, 2'-[1,2-cyclohexanediylbis(nitriloethylidyne)]bis[4-bromophenol] (CNBP) with two different doses, high (LD) and low (LD) in streptozotocin and nicotinamide induced diabetic rats. The rats were separated into normal, untreated, treated and reference groups. Except for the normal group, diabetes traits were induced in the rest animals. Insulin level was measured, and the effect of the compounds on biochemical parameters of liver function and lipid profile were evaluated. High glucose and decreased insulin level are observed in the groups. The histological evaluation confirms that the hepatic architecture in the treated animals with a low dose of CNCP is quite similar to that of the normal hepatic structure and characterized by normal central vein, hepatocytes without any fatty alterations and mild red blood cell infiltration. CNCP (LD) and CNBP (HD) are more successful in enhancing cell survival in the diabetic rat's liver and can be responsible for causing much healthier structure and notable morphology improvement.


Subject(s)
Animals , Male , Rats , Schiff Bases/agonists , Streptozocin/antagonists & inhibitors , Hypoglycemic Agents/adverse effects , Nicotinamidase/antagonists & inhibitors
5.
Acta cir. bras ; 38: e385623, 2023. graf
Article in English | LILACS, VETINDEX | ID: biblio-1527589

ABSTRACT

Purpose: Diabetes mellitus is a serious health problem worldwide, and diabetic nephropathy is the complication. The diabetic nephropathy considerably enhances the oxidative stress, glycation, lipid parameters and inflammatory reaction. Ellipticine has potent free radical scavenging and anti-inflammatory effect. Methods: In the current study, our objectives were to thoroughly examine the renal protective effects of ellipticine in a rat model of streptozotocin (STZ)-induced diabetic nephropathy (DN) and to elucidate the underlying mechanisms involved. For the induction of diabetic nephropathy, streptozotocin (50 mg/kg) was used, and rats were separated into groups and given varying doses of ellipticine (2.5, 5 and 7.5 mg/kg). The body weight, and renal weight were estimated. The inflammatory cytokines, renal biomarkers, inflammatory antioxidant, and urine parameters were estimated. Results: Result showed that ellipticine considerably enhanced the body weight and reduced the renal tissue weight. Ellipticine treatment significantly (P < 0.001) repressed the level of blood urea nitrogen, serum creatinine, uric acid, blood glucose and altered the lipid parameters. Ellipticine significantly (P < 0.001) repressed the level of malonaldehyde and boosted the glutathione, catalase, superoxide dismutase, and glutathione peroxidase. Ellipticine treatment significantly (P < 0.001) reduced the inflammatory cytokines and inflammatory mediators. Conclusions: Ellipticine could be a renal protective drug via attenuating the inflammatory reaction, fibrosis and oxidative stress in streptozotocin induced rats.


Subject(s)
Animals , Rats , Streptozocin , Oxidative Stress , Diabetic Nephropathies , Ellipticines , Inflammation , Antioxidants
6.
J. Health Biol. Sci. (Online) ; 10(1): 1-5, 01/jan./2022.
Article in English | LILACS | ID: biblio-1411471

ABSTRACT

Objectives: the aim of this study was to evaluate the effects of the association of dry extracts of Astragalus membranaceus, Peumus boldus and Curcuma longa in rats with induced diabetes. Methods: After the induction of type 2 diabetes by intraperitoneal streptozotocin, male Wistar rats were randomly assigned to groups (n=6) and treated for 20 days. The extracts were suspended in water and administered through orogastric gavage once daily as described: Group I: healthy control (saline); group II: received Astragalus membranaceus, Peumus boldus and Curcuma longa (400 mg/kg/day of each dry extract); group III: received Astragalus membranaceus, Peumus boldus, Curcuma longa (400 mg/kg/day of each dry extract) and glibenclamide (15 mg/kg/day). Fasting glucose, glucose tolerance, alanine aminotransferase, aspartate aminotransferase and fructosamine were evaluated. Results: Fasting blood glucose and glucose tolerance for groups II and III were influenced by treatments (p<0.05). The extracts did not significantly influence the efficacy of glibenclamide. Conclusion: The results found in this study allow us to consider that it is not possible to conclude that the compounds evaluated are not effective in DM in rats, due to variables such as total treatment period, doses, size of pancreatic injury caused by streptozotocin, and diet profile may have influenced the results. The studied compounds have potential for application in diabetes and further studies should be carried out to adjust the treatment.


Objetivos: avaliar os efeitos da associação de extratos secos de Astragalus membranaceus, Peumus boldus e Curcuma longa em ratos com diabetes induzida. Métodos: Após a indução de diabetes tipo 2 (DM) por estreptozotocina intraperitoneal, ratos Wistar machos foram distribuídos aleatoriamente em grupos (n=6) e tratados por 20 dias. Os extratos foram suspensos em água e administrados por gavagem orogástrica uma vez ao dia conforme descrito: Grupo I: controle saudável (solução salina); grupo II: recebeu Astragalus membranaceus, Peumus boldus e Curcuma longa (400 mg/kg/dia de cada extrato seco); grupo III: receberam Astragalus membranaceus, Peumus boldus, Curcuma longa (400 mg/kg/dia de cada extrato seco) e glibenclamida (15 mg/kg/dia). A glicemia de jejum, tolerância à glicose, alanina aminotransferase, aspartato aminotransferase e frutosamina foram avaliados. Resultados: A glicemia de jejum e a tolerância à glicose para os grupos II e III foram influenciadas pelos tratamentos (p<0,05). Os extratos não influenciaram significativamente na eficácia da glibenclamida. Conclusão: Os resultados encontrados neste estudo permitem considerar que não é possível concluir que os compostos avaliados não são eficazes no DM em ratos, devido às variáveis como tempo total de tratamento, doses e tamanho da lesão pancreática causada por estreptozotocina, além do perfil da dieta, que podem ter influenciado os resultados. Os compostos estudados têm potencial para aplicação em diabetes e mais estudos devem ser realizados para adequar o tratamento.


Subject(s)
Astragalus propinquus , Blood Glucose , Streptozocin , Fructosamine , Curcuma , Peumus , Diabetes Mellitus , Alanine Transaminase
7.
Journal of Southern Medical University ; (12): 463-472, 2022.
Article in Chinese | WPRIM | ID: wpr-936338

ABSTRACT

OBJECTIVE@#To investigate the effects of wogonoside on high glucose-induced dysfunction of human retinal microvascular endothelial cells (hRMECs) and streptozotocin (STZ)-induced diabetic retinopathy in rats and explore the underlying molecular mechanism.@*METHODS@#HRMECs in routine culture were treated with 25 mmol/L mannitol or exposed to high glucose (30 mmol/L glucose) and treatment with 10, 20, 30, 40 μmol/L wogonoside. CCK-8 assay and Transwell assay were used to examine cell proliferation and migration, and the changes in tube formation and monolayer cell membrane permeability were tested. ROS, NO and GSH-ST kits were used to evaluate oxidative stress levels in the cells. The expressions of IL-1β and IL-6 in the cells were examined with qRT-PCR and ELISA, and the protein expressions of VEGF, HIF-1α and SIRT1 were detected using Western blotting. We also tested the effect of wogonoside on retinal injury and expressions of HIF-1α, ROS, VEGF, TNF-α, IL-1β, IL-6 and SIRT1 proteins in rat models of STZ-induced diabetic retinopathy.@*RESULTS@#High glucose exposure caused abnormal proliferation and migration, promoted angiogenesis, increased membrane permeability (P < 0.05), and induced inflammation and oxidative stress in hRMECs (P < 0.05). Wogonoside treatment concentration-dependently inhibited high glucose-induced changes in hRMECs. High glucose exposure significantly lowered the expression of SIRT1 in hRMECs, which was partially reversed by wogonoside (30 μmol/L) treatment; interference of SIRT1 obviously attenuated the inhibitory effects of wogonoside against high glucose-induced changes in proliferation, migration, angiogenesis, membrane permeability, inflammation and oxidative stress in hRMECs. In rat models of STZ-induced diabetic retinopathy, wogonoside effectively suppressed retinal thickening (P < 0.05), alleviated STZ-induced retinal injury, and increased the expression of SIRT1 in the retinal tissues (P < 0.001).@*CONCLUSION@#Wogonoside alleviates retinal damage caused by diabetic retinopathy by up-regulating SIRT1 expression.


Subject(s)
Animals , Rats , Diabetes Mellitus/metabolism , Diabetic Retinopathy/metabolism , Endothelial Cells , Flavanones , Glucose/pharmacology , Glucosides , Inflammation/metabolism , Interleukin-6/metabolism , Neovascularization, Pathologic/metabolism , Reactive Oxygen Species/metabolism , Sirtuin 1/metabolism , Streptozocin/pharmacology , Vascular Endothelial Growth Factor A/metabolism
8.
China Journal of Chinese Materia Medica ; (24): 2533-2540, 2022.
Article in Chinese | WPRIM | ID: wpr-928133

ABSTRACT

Neuropathic pain is one of the common complications of diabetes. Tetrahydropalmatine(THP) is a main active component of Corydalis Rhizoma with excellent anti-inflammatory and pain-alleviating properties. This study aims to investigate the therapeutic effect of THP on diabetic neuropathic pain(DNP) and the underlying mechanism. High-fat and high-sugar diet(4 weeks) and streptozotocin(STZ, 35 mg·kg~(-1), single intraperitoneal injection) were employed to induce type-2 DNP in rats. Moreover, lipopolysaccharide(LPS) was used to induce the activation of BV2 microglia in vitro to establish an inflammatory cellular model. Fasting blood glucose(FBG) was measured by a blood glucose meter. Mechanical withdrawal threshold(MWT) was assessed with von Frey filaments, and thermal withdrawal latency(TWL) with hot plate apparatus. The protein expression levels of OX42, inducible nitric oxide synthase(iNOS), CD206, p38, and p-p38 were determined by Western blot, the fluorescence expression levels of OX42 and p-p38 in the dorsal horn of the rat spinal cord by immunofluorescence, the mRNA content of p38 and OX42 in rat spinal cord tissue by qRT-PCR, and levels of nitric oxide(NO), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and serum fasting insulin(FINS) by enzyme-linked immunosorbent assay(ELISA). RESULTS:: showed that the mo-del group demonstrated significant decrease in MWT and TWL, with pain symptoms. THP significantly improved the MWT and TWL of DNP rats, inhibited the activation of microglia and p38 MAPK signaling pathway in rat spinal cord, and ameliorated its inflammatory response. Meanwhile, THP promoted the change of LPS-induced BV2 microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, suppressed the activation of the p38 MAPK signaling pathway, decreased the expression levels of inflammatory factors NO, IL-1β, IL-6, and TNF-α, and increased the expression level of anti-inflammatory factor IL-10. The findings suggested that THP can significantly ameliorate the pain symptoms of DNP rats possibly by inhibiting the inflammatory response caused by M1 polarization of microglia via the p38 MAPK pathway.


Subject(s)
Animals , Rats , Berberine Alkaloids , Blood Glucose/metabolism , Diabetes Mellitus , Diabetic Neuropathies/genetics , Interleukin-10 , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Microglia , Neuralgia/metabolism , Rats, Sprague-Dawley , Signal Transduction , Spinal Cord/metabolism , Streptozocin/therapeutic use , Tumor Necrosis Factor-alpha/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
9.
Rev. cuba. invest. bioméd ; 40(3)sept. 2021. ilus, tab
Article in Spanish | LILACS, CUMED | ID: biblio-1408553

ABSTRACT

Introducción: Debido a sus propiedades químicas, la estreptozotocina es uno de los agentes diabetogénicos más utilizados para generar modelos biológicos de diabetes, por lo que es necesario estudiar cuáles son sus efectos en el organismo del animal de laboratorio. Objetivo: Evaluar, en un periodo de 90 días, los efectos de la inyección neonatal de estreptozotocina en ratas Wistar sobre indicadores bioquímicos y de estrés oxidativo en hígado y riñón. Métodos: La diabetes fue inducida neonatalmente por 100 mg de estreptozotocina en ratas Wistar. Se realizaron determinaciones de glucemia, insulina e indicadores de estrés oxidativos en hígado y riñón en cinco animales por grupo a los días 5, 10, 20, 30, 60, 90 de nacidos. Resultados: En todas las intervenciones, la glucemia e insulina mostraron diferencias significativas en el grupo-STZ respecto al control. El valor máximo de hiperglucemia se observó al quinto día. La concentración de nitratos y nitritos en hígado fue mayor que en riñón. En comparación con el grupo control, en el tejido hepático del grupo-STZ la concentración de nitratos y nitritos resultó significativamente superior los días 10-20. En todas las intervenciones se detectó consumo de glutatión reducido en ambos órganos. En el hígado de las ratas STZ no se demostró daño a lípidos ni proteínas; sin embargo, en riñón se detectó daño significativo en ambas biomoléculas al quinto día. Conclusiones: Tanto la citotoxicidad de la estreptozotocina neonatal como las concentraciones de glucosa e insulina inducidas repercutieron negativamente sobre los indicadores de estrés oxidativo estudiados en tejido hepático y renal(AU)


Introduction: Streptozotocin is currently one of the most used diabetogenic agents to generate biological models of diabetes due to its chemical properties, so it is necessary to study the consequences of STZ for the organism of the laboratory animal. Objective: To evaluate in a period of 90 days the effects of neonatal injection of streptozotocin in Wistar rats on biochemical indicators and oxidative stress in liver and kidney. Methods: Diabetes was induced neonatally by 100 mg of streptozotocin in Wistar rats. Blood glucose, insulin and oxidative stress indicators in liver and kidney were determined in 5 animals per group at days 5, 10, 20, 30, 60, 90 of birth. Results: Blood glucose and insulin showed significant differences in the STZ-group respect to the control group in all interventions. The maximum value of hyperglycemia was observed on day-5. The concentration of nitrates and nitrites in liver was higher than in kidney. In liver tissue of the STZ-group, this indicator was significantly higher on days 10-20 compared to the control. In all interventions, reduced glutathione consumption was demonstrated in the STZ-group compared to control in both organs. In the liver of STZ rats no lipid or protein damage was demonstrated. However, in the kidney, significant damage in both biomolecules was detected in the STZ-group on day-5. Conclusions: Neonatal streptozotocin cytotoxicity as well as induced glucose and insulin concentrations had a negative impact on oxidative stress indicators studied in liver and kidney tissue(AU)


Subject(s)
Animals , Rats , Rats, Wistar , Streptozocin/administration & dosage , Diabetes Mellitus, Experimental/chemically induced , Kidney , Liver , Animals, Laboratory
10.
Electron. j. biotechnol ; 53: 87-94, Sep.2021. graf, ilus, tab
Article in English | LILACS | ID: biblio-1451559

ABSTRACT

BACKGROUND Diabetes is a metabolic disorder caused by defects in insulin production and activity. During disease progression, changes in lipid peroxidation cause structural modifications via production of free radicals. Fangchinoline is a well-known alkaloid present in Stephaniae tetrandrine S. Moore, which has demonstrated antioxidant, anticancer, and anti-inflammatory activities. RESULTS The present study analyzed the anti-diabetic and antioxidant effects of fangchinoline in male rats with streptozotocin-induced diabetes. Rats were divided into the following groups: normal control, diabetic, diabetic + fangchinoline 100 mg/kg, diabetic + fangchinoline 200 mg/kg and diabetic + glibencla mide 600 mg/kg. The treatment was administered orally for 45 consecutive days. Lipid peroxidation was substantially increased by >50% in the serum, as well as the liver, kidney, and heart tissues of diabetic rats. However, fangchinoline supplementation significantly reduced lipid peroxidation to near normal levels. Reactive oxygen species levels were substantially increased by >500% in the serum, as well as the liver, kidney, and heart tissues of diabetic rats. Fangchinoline supplementation reduced reactive oxygen species to near normal levels. Fangchinoline supplementation significantly improved superoxide dismutase, glutathione peroxidase, catalase, and reduced glutathione levels in diabetic rats. Total hexoses, sialic acid, hexosamines, and fucose were increased in diabetic rats, whereas fangchinoline supplementation significantly reduced these total hexoses, sialic acid, hexosamines, and fucose to near normal levels CONCLUSIONS Supplementation with fangchinoline led to significant attenuation of the levels of lipid peroxidation, ROS, and glycoprotein components such as total hexoses, hexosamines, sialic acid, and fucose, while improving antioxidant marker levels


Subject(s)
Animals , Male , Rats , Benzylisoquinolines/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Reactive Oxygen Species , Streptozocin
11.
Bol. latinoam. Caribe plantas med. aromát ; 20(3): 303-314, may. 2021. tab, ilus
Article in English | LILACS | ID: biblio-1343478

ABSTRACT

In this study, against streptozotocin (STZ) induced diapetic nephropathy (DN); it is aimed to investigate the use of thymoquinone (TQ) and ß-aminoisobutyric acid (BAIBA) and to compare the effects of these agents. With random selection of 35 male rats, five groups (seven rats in each group) were constituted as follows: Control, STZ, STZ + TQ, STZ + BAIBA, STZ + TQ + BAIBA. In the STZ group; body weight, glutathione (GSH) and insulin levels decreased, relative kidney weight, malondialdehyde (MDA), glucose, blood urea nitrogen (BUN) and creatinine (Cr) levels were increased. Also, in kidney tissue; histopathological changes (such as thickening of the capsular, glomerular and tubular basement membranes, increased mesangial matrix amount, increased cytoplasmic vacuolization in some of the tubular epithelial cells, increased tumor necrosis factor-alpha (TNF-α) expression, and inflammatory cell infiltrations in interstitial tissue) were detected. It was observed that these changes occurring after diabetes mellitus (DM) reversed significantly in TQ, BAIBA and TQ + BAIBA groups.


En este estudio, contra la nefropatía diapética (ND) inducida por estreptozotocina (STZ); tiene como objetivo investigar el uso de timoquinona (TQ) y ácido ß-aminoisobutírico (BAIBA) y comparar los efectos de estos agentes. Con la selección aleatoria de 35 ratas macho, se constituyeron cinco grupos (siete ratas en cada grupo) como sigue: Control, STZ, STZ + TQ, STZ + BAIBA, STZ + TQ + BAIBA. En el grupo STZ; el peso corporal, los niveles de glutatión (GSH) y de insulina disminuyeron, el peso relativo de los riñones, el malondialdehído (MDA), la glucosa, el nitrógeno ureico en sangre (BUN) y los niveles de creatinina (Cr) aumentaron. Además, en tejido renal; se detectaron cambios histopatológicos (como engrosamiento de las membranas basales capsular, glomerular y tubular, aumento de la cantidad de matriz mesangial, aumento de la vacuolización citoplasmática en algunas de las células epiteliales tubulares, aumento de la expresión del factor de necrosis tumoral alfa (TNF-α) e infiltraciones de células inflamatorias en tejido intersticial). Se observó que estos cambios que ocurren después de la diabetes mellitus (DM) se revirtieron significativamente en los grupos TQ, BAIBA y TQ + BAIBA.


Subject(s)
Animals , Male , Rats , Benzoquinones/administration & dosage , Diabetic Nephropathies/drug therapy , Aminoisobutyric Acids/administration & dosage , Blood Urea Nitrogen , Body Weight , Immunohistochemistry , Rats, Sprague-Dawley , Streptozocin , Oxidative Stress , Creatinine/analysis , Disease Models, Animal , Glucose/analysis , Glutathione/analysis , Kidney/drug effects
12.
Braz. j. med. biol. res ; 54(11): e11352, 2021. tab, graf
Article in English | LILACS | ID: biblio-1339450

ABSTRACT

Diabetes mellitus is associated with neural and micro- and macrovascular complications. Therapeutic options for these complications are limited and the delivery of mesenchymal stem cells into lesions have been reported to improve the healing process. In this work, the effects of the administration of a lineage of human bone marrow mesenchymal stem cells immortalized by the expression of telomerase (hBMSC-TERT) as a potential therapeutic tool for wound healing in diabetic rats were investigated. This is the first description of the use of these cells in diabetic wounds. Dorsal cutaneous lesions were made in streptozotocin-induced diabetic rats and hBMSC-TERT were subcutaneously administered around the lesions. The healing process was evaluated macroscopically, histologically, and by birefringence analysis. Diabetic wounded rats infused with hBMSC-TERT (DM-TERT group) and the non-diabetic wounded rats not infused with hBMSC-TERT (CW group) had very similar patterns of fibroblastic response and collagen proliferation indicating improvement of wound healing. The result obtained by birefringence analysis was in accordance with that obtained by the histological analysis. The results indicated that local administration of hBMSC-TERT in diabetic wounds improved the wound healing process and may become a therapeutic option for wounds in individuals with diabetes.


Subject(s)
Humans , Animals , Rats , Telomerase , Diabetes Mellitus, Experimental , Mesenchymal Stem Cells , Wound Healing , Streptozocin
13.
Clinics ; 76: e3002, 2021. tab, graf
Article in English | LILACS | ID: biblio-1345816

ABSTRACT

OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is an important clinical problem that can be aggravated by diabetes mellitus, a major risk factor. However, heme oxygenase-1 (HO-1), a promising therapeutic target, can exert antioxidant effects against CI-AKI. Thus, we investigated the role of HO-1 in CI-AKI in the presence of diabetes mellitus. METHODS: Twenty-eight male Wistar rats weighing 250-300g were subjected to left uninephrectomy, and concomitantly, diabetes induced by streptozotocin (65 mg/kg). After 12 weeks, iodinated contrast (meglumine ioxithalamate, 6 mL/kg) and hemin (HO-1 inducer-10 mg/k) were administered 60 min before iodinated contrast treatment. The rats were randomly divided into four groups: control, diabetes mellitus (DM), DM iodinated contrast (DMIC), and DMIC hemin (DMICH). Kidney function, albuminuria, oxidative profile, and histology were assessed. All experimental data were subjected to statistical analyses. RESULTS: CI-AKI in preclinical diabetic models decreased creatinine clearance and increased urinary neutrophil gelatinase-associated lipocalin (NGAL) levels and the degree of albuminuria. Additionally, the levels of oxidative and nitrosative stress metabolites (urinary peroxides, thiobarbituric acid-reactive substances, and NO) were elevated, while thiol levels in kidney tissue were reduced. Kidney histology showed tubular cell vacuolization and edema. HO-1 inducer treatment improved kidney function and reduced urinary the NGAL levels. The oxidative profile showed an increase in the endogenous thiol-based antioxidant levels. Additionally, the tubular injury score was reduced following HO-1 treatment. CONCLUSIONS: Our findings highlight the renoprotective effects of HO-1 in CI-AKI and preclinical diabetic models. Therefore, HO-1 ameliorates kidney dysfunction, reduces oxidative stress, and prevents cell necrosis.


Subject(s)
Animals , Male , Rats , Diabetes Mellitus , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Rats, Wistar , Streptozocin/metabolism , Oxidative Stress , Heme Oxygenase-1/metabolism , Heme Oxygenase (Decyclizing)/metabolism , Kidney/metabolism
14.
Bol. latinoam. Caribe plantas med. aromát ; 20(2): 132-146, 2021. ilus, tab
Article in English | LILACS | ID: biblio-1342208

ABSTRACT

We investigated the effects of dichloromethane extract (DME) from Myrcia splendenson alterations caused by type 2 diabetes in the blood and kidney of rats, in order to reduce side effects caused by synthetic drugs. Rats received streptozotocin (60 mg/kg),15 minutes after nicotinamide (120 mg/kg) or water. After 72 hours, the glycemic levels were evaluated to confirm diabetes and the animals received (15 days) DME (25, 50, 100 or 150 mg/Kg) or water. DME partially reversed hyperglycemia and (100 and 150 mg/kg) reversed hypertriglyceridemia. Histopathological findings elucidated that DME reduced damage to pancreatic islets. DME 150 mg/kgreversed the increases in TBA-RS, the reduction in the sulfhydryl content, 100 and 150 mg/kg increased CAT, reversed the decrease in GSH-Px and increased it activity in the blood. DME 150 mg/kg reversed CAT and GSH-Px reductions in the kidney. We believe that DME effects might be dependent on the presence of phenolic compounds.


Investigamos los efectos del extracto de diclorometano (DME)de Myrcia splendens sobre las alteraciones causadas por la diabetes tipo 2 en la sangre y los riñones de las ratas, para reducir los efectos secundarios causados por las drogas sintéticas. Las ratas recibieron estreptozotocina (60 mg/kg), 15 minutos después de la nicotinamida (120 mg/kg) o agua. Después de 72 horas, se confirmo la diabetes y los animales recibieron (15 días) DME (25, 50, 100 o 150 mg/Kg) o agua. DME revierte parcialmente la hiperglucemia y revierte la hipertrigliceridemia. DME redujo el daño a los islotes pancreáticos. DME revirtió los aumentos en TBA-RS, la reducción en el contenido de sulfhidrilo, aumentó la CAT, revirtió la disminución en GSH-Px y aumentó su actividad en la sangre. Además, DME revirtió las reducciones de CAT y GSH-Px en el riñón. Creemos que los efectos provocados por DME pueden depender de la presencia de compuestos fenólicos.


Subject(s)
Animals , Male , Rats , Plant Extracts/administration & dosage , Myrtaceae/chemistry , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/administration & dosage , Methylene Chloride/administration & dosage , Blood Glucose/drug effects , Plant Extracts/chemistry , Chromatography, High Pressure Liquid , Rats, Wistar , Streptozocin , Oxidative Stress/drug effects , Spectrometry, Mass, Electrospray Ionization , Phenolic Compounds/analysis , Hypolipidemic Agents/administration & dosage , Antioxidants/administration & dosage
15.
Environmental Health and Preventive Medicine ; : 38-38, 2021.
Article in English | WPRIM | ID: wpr-880354

ABSTRACT

BACKGROUND@#Periploca aphylla is used by local population and indigenous medicine practitioners as stomachic, tonic, antitumor, antiulcer, and for treatment of inflammatory disorders. The aim of this study was to evaluate antidiabetic effect of the extract of P. aphylla and to investigate antioxidant and hypolipidemic activity in streptozotocin (STZ)-induced diabetic rats.@*METHODS@#The present research was conducted to evaluate the antihyperglycemic potential of methanol extract of P. aphylla (PAM) and subfractions n-hexane (PAH), chloroform (PAC), ethyl acetate (PAE), n-butanol (PAB), and aqueous (PAA) in glucose-overloaded hyperglycemic Sprague-Dawley rats. Based on the efficacy, PAB (200 mg/kg and 400 mg/kg) was tested for its antidiabetic activity in STZ-induced diabetic rats. Diabetes was induced via intraperitoneal injection of STZ (55 mg/kg) in rat. Blood glucose values were taken weekly. HPLC-DAD analysis of PAB was carried out for the presence of various polyphenols.@*RESULTS@#HPLC-DAD analysis of PAB recorded the presence of rutin, catechin, caffeic acid, and myricetin. Oral administration of PAB at doses of 200 and 400 mg/kg for 21 days significantly restored (P < 0.01) body weight (%) and relative liver and relative kidney weight of diabetic rats. Diabetic control rats showed significant elevation (P < 0.01) of AST, ALT, ALP, LDH, total cholesterol, triglycerides, LDL, creatinine, total bilirubin, and BUN while reduced (P < 0.01) level of glucose, total protein, albumin, insulin, and HDL in serum. Count of blood cells and hematological parameters were altered in diabetic rats. Further, glutathione peroxidase, catalase, superoxide dismutase, glutathione reductase, and total soluble protein concentration decreased while concentration of thiobarbituric acid reactive substances and percent DNA damages increased (P < 0.01) in liver and renal tissues of diabetic rats. Histopathological damage scores increased in liver and kidney tissues of diabetic rats. Intake of PAB (400 mg/kg) resulted in significant improvement (P < 0.01) of above parameters, and results were comparable to that of standard drug glibenclamide.@*CONCLUSION@#The result suggests the antihyperglycemic, antioxidant, and anti-inflammatory activities of PAB treatment in STZ-compelled diabetic rat. PAB might be used as new therapeutic agent in diabetic patients to manage diabetes and decrease the complications.


Subject(s)
Animals , Male , Rats , 1-Butanol/chemistry , Administration, Oral , Diabetes Mellitus, Experimental/drug therapy , Dose-Response Relationship, Drug , Hypoglycemic Agents/chemistry , Periploca/chemistry , Phytochemicals/chemistry , Plant Extracts/chemistry , Rats, Sprague-Dawley , Streptozocin/adverse effects
16.
Acta cir. bras ; 36(7): e360702, 2021. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1284915

ABSTRACT

ABSTRACT Purpose To develop a model of induction of type-2 diabetes (DM2) by combining low doses of streptozotocin (STZ) and a cafeteria diet. Methods Forty male Wistar rats (200 g) were allocated into four groups: control (non-diabetic, n = 10); STZ 30 mg/kg (diabetic, n = 10); STZ 35 mg/kg (diabetic,n = 10); and STZ 40 mg/kg (diabetic, n = 10). DM2 was induced with a single intraperitoneal injection of STZ after four weeks of cafeteria diet in the three diabetic groups. All animals were evaluated as for anthropometric, and biochemical analyses, as well as liver, kidney and pancreas histological analyses. Results Lower weight gain, higher water intake, higher Lee index, hyperglycemia and modified total protein, urea, alpha-amylase, as well as insulin resistance, hepatic steatosis, pancreas, and kidney injury were observed in animals treated with 35 and 40 mg/kg of STZ. Conclusions The results show that the experimental model using cafeteria diet associated with 35 mg/kg of STZ is a low-cost model and efficient in order to develop DM2, confirmed by the presence of polydipsia, hyperglycemia, altered biochemical tests, insulin resistance and damages to the liver, pancreas and kidney, which is similar to the disease found in humans.


Subject(s)
Animals , Male , Rats , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Type 2/etiology , Rats, Wistar , Streptozocin , Diet
17.
China Journal of Chinese Materia Medica ; (24): 5627-5640, 2021.
Article in Chinese | WPRIM | ID: wpr-921747

ABSTRACT

This study investigated the differential mechanisms of Rehmanniae Radix and Rehmanniae Radix Praeparata in improving diabetes in mice through AMPK-mediated NF-κB/NLRP3 signaling pathway. The diabetic mouse model was established with high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days), after which the mice were randomly divided into model group, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, catalpol group(250 mg·kg~(-1)), 5-hydroxymethylfurfural(5-HMF) group(250 mg·kg~(-1)), metformin group(250 mg·kg~(-1)), with the normal group also set. The organ indexes of heart,liver, spleen, lung, kidney and pancreas were calculated after four weeks of administration. The pathological changes and fibrosis of pancreas, kidney and liver in mice were observed by hematoxylin-eosin(HE) staining and Masson staining. Western blot was used to determine the expression levels of Toll-like receptor-4(TLR4), nuclear factor-κB(NF-κB), Nod-like receptor protein 3(NLRP3),interleukin-1β(IL-1β), adenosine monophosphate-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK) in the pancreas, kidney and liver of mice. Compared with the model group, the administration groups witnessed significant decrease in the liver,spleen, kidney, pancreas and fat indexes of diabetic mice, and there was no significant difference in heart and lung indexes. The pathological states and fibrosis of pancreatic, kidney and liver tissues were significantly improved after administration. Additionally, the expression levels of TLR4, NF-κB and NLRP3 in pancreas, kidney and liver of diabetic mice were significantly lowered. The expression levels of p-AMPK/AMPK were enhanced significantly in kidney and liver of mice in Rehmanniae Radix group while in pancreas, kidney and liver in Rehmanniae Radix Praeparata group. This suggests that Rehmanniae Radix and Rehmanniae Radix Praeparata differ in the mechanism of regulating energy metabolism of multiple organs and thereby exerting anti-inflammatory effects to alleviate symptoms of diabetic mice.


Subject(s)
Animals , Mice , AMP-Activated Protein Kinases/genetics , Diabetes Mellitus, Experimental/drug therapy , Diet, High-Fat/adverse effects , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Plant Extracts , Rehmannia , Signal Transduction , Streptozocin
18.
Braz. J. Pharm. Sci. (Online) ; 56: e18782, 2020. graf
Article in English | LILACS | ID: biblio-1249151

ABSTRACT

Cnidoscolus chayamansa is a native plant of the Mayan region, which is also cultivated in other places like northern Mexico, Tunisia and India. Many properties are attributed to Mayan Chaya, such as aid in the control of glycemia in diabetics. Thus this study aimed to evaluate the hypoglycemic effects of chaya aqueous extracts in a model of streptozotisin-induced diabetic Wistar rats. Chaya aqueous extracts were collected from plants cultivated in Quinta Roo (Mayan region) and Durango (northern Mexico), and in this study we compare their effect with metformin (as a control). Additionally, we compared the extracts mass profiles from both regions by high-resolution liquid chromatography coupled to a triple quadrupole tandem mass detector (HPLC-MS/MS QQQ). Finally, a study of the pancreatic tissue was carried out to evaluate the effects of the extracts on the Langerhans islets. Both extracts showed a good hypoglycemic effect after two weeks of treatment, and the Langerhans islets showed a partial recovery due to the effect of the treatment. Although the plants were cultivated at a distance of 2,350 km and under different weather, the compounds found in both did not show significant differences.


Subject(s)
Animals , Female , Rats , Plant Extracts/adverse effects , Streptozocin/administration & dosage , Euphorbiaceae/classification , Diabetes Mellitus/chemically induced , Hyperglycemia , Hypoglycemic Agents/adverse effects , Plants , Chromatography, High Pressure Liquid/methods , Islets of Langerhans
19.
Braz. J. Pharm. Sci. (Online) ; 56: e18772, 2020. tab, graf
Article in English | LILACS | ID: biblio-1285509

ABSTRACT

There is emerging evidence for a dysregulation of insulin signaling in the brains of patients with Alzheimer's disease (AD) with overlapping molecular features to Type 2 Diabetes Mellitus (T2DM). In addition, T2DM is a known risk factor of AD. The goal of this study was to investigate the neurogenic and neuroprotective potential of rosmarinic acid (RA) in a streptozotocin (STZ)-induced combined with high fat diet (HFD) mouse model of diabetes. Animals were divided into four experimental groups (control, diabetic, diabetic + RA, RA only). Behavioral analysis was performed to assess spatial learning and anxiety levels of animals, whereas quantitative real time PCR was carried out to assess the gene expression levels of neuronal markers of neurogenesis (Ki67, DCX and NeuN). A significant decrease in memory and spatial learning was observed in the diabetic mice, which was substantially improved by RA treatment. RA also increased the gene expression of NeuN, DCX and Ki67, which were dysregulated in the diabetic model. This study proposes RA as a potential therapeutic agent to mitigate neuronal dysfunction associated with T2DM by promoting adult hippocampal neurogenesis.


Subject(s)
Animals , Male , Mice , Diabetes Mellitus, Type 2/diagnosis , Alzheimer Disease/diagnosis , Risk Factors , Streptozocin/pharmacokinetics , Neurogenesis/genetics , Real-Time Polymerase Chain Reaction/methods
20.
Acta cir. bras ; 35(1): e202000106, 2020. graf
Article in English | LILACS | ID: biblio-1088526

ABSTRACT

Abstract Purpose To explore the role of all-trans retinoic acid (ATRA) in renal ischemia/reperfusion injury of diabetic rats. Methods Sixty adult male rats were randomly divided into 6 groups, including sham group (S group), ischemia-reperfusion group (I/R group), ischemia-reperfusion+ATRA group (A group), diabetic group (D group), diabetic ischemia-reperfusion group (DI/R group), diabetic ischemia-reperfusion +ATRA group (DA group). The levels of creatinine (Cr), cystatin C (Cys-C) and β2-microglobulin (β2-MG) were measured. Morphology of renal tissue was observed under light microscope. Results DJ-1, Nrf2, HO-1 and caspase-3 were detected by western blot. DJ-1, Nrf2, HO-1 and caspase-3 in I/R group, D group and DI/R group was higher than that in S group. Compared with I/R group, Nrf2 and HO-1 in A group was decreased, but caspase-3 was increased. However, Nrf2 in DA group was higher than that in DI/R group, HO-1 and caspase-3 in DA group were lower than that in DI/R group. Compared with group S, Cr, Cys-C and β2-MG in I/R group, A group, D group, and DI/R group were higher. Whereas the levels of Cr, Cys-C, β2-MG and renal injury score in DA group were lower than those in DI/R group. Conclusion ATRA has a protective effect on renal ischemia-reperfusion injury in diabetic rats, maybe relating to DJ/Nrf2 pathway.


Subject(s)
Animals , Male , Rats , Tretinoin/therapeutic use , Reperfusion Injury/prevention & control , Diabetes Mellitus, Experimental/chemically induced , NF-E2-Related Factor 2/therapeutic use , Kidney/drug effects , Tretinoin/pharmacology , Reperfusion Injury/pathology , Streptozocin , Disease Models, Animal , Drug Evaluation, Preclinical , NF-E2-Related Factor 2/pharmacology , Kidney/pathology
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