Groups Of Diabetic Rats Research Articles

Mango (Mangifera indica L.) seed kernel extract suppresses hyperglycemia by modulating pancreatic β cell apoptosis and dysfunction and hepatic glucose metabolism in diabetic rats.

This study investigated the anti-hyperglycemic action of mango seed kernel extract (MKE) and various mechanisms involved in its actions to improve pancreatic β cells and hepatic carbohydrate metabolism in diabetic rats. An intraperitoneal injection of 60mg/kg of streptozotocin (STZ) followed by 30 consecutive days of treatment with MKE (250, 500, and 1000mg/kg body weight) was used to establish a study group of diabetic rats. Using liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) for identification, 26 chemical compounds were found in MKE and the high-performance liquid chromatography (HPLC) analysis of the MKE also revealed the existence of mangiferin, gallic acid, and quercetin. The results confirmed that in each diabetes-affected rat, MKE mitigated the heightened levels of fasting blood glucose, diabetic symptoms, glucose intolerance, total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C). As demonstrated by a remarkable increment in serum and pancreatic insulin, the diabetic pancreatic β cell function was potentiated by treating with MKE. The effect of MKE on diabetic pancreatic apoptosis clearly reduced the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells, which was related to diminished levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and Bax and an increase in Bcl-xL protein expression. Furthermore, diabetes-induced liver damage was clearly ameliorated along with a notable reduction in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and abnormal liver histology. By enhancing anti-oxidant superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, MKE alleviated diabetes-induced pancreatic and liver oxidative damage, as demonstrated by diminished levels of malondialdehyde. In minimizing the expression levels of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase-1 proteins in the diabetic liver, MKE also enhanced glycogen content and hexokinase activity. Collectively, these findings indicate that by suppressing oxidative and inflammatory processes, MKE exerts a potent anti-hyperglycemic activity in diabetic rats which serve to protect pancreatic β cell apoptosis, enhance their function, and improve hepatic glucose metabolism.

Effect of methanolic extract of Ventilago maderaspatana leaves on liver function markers and histopathology of liver tissue in streptozotocin-induced diabetic rats

Aim: The liver is particularly vulnerable to oxidative stress brought on by hyperglycemia since it is the main tissue. In order to better understand how Ventilago maderaspatana leaf methanolic extract (MEVML) affects liver function markers and the histology of liver tissue in STZ-induced diabetic rats, this study looked into the hepatoprotective potential of MEVML. Method: A single STZ dose of 50 mg/kg body weight was given to the animals to cause diabetes. All of the experimental groups' serum was tested for levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), and urea content. Results: The results revealed a marked increase in the serum levels of urea, ALT, AST, ALP, and GGT activity. The results of MEVML treatment, however, were equivalent to those of glibenclamide treatment in that they led to a decline in the activity of ALT, ALP, AST, GGT, and urea content in the diabetic group of rats. Furthermore, diabetic rats' liver tissue showed considerable histological alterations. However, treatment with Ventilago maderaspatana methanolic leaf extract and glibenclamide considerably reduced these histological alterations. Conclusion: Overall, the findings of our study show that MEVML reduces liver function biomarkers and restores the architecture of hepatic tissue to reduce hepatic tissue damage under diabetes stress conditions.

Safety and antidiabetic activity of Lagenaria siceraria (Molina) Standl. juice in streptozotocin -induced diabetic rats

Ethnopharmacological relevanceDiabetes and its complications have overwhelmed India's healthcare system. Current therapies are expensive and have adverse side effects, thus dietary changes and alternative treatments are needed. Lagenaria siceraria (Molina) Standl. Juice is used mainly for its nutritional and medicinal values, however toxicity of the juice and antidiabetic effects have been poorly characterized. Aim of the studyTo investigate the toxicity, anti-diabetic and anti-inflammatory efficacy of Lagenaria siceraria (Molina) Standl. (LS) juice. Materials and methodsIn vitro antidiabetic (α-glucosidase, α-amylase and DPP-4 inhibitory) activities were screened using standard procedures. The glucose uptake test was carried out by using L6 rat skeletal muscle cell line. In vivo sub-acute toxicity of LS juice was assessed on Wistar rats. Wistar rats were induced with diabetes by a single intraperitoneal (I.P) injection of freshly prepared streptozotocin (55 mg/kg body weight). The animals were randomly divided into 6 groups: normal control, untreated diabetic control, diabetic rats. Different dose of 200 mg/kg, 400 mg/kg and 600 mg/kg body weight of LS juice were administered, one group of diabetic rats were administered with 2 IU/mL insulin. The rats were sacrificed on the 31st day of the experiment and various in vivo biochemical parameters were evaluated in the serum and tissue homogenates of diabetic rats. ResultsSignificant dose-dependent inhibition of α-amylase (22.6%), α-glucosidase (50.13%), and DPP-4 (61.50%) activity was observed by LS juice. LS juice (10 μg/mL) increased insulin-mediated 2NBDG (2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) Amino)-2-Deoxyglucose) absorption in L6 cells. Animals treated with LS juice showed no toxicity or unfavorable pharmacological effects. Lagenaria siceraria (Molina) Standl. Juice improved glucose tolerance in diabetic rats with reduced fasting blood glucose. Lipopolysaccharide induced NF-κB, TNF-α and IL-1β production was also decreased in rats fed with LS juice. ConclusionLagenaria siceraria (Molina) Standl. Juice has demonstrated promising anti-inflammatory properties as well as the capacity to inhibit the digestion enzymes glucosidase and amylase. Our findings thus open new avenues for further research into the antidiabetic potential of LS juice.

Effects of SGLT2 inhibitor administration on blood glucose level and body weight in type 1 diabetes rat model.

The prevalence of diabetes worldwide is increasing and 629 million people are projected to have diabetes by 2045, and the most significant burden of the disease being concentrated in low- and middle-income countries (LMICs). Type 2 diabetes is mainly treated with insulin adjunctive therapies such as metformin to improve insulin sensitivity and sodium-glucose co-transporter 2 (SGLT2) inhibitors to lower blood glucose levels. However, there was limited study on the application of SGLT2 inhibitors on type 1 diabetes, particularly empagliflozin. Therefore, this study aimed to determine the effect of SGLT2 inhibitors on blood glucose levels and body weights in a rat model of type 1 diabetes. To mimic type 1 diabetes, the rats were injected with streptozotocin 60 mg intra-peritoneally. Twenty-four rat models were randomly divided into four groups: normal rat group (negative control), untreated diabetic rat group (positive control), type 1 diabetic rats treated with metformin, and type 1 diabetic rats treated with empagliflozin. Blood glucose levels and body weight were recorded before and after induced with streptozotocin and on weeks 4, 6, 8 and 10 of the treatment with anti-diabetic drugs. This study found that the blood glucose levels before and after treatment significantly decreased in all groups (p<0.05), except in the negative control group. Similar results were observed in body weight of the rats, which all groups experienced weight loss, except the negative control. These results suggested that apart from being used in type 2 diabetes, SGLT2 inhibitors may also be used as a treatment for type 1 diabetes.

DLBS3233 enhances nephrin and podocin expression also reduces oxidative stress marker and insulin receptor serine diabetic rats' podocytes.

Thirty adult male Wistar rats were randomly divided into six groups (n=5 per group): group of nondiabetic rats as a negative control (group 1); untreated diabetic rats (group 2); diabetic rats treated with DLBS3233 4.5mg/kg BB (group 3); 9mg/kg BB (group 4); 18mg/kg BB (group 5); and diabetic rats treated with pioglitazone (group 6). The authors checked Homeostatic Model Assessment for Insulin Resistance to corroborate insulin resistance prior to DLBS3233 administration in diabetic rats. Immunohistochemistry was performed to examine the expression of renal antimalondialdehyde (MDA) antibodies, nephrin, podocin, and insulin receptor serine. The data were analyzed using analysis of variance and the t-test. In the DBLS3233 group, immunohistochemistry showed enhanced expression of renal nephrin and podocin, as well as diminished expression of anti-MDA antibody, along with decreased insulin receptor serine. From statistical analysis, anti-MDA antibodies and insulin receptor serine showed lower expression, whereas the expression of nephrin and podocin were enhanced compared to untreated groups (P<0.05). DLBS3233 reduces oxidative stress by decreasing MDA and improves insulin resistance by increasing the expression of renal nephrin and podocin as well as decreasing insulin receptor serine.

Fortification of Fermented Camel Milk with Salvia officinalis L. or Mentha piperita Leaves Powder and Its Biological Effects on Diabetic Rats.

The incorporation of fermented camel milk with natural additives possesses numerous benefits for the treatment of various pathological and metabolic conditions. The present study investigated the impact of fortification of fermented camel milk with sage or mint leaves powder (1 and 1.5%, respectively) on glucose and insulin levels, lipid profile, and liver and kidney functions in alloxan-induced diabetic rats. The gross chemical composition of sage and peppermint leaves powder was studied. The chemical composition of sage and mint extracts was performed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS) of sage and mint extracts. Furthermore, a total of forty-two adult normal male albino rats were included in this study, whereas one group was kept as the healthy control group (n = 6 rats) and diabetes was induced in the remaining animals (n = 36 rats) using alloxan injection (150 mg/kg of body weight). Among diabetic rats groups, a control group (n = 6 rats) was kept as the diabetic control group whereas the other 5 groups (6 rats per group) of diabetic rats were fed fermented camel milk (FCM) or fermented camel milk fortified with 1 and 1.5% of sage or mint leaves powder. Interestingly, the oral administration of fermented camel milk fortified with sage or mint leaves powder, at both concentrations, caused a significant decrease in blood glucose level and lipid profile, and an increase in insulin level compared to the diabetic control and FCM groups. Among others, the best results were observed in the group of animals that received fermented camel milk fortified with 1.5% sage powder. In addition, the results revealed that the fermented camel milk fortified with sage or mint leaves powder improved the liver and kidney functions of diabetic rats. Our study concluded that the use of sage and mint leaves powder (at a ratio of 1.5%) with fermented camel milk produces functional food products with anti-diabetic activity.

Comparative impact of streptozotocin on altering normal glucose homeostasis in diabetic rats compared to normoglycemic rats

Diabetes mellitus is a syndrome and an endocrine disorder, primarily considered as a loss of glucose homeostasis because of the insulin action and/or secretion or both. Currently there are more than 150 million people in the world affected by diabetes mellitus with a higher share of Asian and European countries. The current study aimed to investigate the comparative altering properties of streptozotocin (STZ), based on up-turn and down-turn configuration of biochemical, toxicological and hematological parameters in comparison with normoglycemic male albino rats. This comparative study was conducted among normoglycemic and STZ based induced-type 2 diabetic male albino rats groups. The male albino rats were intra-peritoneally injected with STZ with the dose rate of 65 mg/kg body weight for one time to developed type 2 diabetic model. Biochemical (blood glucose, uric acid, urea and creatinine), toxicological (AST, ALT and ALP) and hematological parameters (red and white blood cells) and their functional indices were evaluated in type 2 diabetic induced group along with normoglycemic rats. The STZ based induced- type 2 diabetic rats showed statistically significance (p < 0.001) higher level in the blood glucose, alongwith the change in the levels of biochemical parameters including urea, uric acid, and creatinine. Toxicological parameters comprising AST, ALT and ALP were also shown significance (p < 0.001) as sufficient after experimental evaluation of biologically important parameter in STZ based induced-type 2 diabetic rats. Likewise, the red blood cells, white blood cells and their efficient components were exposed significantly insufficient after the injecting of STZ to induce the rats as type 2 diabetic. The results of the current study indicates the comparatively higher levels of variation among biochemical, toxicological and hematological parameters in STZ based Induced-type 2 diabetic model as compared to normoglycemic group.

Antidiabetic activity of methanol extract and fractions of Costus speciosus leaves in normal and alloxan induced diabetic rats

Introduction: Costus speciosus is a common plant used for the treatment of diabetes mellitus and various other ailments in traditional medicine in Sri Lanka. The present study was conducted to investigate the hypoglycemic effect of the leaves of C. speciosus in both normal and alloxan induced male Wistar diabetic rat models. Methods: A methanolic extract of the leaves was produced and used for the preliminary phytochemicals screening. Methanol extract was further partitioned with different solvents (n-hexane, chloroform, ethyl acetate and n-butanol) according to their polarity. Male Wistar rats weighing 150-220 g were randomly divided during the test. In vivo antidiabetic activity of partitioned fractions of C. speciosus leaves was performed in normal rats and alloxan induced NIDDM rats. Standard t-test was used to determine statistical significance. Results: A glucose tolerance test with normal rats indicated that peak levels of blood glucose were reached in 90 minutes after the glucose load. It is noteworthy that the test group recorded a significantly (p &lt; 0.05) lower blood glucose level at 90 minutes, indicating that the 80 % methanol extract exerted an overall hypoglycemic effect with normal rats at 90 minutes, despite being challenged with glucose load. The same dose showed an improvement in the glucose tolerance of alloxan-induced diabetic rats, reducing the blood glucose at 90 minutes by 60 % compared with control. These effects were found to be comparable with the effect of the synthetic drug glipizide at a dose of 20 mg/kg. In alloxan-induced diabetic rats, long term administration of the 80% methanolic extract of C. speciosus leaves daily for 6 weeks resulted in a significant lowering of fasting and postprandial serum glucose when compared to diabetic control rats. Conclusion: Diabetic rats group treated with C. speciosus extract displayed significantly (p&lt;0.05) decreased blood glucose level compared to the control group.&#x0D; Keywords: Alloxan, Costus speciosus, diabetes mellitus, hypoglycemia, anti-hyperglycemia

Effectiveness of analog of Humanin in ameliorating streptozotocin-induced diabetic nephropathy in Sprague Dawley rats

Diabetes mellitus (DM) is associated with numerous complications, including nephropathy, which principally occur due to hyperglycemia-induced oxidative stress and inflammation. Humanin (HN), a novel peptide generated from mitochondria, has anti-oxidant and anti-inflammatory potential as observed in different disease models. However, role of HN in diabetic nephropathy (DN) has not yet been explored. This study aimed to evaluate biochemical and molecular aspects of the effects of HN analog, Humanin-glycine ([S14G]-humanin) on streptozotocin (STZ)-induced rat model of DN. Ninety Sprague Dawley (SD) rats were randomly segregated into three groups – A (control), B (disease control) and C (treatment). DM type-I was induced in group B and C via single intra-peritoneal dose of STZ (45 mg/Kg). Seven days following STZ injection, rats were deemed diabetic if their blood glucose level was > 250 mg/dL. Subsequently, diabetic rats in group C were injected with [S14G]-humanin intra-peritoneally (0.4 mg/Kg/day) for sixteen weeks. Biochemical analysis revealed that diabetic rats had markedly elevated levels of serum glucose, creatinine, BUN, TNF-α, and kidney tissue SOD. Whereas, significant decline was detected in serum insulin and albumin levels. All these parameters were significantly reversed in group C after administering [S14G]-humanin. Moreover, qRT-PCR analysis displayed up-regulation of pro-inflammatory (IL-18, IL-6, IL-1α, IL-1β, TNF-α) and down-regulation of anti-inflammatory cytokines (IL-10, IL-1RN, IL-4) in diabetic rats (group B). [S14G]-humanin treatment significantly reversed the expression of IL-18 and IL-1α, however, change in relative expression of IL-6, IL-1β, TNF-α and anti-inflammatory cytokines was insignificant (group C). Conclusively, the findings of this study depicted potential therapeutic role of [S14G]-humanin in pre-clinical rodent model of DN.

Antidiabetic and antioxidant effect of Origanum minutiflorum O. Schwarz &amp; P. H. Davis in streptozotocin-induced diabetic rats

In this study, the antidiabetic potential of aqueous extract of Origanum minutiflorum was tested using streptozotocin induced diabetic rats. Changes in body weight, blood glucose level, biochemical parameters, antioxidant enzyme activities and histopathological examination of kidney were evaluated. The administration of aqueous extract and carvacrol to diabetic group rats caused significant decrease in blood glucose, biochemical parameters of serum and significantly increased the concentration of high density lipoprotein cholesterol. The administration of aqueous extract and carvacrol significantly increased the antioxidant enzyme activity and reduced the MDA level. The histopathological analysis of kidney showed that aqueous extract and carvacrol had possible ameliorative effect against kidney damage. Aqueous extract is also showed α-amylase and α-glucosidase inhibitor activity with high antioxidant activity. These scientific results confirm the use of O. minutiflorum as adjuvant antidiabetic therapy.

Structural Study of the Sciatic Nerve in Diabetic RafsTreated with Alium Sativurn

The diabetes mellitus has been induced in Sprague Dawely rats, by injection of alloxan 75 mg/ kg body weight, once daily for three successive days. Group of diabetic rats were treated with oral hyopgycemic (Glibenclamide) drug only and another group was treated with oral hyopgycemic (Glibenclamide) drug and Alium Sativum- garlic powder (250 mg / kg body weight, daily. Histological and histometric changes of sciatic nerve were investigated, by applying routine histological stains with specific application of osmium tetroxide for staining the nerve, detecting the structural changes and to measuring the improvement in the regeneration of the sciatic nerves. It has been found that the Alium Sativum treated group restored to certain degree the normal architectures of the sciatic nerve in diabetic rats and the improvement in thermal sensation as compared with non treated group or group treated with oral hypgycemic drug only.

In–Vitro Drug Interaction between Tulsi and Glimepride

The study was designed to determine the interaction of O. sanctum, an herbal drug used in many herbal formulations for hypoglycemic activity with Glimepiride, a sulfonylurea (SU) derivative, widely used in the treatment of type-2 diabetes, in diabetic rats. Whole study was divided into four phases in which hypoglycaemic activity with single doses of O. sanctum and glimeperide was established in single day study and repeated dose treatment of O. sanctum (7 days) followed by a single dose of glimeperide on 8th day was also established. Further the interaction between the two drugs was studied in both single and repeated treatment, i.e., the effect of single and glimeperide repeated doses treatment on O. sanctum. All the results were analysed by one way ANOVA followed by Dunnett’s‘t’ test. Rats were administered with streptozotocin for inducing diabetes and left for 2 weeks to stabilize blood glucose levels. Various doses of O. sanctum (100, 200 and 400 mg/kg) and glimeperide (½ TD, TD and 2 TD) upon single dose treatment of each in different groups of diabetic rats produced a dose dependent decrease in blood glucose levels. The maximum reduction in serum glucose was observed at 6 th h in all the groups. Single dose of O. sanctum prolonged the effect of glimepiride from 4th to 6th h without any hypoglycemic convulsions.

New Insight into Selective Serotonin Receptor Agonists in the Central Nervous System, Studied with WAY163909 in Obese and Diabetic Wistar Rats.

We investigated the effect of WAY-163909, a novel 5-hydroxytryptamine selective 2C receptor agonist on body weight, blood glucose levels, and insulin resistance in obese and diabetic Wistar rats. We used twenty male Wistar rats with obesity and obesity-induced diabetes and twenty healthy Wistar rats as a control group. Each of these groups was separated into two subgroups: one with a daily intraperitoneal application of WAY-163909 (1 mg/kg) and one without. During the study, body weight, blood glucose levels, and immunoreactive insulin were tracked. A reduction of 5.5% (p < 0.05) in body weight was registered in the rat group with diabetes and obesity and 2.56% in the control group with a daily application of WAY-163909 (1 mg/kg) at the end of the study. Decreases of 35.4% in blood glucose levels at week four in the diabetic and obese rat group with a daily application of WAY-163909 (1 mg/kg) were registered. A reduction of insulin levels of 4.1% (p < 0.05) in the diabetic and obese rats group using WAY-163909 was also observed. In our study, using WAY-163909 (1 mg/kg) led to a reduction of blood glucose levels, immunoreactive insulin, and body weight.

DEVELOPMENT AND EVALUATION OF ANTIDIABETIC POLYHERBAL TABLET USING MEDICINAL PLANTS OF TRADITIONAL USE

The aim of the present study is to develop and evaluate polyherbal tablet prepared for the management of diabetes with enhanced disintegration time. The polyherbal extract prepared using methanolic extract of selected traditionally used medicinal plants such as Adenanthera pavonina, Kigelia africana, Parkia biglandulosa and Syzygium jambose (1:1:1:2) was evaluated in alloxan monohydrate induced diabetic rat model. The polyherbal tablets were prepared by wet granulation method with excipients microcrystalline cellulose; dicalcium phosphate dehydrate and sodium starch glycolate. After preformulation studies, tablets were evaluated by using weight variation, hardness, friability and disintegration time. The diabetic rats treated with polyherbal extract were compared with the diabetic control rats group. Positive results were obtained in the observed parameters, thus favoring the use of the plants. Pre-formulation study revealed that all the evaluated parameters were found to be within acceptable limits. The weight variation of the formulated tablets was 1.43 % RSD. The disintegration time of the formulations was found to be 9.50 min. The tablets also underwent accelerated stability over the period of three months. No marked changes were observed in all the parameters evaluated during three months of accelerated stability study. Laboratory-scale preparation of polyherbal tablet can lead to new powerful and stable oral dosage formulations for diabetes mellitus and lighten the synergistic area of ​​action of herbs.

Peripheral Nerve Denervation in Streptozotocin-Induced Diabetic Rats Is Reduced by Cilostazol

Background and Objective: Our previous study demonstrated that consistent treatment of oral cilostazol was effective in reducing levels of painful peripheral neuropathy in streptozotocin-induced type I diabetic rats. As diabetic neuropathy is characterized by hyperglycemia-induced nerve damage in the periphery, this study aims to examine the neuropathology as well as the effects of cilostazol treatments on the integrity of peripheral small nerve fibers in type I diabetic rats. Materials and Methods: A total of ninety adult male Sprague-Dawley rats were divided into the following groups: (1) naïve (control) group; (2) diabetic rats (DM) group for 8 weeks; DM rats receiving either (3) 10 mg/kg oral cilostazol (Cilo10), (4) 30 mg/kg oral cilostazol (Cilo30), or (5) 100 mg/kg oral cilostazol (Cilo100) for 6 weeks. Pain tolerance thresholds of hind paws toward thermal and mechanical stimuli were assessed. Expressions of PGP9.5, P2X3, CGRP, and TRPV-1 targeting afferent nerve fibers in hind paw skin and glial cells in the spinal dorsal horn were examined via immunohistochemistry and immunofluorescence. Results: Oral cilostazol ameliorated the symptoms of mechanical allodynia but not thermal analgesia in DM rats. Significant reductions in PGP9.5-, P2X3-, CGRP, and TRPV-1-labeled penetrating nerve fibers in the epidermal layer indicated denervation of sensory nerves in the hind paw epidermis of DM rats. Denervation significantly improved in groups that received Cilo30 and Cilo100 in a dose-dependent manner. Cilostazol administration also suppressed microglial hyperactivation and increased astrocyte expressions in spinal dorsal horns. Conclusions: Oral cilostazol ameliorated hyperglycemia-induced peripheral small nerve fiber damage in the periphery of diabetic rats and effectively mitigated diabetic neuropathic pain via a central sensitization mechanism. Our findings present cilostazol not only as an effective option for managing symptoms of neuropathy but also for deterring the development of diabetic neuropathy in the early phase of type I diabetes.

A comparative study between the possible protective role of melatonin versus its combination with adipose derived-mesenchymal stem cells on experimentally induced diabetic retinopathy in adult male albino rats (Histological and immunohistochemical study)

ABSTRACT Diabetes mellitus is a metabolic disorder that can cause numerous ocular issues as well as long-term effects. In our study, we evaluate the effect of melatonin on the diabetic retinal alterations in male albino rats to the effect of melatonin combined with stem cells. 50 adult male rats were equally divided into four groups control, diabetic, melatonin, and melatonin plus stem cells. STZ, 65 mg/kg in phosphate buffered was administered intraperitoneally as a bolus to diabetic group of rats. After inducing diabetes, melatonin (10 mg/kg b.wt./day) was administered orally to the melatonin group for 8 weeks. The stem cell and melatonin group got the same dosage of melatonin as the prior group. They received an intravenous injection of (3?×?106 cell) adipose-derived MSC suspended in phosphate-buffered saline at same time of melatonin ingestion. Animals from all groups had their fundics examined. Following the injection of stem cells, samples of rat retina were collected for light and electron microscopy analyses. H&E and immunohistochemically stained sections revealed a slight improvement in group (III). At the same time, group (IV) results were comparable to those of the control group, which was supported by the findings of an electron microscope. Neovascularization was visible on fundus examination in group (II), whereas it was less noticeable in group (III) and group IV. Melatonin mildly improved the histological structure of the retina in diabetic rats, and when it was combined with adipose-derived MSC, it considerably improved the diabetic alterations.

Morphofunctional features of tissues and blood in rats against the background of experimental diabetes mellitus

Introduction. Increased susceptibility to infections in patients with type 1 diabetes mellitus is associated with impaired body protective functions as a result of suppressed immunity, increased cellular adhesion of microorganisms, susceptibility to catabolic processes. Purpose - to determine the morphofunctional features of tissues and blood in rats against the background of experimental diabetes mellitus (EDM); to investigate the effect of the extract of seven medicinal plants BNO 1030 in them. Materials and methods. Experimental studies were conducted on 20 male Wistar rats in order to determine their level of nicotineamideadeninedinucleotide (NAD), reactive oxygen species in white blood cells and superoxide dismutase. All animals were separated: the Group 1 was the control group of healthy rats, the Group 2 - the control group receiving BNO 1030 extract, the Group 3 included animals with the EDM without treatment, the Group 4 - rats with the EDM, which received the BNO 1030 extract. Results. After 6 weeks of development of the EDM, the NAD blood level in diabetic rats was reduced and reached (0.270±0.017) µmol/L, which is lower than that in the control group ((0.357±0.021) µmol/L). The group of diabetic rats treated with BNO 1030 extract showed its increase to (0.341±0.012) μmol/L compared to the group of diabetic animals, which did not receive the drug. While assessing the viability of white blood cells, it has been established that the death of most of these cells occurs by apoptosis against the background of the EDM. When BNO 1030 was used in the group of diabetic rats, the level of apoptotic cells decreased and amounted to 13.7% compared to the group, which was not administered with the drug (20.8%). In addition, the level of apoptosis in control rats, which also received BNO 1030, decreased by 3% versus the control group. Conclusions. The reduction of NAD content in tissues and blood in experimental animals with the EDM was determined, and its increase by 24% following the administration of BNO 1030 was established, which proves positive effect of the drug on the course of energy processes and glycolysis - the main route of carbohydrate metabolism. When carrying out experiments with laboratory animals, all bioethical norms and recommendations were observed. No conflict of interests was declared by the authors.

Diazoxide improves muscle function in association with improved dyslipidemia and decreased muscle oxidative stress in streptozotocin-induced diabetic rats.

Diabetes Mellitus is a chronic degenerative disease, and its main biochemical characteristic is hyperglycemia due to impaired insulin secretion, resistance to peripheral actions of insulin, or both. Hyperglycemia causes dyslipidemia and stimulates oxidative damage, leading to the main symptoms, such as fatigue and culminates in diabetic complications. Previous studies have shown that ATP-sensitive potassium channels counteract muscle fatigue and metabolic stress in healthy mouse models. To determine the effect of diazoxide on muscle strength development during diabetes, we tested the effect of diazoxide in streptozotocin-diabetic rats in muscle function, lipid profile and oxidative stress biomarkers. Wistar rats were divided into 4 groups of six animals each: (1) Control group, (2) diabetes group, (3) Control group + diazoxide, and (4) Diabetic + diazoxide (DB + DZX). 4 weeks after rats were sacrificed, soleus and extensor digitorum longus muscles (EDL) were extracted to prepare homogenates and serum was obtained for biochemical measurements. Oxidative damage was evaluated by the thiobarbituric acid method and the fluorescent for reactive oxygen species (ROS) probe 2,4-H2DCFDA, respectively. Diabetic rats with diazoxide administration showed an increase in the development of muscle strength in both muscles; in turn, the onset of fatigue was longer compared to the group of diabetic rats without treatment. Regarding the lipid profile, diazoxide decreased total cholesterol levels in the group of diabetic rats treated with diazoxide (x̅46.2mg/dL) compared to the untreated diabetic group (x̅=104.4mg/dL); secondly, diazoxide decreased triglyceride concentrations (x̅=105.3mg/dL) compared to the untreated diabetic rats (x̅=412.2mg/dL) as well as the levels of very low-density lipoproteins (x̅=20.4mg/dL vs. x̅=82.44mg/dL). Regarding the various markers of oxidative stress, the diabetic group treated with diazoxide was able to reduce the concentrations of TBARS and total reactive oxygen species as well as preserve the concentrations of reduced glutathione. Diazoxide administration in diabetic rats increases muscle strength development in EDL and soleus muscle, decreases fatigue, reduces cholesterol and triglyceride concentrations and improves oxidative stress parameters such as TBARS, ROS, and glutathione status.

The Efficacy of Tribulus terrestris and Cumminum cyminium Against Sexual Dysfunction in Diabetic Male Rats

Aim: The aim of the study was to assess the efficacy of Tribulus Terristeris and Cumminum cyminium in a standardized diabetic animal model for various pathological conditions of male sexual dysfunction (i.e., loss of libido, erectile dysfunction, and infertility) and compare these herbs with standard drugs. Background: The prevalence of sexual dysfunction is about 40-45% adult women, and 20-30% of adult men have at least one sexual dysfunction. Sexual dysfunction is more common in men with diabetes compared to non-diabetic peers. Objective: The objective of the study was to evaluate the therapeutic effect of Tribulus Terrestris (TT) and Cumminum cyminium (CC) against male sexual dysfunction with diabetes. Methods: In-vivo animal models were utilized to find out Tribulus terristeris and Cumminum cyminium. Libido study: Sexually active male Wistar rats were divided into 5 groups, i.e., control, fluoxetine treated, fluoxetine with Tribulus terristeris, fluoxetine with Cumminum cyminium and fluoxetine with bupriprion. These rats have treated for 28 days by giving different drug for different group. Erection study: Male Wistar rats were divided in 5 group (six in each) i.e. control, diabetic rats, diabetic rats treated with Tribulus terristeris, diabetic rats treated with Cumminum cyminium and diabetic treated with Insulin. The rat penile tissue was taken by scarifying the rats, and in-vitro contraction and relaxation were carried out in two-chamber student organ bath. Sperm analysis: Sperm were collected from previously scarified rats in erection study, and collected sperm were washed, count (using Neubauer haemocytometer), and studied sperm motility. Results: Cumminum cyminium showed the significant reversal of loss of desire caused by fluoxetine which was comparable to standard drug bupropion. Insulin and Tribulus terristeris treated diabetic group of rats showed the lowest capability to relax, indicating setting up of erectile dysfunction. Diabetic rats exhibited a significant reduction in sperm density, % sperm motility, and % sperm viability. Insulin and C. cyminium treated diabetic rats showed significant improvement in sperm density, % sperm motility, and % sperm viability. Conclusion: Tribulus terristeris at the dose of 100 mg/kg b.w was found to improve erectile function, whereas Cumminum cyminium at the dose of 150 mg/kg b.w was found to improve libido and sperm profile of fluoxetine treated rats.

Biological Assessment of Stevioside and Sucralose as Sucrose Substitutes for Diabetics on STZ-Induced Diabetes in Rats.

Numerous food organizations have identified excessive calorie consumption and accompanying ailments as significant health risks associated with high sugar consumption. Administering stevioside (ST), sucralose (SU), and the two synergically (SU+ST) affected normal rats' weight gain. In the current study, SU showed the highest undesired effect. Indeed, administering the three treatments to diabetic rats (DR) did not improve the rats' weight gain. Although, insulin injection synergically with the treatments improved the weight gain, as recorded after three weeks. The best-improving rate was observed in the ST group. After the administration of ST and ST+SU to the DR, the blood glucose level (GL) was positively affected, with SU having no effects on reducing the GL. A considerable reduction in serum insulin (SIL) was noted in the DR+SU group. On the contrary, ST did not negatively affect the SIL, rather an improvement was recorded. In addition, giving SU did not significantly affect the ALT level in the DR or normal rats (NR). A significant improvement in total bilirubin (TBILI) was observed when insulin was injected with ST or SU in DR groups. Further, triglycerides (TG) after administering ST, SU, or ST+SU to NR had no significant difference compared to the control group (NR). Although, the three treatments markedly but not significantly lowered TG in the DR. For total cholesterol (CHO), both DR and NR had no significant effect after the three treatments. No histopathological alterations were recorded in the NR group. Diffuse and severe atrophy of the islands of Langerhans due to depletion of their cells and mild papillary hyperplasia of the pancreatic ducts were represented by a slightly folded ductal basement membrane and newly formed ductules in STZ-DR. Simultaneous atrophy and absence of the cells of islands of Langerhans besides ductal hyperplasia were evident in DR+SU. Hyperplastic ductal epithelium and atrophic Langerhans cells were seen in DR+SU+In. Degeneration and mild atrophy were observed in the islands of Langerhans structures. There was essentially no noticeable change after utilizing ST. A slight shrinkage of the Langerhans' islets was detected in DR+ST. In DR+ST+In, no histopathological alterations in the islands of Langerhans were recorded. Congestion in the stromal blood vessels associated with degenerative and necrotic changes in the cells of the islands of Langerhans in DR+SU+ST was observed. In NR+SU, congestion of the blood vessels associated with mild atrophy in the islands of Langerhans and dilatation in stromal blood vessels was noticed. In conclusion, ST is safe, and SU should be taken cautiously, such as mixing with ST and/or taken at a very low concentration to avoid its drastic effect on the human body.