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Fulltext Perilla frutescens Leaf Extract and Fractions: Polyphenol Composition, Antioxidant, Enzymes (α-Glucosidase, Acetylcholinesterase, and Tyrosinase) Inhibitory, Anticancer, and Antidiabetic Activities

Wang Z, Tu Z, Xie X, Cui H, Kong KW, Zhang L

Foods, 2021 Feb 03;10(2).
PMID: 33546380 DOI: 10.3390/foods10020315

This study aims to evaluate the bioactive components, in vitro bioactivities, and in vivo hypoglycemic effect of P. frutescens leaf, which is a traditional medicine-food homology plant. P. frutescens methanol crude extract and its fractions (petroleum ether, chloroform, ethyl acetate, n-butanol fractions, and aqueous phase residue) were prepared by ultrasound-enzyme assisted extraction and liquid-liquid extraction. Among the samples, the ethyl acetate fraction possessed the high total phenolic (440.48 μg GAE/mg DE) and flavonoid content (455.22 μg RE/mg DE), the best antioxidant activity (the DPPH radical, ABTS radical, and superoxide anion scavenging activity, and ferric reducing antioxidant power were 1.71, 1.14, 2.40, 1.29, and 2.4 times higher than that of control Vc, respectively), the most powerful α-glucosidase inhibitory ability with the IC50 value of 190.03 μg/mL which was 2.2-folds higher than control acarbose, the strongest proliferative inhibitory ability against MCF-7 and HepG2 cell with the IC50 values of 37.92 and 13.43 μg/mL, which were considerable with control cisplatin, as well as certain inhibition abilities on acetylcholinesterase and tyrosinase. HPLC analysis showed that the luteolin, rosmarinic acid, rutin, and catechin were the dominant components of the ethyl acetate fraction. Animal experiments further demonstrated that the ethyl acetate fraction could significantly decrease the serum glucose level, food, and water intake of streptozotocin-induced diabetic SD rats, increase the body weight, modulate their serum levels of TC, TG, HDL-C, and LDL-C, improve the histopathology and glycogen accumulation in liver and intestinal tissue. Taken together, P. frutescens leaf exhibits excellent hypoglycemic activity in vitro and in vivo, and could be exploited as a source of natural antidiabetic agent.

Matched MeSH terms: Streptozocin
Fulltext Self-nanoemulsifying Delivery of Andrographolide: Ameliorating Islet Beta Cells and Inhibiting Adipocyte Differentiation

Syukri Y, Taher M, Martien R, Lukitaningsih E, Nugroho AE, Zakaria ZA

Adv Pharm Bull, 2021 Jan;11(1):171-180.
PMID: 33747864 DOI: 10.34172/apb.2021.018

Purpose:
Insulin resistance is a characteristic of non-insulin-dependent diabetes mellitus associated with obesity and caused by the failure of pancreatic beta cells to secrete sufficient amount of insulin. Andrographolide (AND) improves beta-cell reconstruction and inhibits fat-cell formation. This research aimed to improve the delivery of water-insoluble AND in self-nanoemulsifying (ASNE) formulation, tested in streptozotocin (STZ)-induced diabetic rats and 3T3-L1 preadipocyte cells.
Methods:
A conventional formulation of AND in suspension was used as a control. The experimental rats were orally administered with self-nanoemulsifying (SNE) and suspension of AND for 8 days. Measurements were performed to evaluate blood glucose levels in preprandial and postprandial conditions. Immunohistochemistry was used to assess the process of islet beta cell reconstruction. In vitro study was performed using cell viability and adipocyte differentiation assay to determine the delivery of AND in the formulation.
Results:
ASNE lowered blood glucose levels (day 4) faster than AND suspension (day 6). The histological testing showed that ASNE could regenerate pancreatic beta cells. Therefore, ASNE ameliorated pancreatic beta cells. The in vitro evaluation indicated the inhibition of adipocyte differentiation by both AND and ASNE, which occurred in a time-dependent manner. ASNE formulation had better delivery than AND.
Conclusion:
ASNE could improve the antidiabetic activity by lowering blood glucose levels, enhancing pancreatic beta cells, and inhibiting lipid formation in adipocyte cells.

Matched MeSH terms: Streptozocin
Fulltext Effect of Piper sarmentosum Extract on the Cardiovascular System of Diabetic Sprague-Dawley Rats: Electron Microscopic Study

Thent ZC, Seong Lin T, Das S, Zakaria Z

Evid Based Complement Alternat Med, 2012;2012:628750.
PMID: 23304208 DOI: 10.1155/2012/628750

Although Piper sarmentosum (PS) is known to possess the antidiabetic properties, its efficacy towards diabetic cardiovascular tissues is still obscured. The present study aimed to observe the electron microscopic changes on the cardiac tissue and proximal aorta of experimental rats treated with PS extract. Thirty-two male Sprague-Dawley rats were divided into four groups: untreated control group (C), PS-treated control group (CTx), untreated diabetic group (D), and PS-treated diabetic group (DTx). Intramuscular injection of streptozotocin (STZ, 50 mg/kg body weight) was given to induce diabetes. Following 28 days of diabetes induction, PS extract (0.125 g/kg body weight) was administered orally for 28 days. Body weight, fasting blood glucose, and urine glucose levels were measured at 4-week interval. At the end of the study, cardiac tissues and the aorta were viewed under transmission electron microscope (TEM). DTx group showed increase in body weight and decrease in fasting blood glucose and urine glucose level compared to the D group. Under TEM study, DTx group showed lesser ultrastructural degenerative changes in the cardiac tissues and the proximal aorta compared to the D group. The results indicate that PS restores ultrastructural integrity in the diabetic cardiovascular tissues.

Matched MeSH terms: Streptozocin
Fulltext The protective effect of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes

Mohamed J, Shing SW, Idris MH, Budin SB, Zainalabidin S

Clinics (Sao Paulo), 2013 Oct;68(10):1358-63.
PMID: 24212844 DOI: 10.6061/clinics/2013(10)11

OBJECTIVES: The aim of this study was to investigate the protective effects of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell (RBC) membrane oxidative stress in rats with streptozotocin-induced diabetes.
METHODS: Forty male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n = 10 rats each): control group (N), roselle-treated control group, diabetic group, and roselle-treated diabetic group. Roselle was administered by force-feeding with aqueous extracts of roselle (100 mg/kg body weight) for 28 days.
RESULTS: The results demonstrated that the malondialdehyde levels of the red blood cell membranes in the diabetic group were significantly higher than the levels in the roselle-treated control and roselle-treated diabetic groups. The protein carbonyl level was significantly higher in the roselle-treated diabetic group than in the roselle-treated control group but lower than that in the diabetic group. A significant increase in the red blood cell membrane superoxide dismutase enzyme was found in roselle-treated diabetic rats compared with roselle-treated control rats and diabetic rats. The total protein level of the red blood cell membrane, osmotic fragility, and red blood cell morphology were maintained.
CONCLUSION: The present study demonstrates that aqueous extracts of roselle possess a protective effect against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes. These data suggest that roselle can be used as a natural antioxidative supplement in the prevention of oxidative damage in diabetic patients.

Matched MeSH terms: Streptozocin
Fulltext Effect of the combination of gelam honey and ginger on oxidative stress and metabolic profile in streptozotocin-induced diabetic Sprague-Dawley rats

Sani NF, Belani LK, Sin CP, Rahman SN, Das S, Chi TZ, et al.

Biomed Res Int, 2014;2014:160695.
PMID: 24822178 DOI: 10.1155/2014/160695

Diabetic complications occur as a result of increased reactive oxygen species (ROS) due to long term hyperglycaemia. Honey and ginger have been shown to exhibit antioxidant activity which can scavenge ROS. The main aim of this study was to evaluate the antioxidant and antidiabetic effects of gelam honey, ginger, and their combination. Sprague-Dawley rats were divided into 2 major groups which consisted of diabetic and nondiabetic rats. Diabetes was induced with streptozotocin intramuscularly (55 mg/kg body weight). Each group was further divided into 4 smaller groups according to the supplements administered: distilled water, honey (2 g/kg body weight), ginger (60 mg/kg body weight), and honey + ginger. Body weight and glucose levels were recorded weekly, while blood from the orbital sinus was obtained after 3 weeks of supplementation for the estimation of metabolic profile: glucose, triglyceride (TG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH): oxidized glutathione (GSSG), and malondialdehyde (MDA). The combination of gelam honey and ginger did not show hypoglycaemic potential; however, the combination treatment reduced significantly (P < 0.05) SOD and CAT activities as well as MDA level, while GSH level and GSH/GSSG ratio were significantly elevated (P < 0.05) in STZ-induced diabetic rats compared to diabetic control rats.

Matched MeSH terms: Streptozocin
Altered cardiac tissue and plasma kininogen levels in hypertensive and diabetic rats

Sharma JN, Kesavarao U, Yusof AP

Immunopharmacology, 1999 Sep;43(2-3):129-32.
PMID: 10596843 DOI: 10.1016/s0162-3109(99)00070-3

The present investigation was aimed at evaluating the cardiac and total plasma kininogen levels, as well as LVWT in hypertensive and diabetic rats. STZ-induced diabetes produced a significant (P < 0.001) rise in mean arterial blood pressure (BP). The LVWT increased (P < 0.001) in SHR with and without diabetes) and diabetic WKYR. The cardiac tissue, as well as total plasma kininogen levels fell significantly (P < 0.001) in diabetic WKYR and SHR with and without diabetes compared to the control WKYR. These findings suggest that reduced kininogen levels may indicate a deficiency in kinin generation in the heart and in the peripheral circulation in diabetic and hypertensive rats. This effect may contribute to the development of LVH.

Matched MeSH terms: Streptozocin
Left ventricular hypertrophy and its relation to the cardiac kinin-forming system in hypertensive and diabetic rats

Sharma JN, Uma K, Yusof AP

Int J Cardiol, 1998 Feb 28;63(3):229-35.
PMID: 9578349 DOI: 10.1016/s0167-5273(97)00329-x

We investigated the cardiac tissue kallikrein and kininogen levels, left ventricular wall thickness and mean arterial blood pressure of Wistar Kyoto and spontaneously hypertensive rats with and without streptozotocin-induced diabetes. The mean arterial blood pressure was highly elevated (P<0.001) in Wistar Kyoto diabetic and spontaneously hypertensive diabetic rats as compared with their respective controls. The cardiac tissue kallikrein and kininogen levels were reduced significantly (P<0.001) in diabetic Wistar Kyoto, spontaneously hypertensive and diabetic spontaneously hypertensive compared with Wistar Kyoto control rats. In addition, the left ventricular thickness was found to be increased (P<0.001) in diabetic Wistar Kyoto and spontaneously hypertensive rats in the presence and in the absence of diabetes. Our results indicate that reduced activity of the kinin-forming system may be responsible for inducing left ventricular hypertrophy in the presence of raised mean arterial blood pressure in diabetic and hypertensive rats. Thus, the kinin-forming components might have a protective role against the development of left ventricular hypertrophy. The possible significance of these findings is discussed.

Matched MeSH terms: Streptozocin
Fulltext Evaluation of α-Glucosidase Inhibitory Effect of 50% Ethanolic Standardized Extract of Orthosiphon stamineus Benth in Normal and Streptozotocin-Induced Diabetic Rats

Mohamed EA, Ahmad M, Ang LF, Asmawi MZ, Yam MF

Evid Based Complement Alternat Med, 2015;2015:754931.
PMID: 26649063 DOI: 10.1155/2015/754931

In the present study, a 50% ethanolic extract of Orthosiphon stamineus was tested for its α-glucosidase inhibitory activity. In vivo assays of the extract (containing 1.02%, 3.76%, and 3.03% of 3'hydroxy-5,6,7,4'-tetramethoxyflavone, sinensetin, and eupatorin, resp.) showed that it possessed an inhibitory activity against α-glucosidase in normal rats loaded with starch and sucrose. The results showed that 1000 mg/kg of the 50% ethanolic extract of O. stamineus significantly (P < 0.05) decreased the plasma glucose levels of the experimental animals in a manner resembling the effect of acarbose. In streptozotocin-induced diabetic rats, only the group treated with 1000 mg/kg of the extract showed significantly (P < 0.05) lower plasma glucose levels after starch loading. Hence, α-glucosidase inhibition might be one of the mechanisms by which O. stamineus extract exerts its antidiabetic effect. Furthermore, our findings indicated that the 50% ethanolic extract of O. stamineus can be considered as a potential agent for the management of diabetes mellitus.

Matched MeSH terms: Streptozocin
Fulltext Effects of Canarium odontophyllum leaves on plasma glucose and T lymphocyte population in streptozotocin-induced diabetic rats

Saari SM, Basri DF, Budin SB, Warif NM

Saudi J Biol Sci, 2017 Feb;24(2):320-323.
PMID: 28149168 DOI: 10.1016/j.sjbs.2015.09.032

Type 1 diabetes mellitus is a chronic disease characterized by lack of insulin production. Immune mechanisms are implicated in the pathogenesis of Type 1 diabetes. Canarium odontophyllum (CO) fruits and leaves have been shown to possess high antioxidant activity. This study was conducted to evaluate the effects of CO leaves aqueous extract on the blood glucose and T lymphocyte population in the spleen of streptozotocin (STZ)-induced diabetic rats. Nineteen male Sprague-Dawley rats were randomly divided into three groups: normal, diabetic control and CO treated diabetic groups. Diabetes was induced by a single intraperitoneal injection of 65 mg STZ/kg body weight. The extract of CO leaves was administered orally by force feeding daily at the dose of 300 mg/kg for 28 days. The rats were sacrificed at the end of the study and the spleen was harvested for flow cytometry analysis. The results showed a significant decrease in body weight of diabetic and CO treated diabetic groups compared with the normal group (p

Matched MeSH terms: Streptozocin
Protective effect of daidzein against streptozotocin-induced Alzheimer's disease via improving cognitive dysfunction and oxidative stress in rat model

Wei J, Yang F, Gong C, Shi X, Wang G

J Biochem Mol Toxicol, 2019 Jun;33(6):e22319.
PMID: 30897277 DOI: 10.1002/jbt.22319

Oxidative stress is performing an essential role in developing Alzheimer's disease (AD), and age-related disorder and other neurodegenerative diseases. In existing research, we have aimed at investigating the daidzein (4',7-dihydroxyisoflavone) effect (10 and 20 mg/kg of body weight), as a free radical scavenger and antioxidant in streptozotocin (STZ) infused AD in rat model. Daidzein treatment led to significant improvement in intracerebroventricular-streptozotocin (ICV-STZ)-induced memory and learning impairments that was evaluated by Morris water maze test and spontaneous locomotor activity. It significantly restored the alterations in malondialdehyde, catalase, superoxide dismutase, and reduced glutathione levels. In addition, histopathological observations in cerebral cortex and hippocampal areas confirmed the neuroprotective effect of daidzein. These outcomes provide experimental proof showing preventive effect of daidzein on memory, learning dysfunction and oxidative stress in case of ICV-STZ rats. In conclusion, daidzein offers a potential treatment module for various neurodegenerative disorders with regard to mental deficits like AD.

Matched MeSH terms: Streptozocin
Fulltext Potential Effect of Polyphenolic-Rich Fractions of Corn Silk on Protecting Endothelial Cells against High Glucose Damage Using In Vitro and In Vivo Approaches

Hamzah N, Safuan S, Wan Ishak WR

Molecules, 2021 Jun 16;26(12).
PMID: 34208534 DOI: 10.3390/molecules26123665

Endothelial cell dysfunction is considered to be one of the major causes of vascular complications in diabetes. Polyphenols are known as potent antioxidants that can contribute to the prevention of diabetes. Corn silk has been reported to contain polyphenols and has been used in folk medicine in China for the treatment of diabetes. The present study aims to investigate the potential protective role of the phenolic-rich fraction of corn silk (PRF) against injuries to vascular endothelial cells under high glucose conditions in vitro and in vivo. The protective effect of PRF from high glucose toxicity was investigated using human umbilical vein endothelial cells (HUVECs). The protective effect of PRF was subsequently evaluated by using in vivo methods in streptozotocin (STZ)-induced diabetic rats. Results showed that the PRF significantly reduced the cytotoxicity of glucose by restoring cell viability in a dose-dependent manner. PRF was also able to prevent the histological changes in the aorta of STZ-induced diabetic rats. Results suggested that PRF might have a beneficial effect on diabetic patients and may help to prevent the development and progression of diabetic complications such as diabetic nephropathy and atherosclerosis.

Matched MeSH terms: Streptozocin/pharmacology
Carboxymethyl fenugreek galactomannan-gellan gum-calcium silicate composite beads for glimepiride delivery

Bera H, Mothe S, Maiti S, Vanga S

Int J Biol Macromol, 2018 Feb;107(Pt A):604-614.
PMID: 28916379 DOI: 10.1016/j.ijbiomac.2017.09.027

Novel carboxymethyl fenugreek galactomannan (CFG)-gellan gum (GG)-calcium silicate (CS) composite beads were developed for controlled glimepiride (GLI) delivery. CFG having degree of carboxymethylation of 0.71 was synthesized and characterized by FTIR, DSC and XRD analyses. Subsequently, GLI-loaded hybrids were accomplished by ionotropic gelation technique employing Ca+2/Zn+2/Al+3 ions as cross-linkers. All the formulations demonstrated excellent drug encapsulation efficiency (DEE, 48-97%) and sustained drug release behaviour (Q8h, 62-94%). These quality attributes were remarkably influenced by polymer-blend (GG:CFG) ratios, cross-linker types and CS inclusion. The drug release profile of the optimized formulation (F-6) was best fitted in zero-order model with anomalous diffusion driven mechanism. It also conferred excellent ex vivo mucoadhesive property and considerable hypoglycemic effect in streptozotocin-induced diabetic rats. Furthermore, the beads were characterized for drug-excipients compatibility, drug crystallinity, thermal behaviour and surface morphology. Thus, the developed hybrid matrices are appropriate for controlled delivery of GLI for Type 2 diabetes management.

Matched MeSH terms: Streptozocin
Metformin attenuated histopathological ocular deteriorations in a streptozotocin-induced hyperglycemic rat model

Nahar N, Mohamed S, Mustapha NM, Lau S, Ishak NIM, Umran NS

Naunyn Schmiedebergs Arch Pharmacol, 2021 Mar;394(3):457-467.
PMID: 33047165 DOI: 10.1007/s00210-020-01989-w

Diabetes mellitus (DM) often causes ocular disorders leading to vision loss. Metformin is commonly prescribed for type 2 diabetes. This study assessed the effect of metformin on hyperglycemic histopathological eye abnormalities and some possible pathways involved. Male rats were divided into 3 groups (N = 6), namely, healthy control, hyperglycemic non-treated control, and hyperglycemic rats treated with 200 mg/kg metformin. Two weeks after diabetes induction by an intraperitoneal streptozotocin (60 mg streptozotocin (STZ)/kg) injection, the rats develop ocular abnormalities, and metformin (200 mg/kg) treatment was administered daily. Rats underwent dilated retinal digital ophthalmoscope examination and graded for diabetic retinopathy. Rats were sacrificed at 12 weeks, and the cornea, lens, sclera, ciliary body, iris, conjunctiva, retinal, and optic nerve were examined histologically. Rats' fasting blood glucose and body weight were monitored. Serum tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), claudin-1, and glutathione/malondialdehyde ratios were analyzed. Metformin significantly attenuated diabetes-related histopathological ocular deteriorations in the cornea, lens, sclera, ciliary body, iris, conjunctiva, retina, and optic nerve partly by restoring serum TNF-α, VEGF, claudin-1, and glutathione/malondialdehyde ratios without significantly affecting the fasting blood glucose levels or body weight in these hyperglycemic rats. Metformin attenuated hyperglycemia-associated histopathological eye deteriorations, possibly partly by ameliorating vascular leakage, oxidative stress, inflammation, and neovascularization, without affecting the fasting blood glucose levels or body weights in these STZ-induced diabetic rats.

Matched MeSH terms: Streptozocin
Fulltext Gold nanoparticles attenuate albuminuria by inhibiting podocyte injury in a rat model of diabetic nephropathy

Alomari G, Al-Trad B, Hamdan S, Aljabali A, Al-Zoubi M, Bataineh N, et al.

Drug Deliv Transl Res, 2020 Feb;10(1):216-226.
PMID: 31637677 DOI: 10.1007/s13346-019-00675-6

Several recent studies have reported that gold nanoparticles (AuNPs) attenuate hyperglycemia in diabetic animal models without any observed side effects. The present study was intended to provide insight into the effects of 50-nm AuNPs on diabetic kidney disease. Adult male rats were divided into three groups (n = 7/group): control (non-diabetic, ND), diabetic (D), and diabetic treated intraperitoneally with 50-nm AuNPs (AuNPs + D; 2.5 mg/kg/day) for 7 weeks. Diabetes was induced by a single-dose injection of 55 mg/kg streptozotocin. The result showed that AuNP treatment prevented diabetes-associated increases in the blood glucose level. Reduction in 24-h urinary albumin excretion rate, glomerular basement membrane thickness, foot process width, and renal oxidative stress markers was also demonstrated in the AuNP-treated group. In addition, the results showed downregulation effect of AuNPs in renal mRNA or protein expression of transforming growth factor β1 (TGF-β1), fibronectin, collagen IV, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor-A (VEGF-A). Moreover, the protein expression of nephrin and podocin, podocyte markers, in glomeruli was increased in the AuNPs + D group compared with the D group. These results provide evidence that 50-nm AuNPs can ameliorate renal damage in experimental models of diabetic nephropathy through improving the renal function and downregulating extracellular matrix protein accumulation, along with inhibiting renal oxidative stress and amelioration of podocyte injury.

Matched MeSH terms: Streptozocin
Fulltext Alleviation of diabetic nephropathy by zinc oxide nanoparticles in streptozotocin-induced type 1 diabetes in rats

Alomari G, Al-Trad B, Hamdan S, Aljabali AAA, Al Zoubi MS, Al-Batanyeh K, et al.

IET Nanobiotechnol, 2021 Jul;15(5):473-483.
PMID: 34694755 DOI: 10.1049/nbt2.12026

This study examines the effect of nanoparticles with zinc oxides (ZnONPs) on diabetic nephropathy, which is the primary cause of mortality for diabetic patients with end-stage renal disease. Diabetes in adult male rats was induced via intraperitoneal injection of streptozotocin. ZnONPs were intraperitoneally administered to diabetic rats daily for 7 weeks. Diabetes was associated with increases in blood glucose level, 24-h urinary albumin excretion rate, glomerular basement membrane thickness, renal oxidative stress markers, and renal mRNA or protein expression of transforming growth factor-β1, fibronectin, collagen-IV, tumour necrosis factor-α and vascular endothelial growth factor-A. Moreover, the expression of nephrin and podocin, and the mRNA expression of matrix metalloproteinase-9 were decreased in the diabetic group. These changes were not detected in the control group and were significantly prevented by ZnONP treatment. These results provide evidence that ZnONPs ameliorate the renal damage induced in a diabetic rat model of nephropathy through improving renal functionality; inhibiting renal fibrosis, oxidative stress, inflammation and abnormal angiogenesis; and delaying the development of podocyte injury. The present findings may help design the clinical application of ZnONPs for protection against the development of diabetic nephropathy.

Matched MeSH terms: Streptozocin/toxicity
Piper sarmentosum water extract attenuates diabetic complications in streptozotocin induced sprague-dawley rats

FARIDA HUSSAN, NUR NAZILAH BT MAT ZIN, MOHD RAMDZI BIN ZULLKEFLI, YOW SC, NOOR ADIBAH BT ABDULLAH, TEOH SL

Sains Malaysiana, 2013;42:1605-1612.

Piper sarmentosum has been shown to possess antihyperglycemic effect. The effect of water extract of PS leaves was determined on the diabetic complications in streptozotocin induced rats. Eighteen male Sprague Dawley rats (n=18) were randomly divided into three groups with six rats each, namely, control, diabetic untreated and PS treated diabetic groups. Diabetes was induced with intramuscular injection of STZ (50 mg/kg). Ten days following the induction, the diabetes was confirmed with fasting blood sugar level more than 8 mmol/L and PS extract was administered orally (0.125 g/kg) for 28 days. The left kidneys were collected to analyze. The body weight and kidney weight index showed significant differences between control and diabetic groups (p<0.05). However, the lesser extent of body weight gain was observed in diabetic group compared with the control groups. The fasting blood sugar level was reduced in PS treated group. The percent area occupied by the glomerulus over a renal corpuscle was found to be 74.5% in DPS, 72% in DNT and 75% in C group; however it was statistically insignificant. Histological study revealed marked inflammatory cells infiltration and glomeruli contraction with widened urinary spaces revealed in DNT group following 28 days of hyperglycemic state whereas the DPS group showed features of improvement. The water extract of PS leaves has the potential preventive effect on the diabetic nephropathy by reducing hyperglycemia.

Matched MeSH terms: Streptozocin
Fulltext Protecting mechanism of Swietenia macrophylla ethanol extract nanoparticle on streptozotocin induced renal damage in rat

Kurnijasanti R, Wardani G, Mustafa MR, Sudjarwo SA

Open Vet J, 2023 Dec;13(12):1623-1630.
PMID: 38292712 DOI: 10.5455/OVJ.2023.v13.i12.12

BACKGROUND: Hyperglycemia increases reactive oxygen species (ROS), which contributes to diabetic complications such as kidney cell damage. Antioxidant administration could inhibit ROS and kidney cell damage commonly seen in hyperglycemia.
AIM: We want to demonstrate that the antioxidant properties of Swietenia macrophylla ethanol extract nanoparticles can prevent kidney cell damage brought on by streptozotocin (STZ) in the current investigation.
METHODS: This study employs high-energy ball milling to produce nanoparticles from S. macrophylla extract. Additionally, dynamic light scattering (DLS) is utilized to characterize the nanoparticle sizes of the S. macrophylla ethanol extract. Five groups, each consisting of 8 rats, were formed from 40 rats. Control rats received distilled water, the diabetic rats were administered STZ injections, while S. macrophylla rats were given S. macrophylla extract nanoparticles orally and STZ injection. After the trial, blood from a rat was drawn intracardially to check the levels of blood urea nitrogen (BUN) and creatinine. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were then assessed in kidney tissue samples. Histological alterations were evaluated in kidney section samples.
RESULTS: A DLS analysis estimated the size of the S. macrophylla ethanol extract nanoparticles to be about 91.50 ± 23.06 nm. BUN and creatinine levels were significantly raised after STZ treatment. STZ significantly decreased SOD and GPx levels in kidney tissue while raising MDA levels (p < 0.05). Swietenia macrophylla ethanol extract nanoparticle caused the decreased levels of BUN and creatinine in blood to normal levels (p < 0.05), indicating that S. macrophylla ethanol extract prevented the STZ-induced kidney cell damage. Additionally, S. macrophylla nanoparticles significantly raise GPx and SOD levels in kidney tissue while lowering MDA levels (p < 0.05). These actions are thought to have prevented kidney histological alterations (degeneration and necrosis) in diabetic rats.
CONCLUSION: According to these results, the anti-oxidative stress properties of S. macrophylla nanoparticles make them potentially effective nephroprotective therapies for STZ-induced kidney cell damage.

Matched MeSH terms: Streptozocin/pharmacology
Fulltext Structural changes in the urinary bladder of streptozotocin-induced diabetic rats and the possible protective role of insulin

Elnagar, Amir M. Bassam, Suhaidah Ibrahim, Abouelnaga, Mostafa A.M., Soliman, Amro Mohamed

International Medical Journal Malaysia, 2018;17(3):39-48.
MyJurnal

Introduction: Diabetes mellitus possesses severe adverse effects on the urinary bladder. Urinary bladder dysfunction is a common health problem affecting diabetic patients causing recurrent infections and urinary incontinence. Objective: To evaluate the histopathological changes in the tissue of urinary bladder in Streptozotocin (STZ) diabetic rats and the protective role of insulin. Methods: Thirty rats were classified into three groups: a control group which received no treatment (Group A), STZ diabetic group (Group B) and Insulin diabetic group (Group C). Animals were sacrificed after six weeks and urinary bladders were harvested and processed for light and electron microscopy. Results: Several histopathological changes were observed in the urinary bladder of the diabetic group including an increase in the thickness of the urothelium, epithelial cells with dark nuclei and large lenticular vesicles, and wide intercellular spaces with numerous collagen fibers. Treatment with insulin reduced the pathological changes induced by STZ. Conclusion: Diabetes mellitus caused significant pathological changes in the urinary bladder of experimental rats. For instance, treating diabetic animals with insulin prevented the development of damaging effects of diabetes on the urinary bladder.

Matched MeSH terms: Streptozocin
Effects of angiotensin 1-7 on the actions of angiotensin II in the renal and mesenteric vasculature of hypertensive and streptozotocin-induced diabetic rats

Dharmani M, Mustafa MR, Achike FI, Sim MK

Eur J Pharmacol, 2007 Apr 30;561(1-3):144-50.
PMID: 17320855

Angiotensin 1-7, a heptapeptide derived from metabolism of either angiotensin I or angiotensin II, is a biologically active peptide of the renin-angiotensin system. The present study investigated the effect of angiotensin 1-7 on the vasopressor action of angiotensin II in the renal and mesenteric vasculature of Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and streptozotocin-induced diabetic rats. Angiotensin II-induced dose-dependent vasoconstrictions in the renal vasculature. The pressor response was enhanced in the SHR and reduced in the streptozotocin-diabetic rat compared to WKY rats. Angiotensin 1-7 attenuated the angiotensin II pressor responses in the renal vasculature of WKY and SHR rats. However, the ability to reduce angiotensin II response was diminished in diabetic-induced rat kidneys. The effect of angiotensin 1-7 was not inhibited by 1-[(4-(Dimethylamino)-3-methylphenyl] methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate (PD123319), an angiotensin AT(2) receptor antagonist. (D-ALA(7))-Angiotensin I/II (1-7) (D-ALA) (an angiotensin 1-7 receptor antagonist), indomethacin (a cyclo-oxygenase inhibitor), and N(omega)-Nitro-L-Arginine Methyl Ester (L-NAME)(a nitric oxide synthetase inhibitor) abolished the attenuation by angiotensin 1-7 in both WKY rats and SHR, indicating that its action is mediated by angiotensin 1-7 receptor that is either coupled to the release of prostaglandins and/or nitric oxide. The vasopressor responses to angiotensin II in mesenteric vasculature bed was also dose-dependent but smaller in magnitude compared to the renal vasculature. The responses to angiotensin II were relatively smaller in SHR but no significant difference was observed between WKY and streptozotocin-induced diabetic rats. Angiotensin 1-7 attenuated the angiotensin II pressor responses in WKY, SHR and diabetic-induced mesenteric bed. The attenuation was observed at the lower concentrations of angiotensin II in WKY and diabetic-induced rats but at higher concentrations in SHR. Similar observation as in the renal vasculature was seen with PD123319, D-ALA, and L-NAME. Indomethacin reversed the attenuation by angiotensin 1-7 only in the SHR mesenteric vascular bed. The present findings support the regulatory role of angiotensin 1-7 in the renal and mesenteric vasculature, which is differentially altered in hypertension and diabetes.

Matched MeSH terms: Streptozocin
Fulltext Deferoxamine preconditioning to restore impaired HIF-1α-mediated angiogenic mechanisms in adipose-derived stem cells from STZ-induced type 1 diabetic rats

Mehrabani M, Najafi M, Kamarul T, Mansouri K, Iranpour M, Nematollahi MH, et al.

Cell Prolif, 2015 Oct;48(5):532-49.
PMID: 26332145 DOI: 10.1111/cpr.12209

OBJECTIVES: Both excessive and insufficient angiogenesis are associated with progression of diabetic complications, of which poor angiogenesis is an important feature. Currently, adipose-derived stem cells (ADSCs) are considered to be a promising source to aid therapeutic neovascularization. However, functionality of these cells is impaired by diabetes which can result from a defect in hypoxia-inducible factor-1 (HIF-1), a key mediator involved in neovascularization. In the current study, we sought to explore effectiveness of pharmacological priming with deferoxamine (DFO) as a hypoxia mimetic agent, to restore the compromised angiogenic pathway, with the aid of ADSCs derived from streptozotocin (STZ)-induced type 1 diabetic rats ('diabetic ADSCs').
MATERIALS AND METHODS: Diabetic ADSCs were treated with DFO and compared to normal and non-treated diabetic ADSCs for expression of HIF-1α, VEGF, FGF-2 and SDF-1, at mRNA and protein levels, using qRT-PCR, western blotting and ELISA assay. Activity of matrix metalloproteinases -2 and -9 were measured using a gelatin zymography assay. Angiogenic potential of conditioned media derived from normal, DFO-treated and non-treated diabetic ADSCs were determined by in vitro (in HUVECs) and in vivo experiments including scratch assay, three-dimensional tube formation testing and surgical wound healing models.
RESULTS: DFO remarkably enhanced expression of noted genes by mRNA and protein levels and restored activity of matrix metalloproteinases -2 and -9. Compromised angiogenic potential of conditioned medium derived from diabetic ADSCs was restored by DFO both in vitro and in vivo experiments.
CONCLUSION: DFO preconditioning restored neovascularization potential of ADSCs derived from diabetic rats by affecting the HIF-1α pathway.

Matched MeSH terms: Streptozocin/toxicity

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