Assessing the potential fasting and postprandial mechanisms involved in the acute hypoglycemic and anti-hyperglycemic effects of four selected plants from Iran used in traditional Persian medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

Peroxisome Proliferator-Activated Receptor Alpha Stimulation Preserves Renal Tight Junction Components in a Rat Model of Early-Stage Diabetic Nephropathy.

Chronic hyperglycemia results in morphological and functional alterations of the kidney and microvascular damage, leading to diabetic nephropathy (DN). Since DN progresses to irreversible renal damage, it is important to elucidate a pharmacological strategy aimed for treating DN in the early stage. Here, we used the type 2 diabetic rat model to induce DN and show a nephroprotective effect following the stimulation of PPAR-α, which stabilized renal tight junction components claudin-2, claudin-5, and claudin-16. At 14 weeks old, streptozotocin-induced DN, evidenced by elevated creatinine clearance, proteinuria, and electrolyte excretion, was followed by an elevation in oxidative stress and increasing MMP activities affecting the integrity of claudin-2 and claudin-5. Treatment with a PPAR-α agonists decreased glucose levels in diabetic rats. In addition, we found that the expressions of CLDN-5 in glomeruli, CLDN-2 in proximal tubules, and CLDN-16 in the thick ascending limb of the loop of Henle were increased after treatment. As a result, renal function improved, while the oxidative stress and enzymatic activity of MMP-2 and MMP-9 decreased. In conclusion, PPAR-α stimulation prevented the decrease in claudins through a mechanism involving a correction of hyperglycemia, decreasing it in kidney oxidative stress and MMP-2 and MMP-9 activities, showing a promising nephroprotective action in the early stage of DN.

Hyperbaric oxygen therapy prevents epithelial atrophy in distal tubules and TGF-ß1 overexpression in diabetic rat kidneys.

Diabetic nephropathy (DN) is one of the most relevant and prevalent microvascular complications associated with Diabetes Mellitus. In recent years, hyperbaric oxygen therapy (HBO) has been used to mitigate tissue damage caused by hypoxia, thereby attenuating inflammatory processes. This study aimed to explore morphological aspects associated with DN in rats subjected to HBO. Forty-eight Wistar rats were divided into the following groups: C (normoglycemic animals), n = 12; C + HBO (normoglycemic animals submitted to HBO), n = 12; D (diabetic animals) n = 12; D + HBO (diabetic animals submitted to HBO), n = 12. The C + HBO and D + HBO groups were daily treated with HBO at 2.5 atmospheres absolute pressure (ATA) for 60 min, 5 days a week, for 5 weeks. Kidneys were collected for assessment of structural changes in the tissue parenchyma, assessment of renal fibrosis and renal protein expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-ß1 (TGF-ß1). Our results showed that group D had hyperglycemia and weight loss, and that there was also an increase in the renal corpuscle, Bowman's space, and distal tubular epithelium, as well as accumulation of collagen. HBO administration effectively prevented glomerular hypertrophy and attenuated the expression of TNF-α and TGF-ß1. It also positively affected renal tubules, inhibiting the development of tubular atrophy. These findings suggest that HBO was effective in attenuating the initial alterations observed in DN.

Biochemical and histological effects of the subchronic treatment with a beer containing Baccharis dracunculifolia in an experimental model of diabetes.

This article reports the development of a beer made with Baccharis dracunculifolia and its application in an experimental model of diabetes. Initially, the production of the beverage was standardized in order to incorporate the plant extract properly. Next, the beer was analyzed by the UHPLC-MS to identify the substances present. Among others, caffeic acid (5.85 mg / L), m-coumaric acid (5.16 mg / L), pinocembrin (2.99 mg / L), chrysin (10.86 mg / L), myricetin (1.73 mg / L) and spathulenol (9.30 mg / L) were found. Animal tests indicate improvement in biochemical and histological parameters of STZ-induced Wistar rats that ingested the beer made with the plant. The antidiabetic potential of this beverage was observed in the different tests that evaluated insulin resistance and the decrease of the clinical manifestations of diabetes in animals. The use of the drink as an adjunct in clinical treatments for DM2 may be useful, especially in suppressing the oxidative damage caused by the disease.

Organic vs. inorganic nitrates: Metabolic and vascular outcomes in STZ-induced diabetes in mice.

BACKGROUND: Diabetic animals often display dysregulated nitric oxide (NO) metabolism, contributing to vascular dysfunction. This study evaluates the metabolic and vascular effects of organic nitrate isosorbide mononitrate (ISMN) versus inorganic sodium nitrate (NaNO3) in mice with type 1 diabetes mellitus (T1DM) induced by streptozotocin (STZ). EXPERIMENTAL APPROACH: T1DM was induced in male C57Bl6 mice with STZ ip and confirmed by fasting glucose. Mice were treated with ISMN (10 mg·kg-1) or NaNO3 (85 mg·L-1) for 14 days. A combination of in vivo, in vitro, and ex vivo studies assessed cardiometabolic benefits. RESULTS: Both nitrates reduced blood and urinary hyperglycemia in T1DM mice, with ISMN exhibiting more significant reductions in blood glucose. ISMN and NaNO3 similarly reduced water and food intake, urinary volume, glucose intolerance, and insulin resistance while increasing insulin and nitrite levels in serum and urine. Both nitrates improved endothelium-independent vascular function and attenuated reactive oxygen species (ROS) while increasing NO levels in the aortic rings of T1DM mice. Furthermore, both nitrates similarly reduced mean arterial pressure in T1DM mice. CONCLUSION AND IMPLICATIONS: ISMN and NaNO3 have demonstrated comparable hypotensive and antioxidant effects, offering metabolic and vascular benefits in STZ-TDM1 mice. The more pronounced reduction in blood glucose with ISMN treatment compared to NaNO3 is particularly promising. The antihyperglycemic effects of both nitrates were linked to increased serum insulin levels and enhanced insulin sensitivity. These results provide a foundation for future clinical studies to evaluate the potential of ISMN or NaNO3 as antidiabetogenic and antihypertensive adjuvant therapies in diabetic patients.

Cratylia mollis lectin reduces inflammatory burden induced by multidrug-resistant Staphylococcus aureus in diabetic wounds.

In diabetes, tissue repair is impaired, increasing susceptibility to Staphylococcus aureus infections, a pathogen commonly found in wounds. The emergence of S. aureus strains that are highly resistant to antimicrobial agents highlights the urgent need for alternative therapeutic options. One promising candidate is Cramoll (Cratylia mollis seed lectin), known for its immunomodulatory, mitogenic, and healing properties. However, its efficacy in infected diabetic wounds remains unexplored. This study evaluated the effects of topical Cramoll treatment on diabetic wounds infected by S. aureus. Diabetic Swiss mice (induced by streptozotocin) were subjected to an 8-mm wound on the back and subsequently infected with a suspension of multidrug-resistant S. aureus. During the treatment period, the wounds were clinically evaluated for inflammation and the area of injury. After seven days, samples were collected from the wounds to quantify the bacterial load and histopathological and immunological analyses. Wounds infected by S. aureus exhibited more pronounced areas and severity indices, which were significantly reduced by Cramoll treatment (p < 0.05). Histopathological analysis revealed a reduction in inflammatory cells and an increase in revascularization with Cramoll treatment (p < 0.05). Cramoll also promoted greater collagen production compared to controls (p < 0.05). Furthermore, Cramoll treatment significantly reduced the S. aureus load in wounds (p < 0.0001), decreased TNF-α and IL-6 levels in infected wounds, and increased ERK pathway activation (p < 0.05). In conclusion, Cramoll lectin improves the healing of diabetic wounds, and these results contribute to the understanding of Cramoll healing mechanisms, reinforcing its potential as a healing agent in various clinical conditions.

Prolonged Photobiomodulation with Deep Red Light Mitigates Incipient Retinal Deterioration in a Mouse Model of Type 2 Diabetes.

Diabetic retinopathy is a prevalent complication of type 2 diabetes mellitus, characterized by progressive damage to the retinal structure and function. Photobiomodulation therapy, using red or near-infrared light, has been proposed as a non-invasive intervention to mitigate retinal damage, but has been tested generally with short-term stimuli. This study aimed to evaluate the effects of prolonged photobiomodulation with deep red light on retinal structure and function in a type 2 diabetes mouse model. Transgenic LepRdb/J (db/db) mice were exposed to photobiomodulation therapy via LED devices emitting 654 nm light for 12 h daily over ten weeks and compared to untreated mice. Retinal function was evaluated by flash electroretinography, while structural changes were assessed through histology and immunohistochemistry to detect astro- and microgliosis. At 33 weeks of age, db/db mice were obese and severely diabetic, but exhibited only incipient indicators of retinal deterioration. Electroretinogram b-wave peak latencies were prolonged at intermediate flash intensities, while the outer plexiform layer displayed significantly elevated IBA1 expression. Photobiomodulation therapy prevented these two markers of early retinal deterioration but had no effect on other morphological and functional parameters. Photobiomodulation is well-tolerated and maintains potential as a complementary treatment option for diabetic retinopathy but requires further optimization of therapeutic settings and combinatory treatment approaches.

Lithium-containing 45S5 Bioglass-derived glass-ceramics have antioxidant activity and induce new bone formation in a rat preclinical model of type 1 diabetes mellitus.

Diabetes mellitus (DM) has been associated with complications that affect the skeletal system, such as alterations in bone repair, osteoporosis, and an increased risk of fractures. In this context, the use of biomaterials able to promote osteogenic differentiation and, at the same time, limit the oxidative stress induced by DM offers a novel perspective to ensure the repair of diabetic bone tissue. Since lithium (Li) has been recently identified as a biologically active ion with osteogenic and antioxidant properties, the localized and controlled release of Li ions from bioactive glass-ceramic materials represents a promising therapeutic alternative for the treatment of bone lesions in DM. Thus, the aim of this study was to evaluate the potential osteogenic and antioxidant effects of glass-ceramic microparticles derived from a 45S5-type bioactive glass (Bioglass) containing (% by weight) 45% SiO2, 24.5% Na2O, 24.5% CaO, and 6% P2O5, in which Na2O was partially substituted by 5% of Li2O (45S5.5Li), in an experimental model of type 1 DM (DM1). The results obtained demonstrate, for the first time, that both 45S5 and 45S5.5Li glass-ceramic microparticles possess antioxidant activity and stimulate bone formationin vivoboth under physiological conditions and under experimental DM1 in rats. In this sense, they would have potential application as inorganic osteogenic agents in different strategies of bone tissue regenerative medicine.

Harmful Effects on the Hippocampal Morpho-Histology and on Learning and Memory in the Offspring of Rats with Streptozotocin-Induced Diabetes.

Learning alterations in the child population may be linked to gestational diabetes as a causal factor, though this remains an open and highly controversial question. In that sense, it has been reported that maternal hyperglycemia generates a threatening condition that affects hippocampal development in offspring. The pyramidal cells of the CA3 subfield, a key structure in learning and memory processes, are particularly important in cognitive deficiencies. We evaluate the effect of the hyperglycemic intrauterine environment on hippocampal histomorphometry in offspring, correlating it with spatial learning and memory, as well as the morphology of dendrites and spines in 30-day-old pups (P30). The maternal hyperglycemia affected the body weight, height, and brain size of fetuses at 21 days of gestation (F21), newborn pups (P0) and P30 pups from diabetic rats, which were smaller compared to the control group. Consequently, this resulted in a decrease in hippocampal size, lower neuronal density and cytoarchitectural disorganization in the CA3 region of the hippocampus in the offspring at the three ages studied. The behavioral tests performed showed a direct relationship between morpho-histological alterations and deficiencies in learning and memory, as well as alterations in the morphology of the dendrites and spines. Therefore, knowing the harmful effects caused by gestational diabetes can be of great help to establish therapeutic and educational strategies that can help to improve learning and memory in children.

Evaluation of the Effect of an α-Adrenergic Blocker, a PPAR-γ Receptor Agonist, and a Glycemic Regulator on Chronic Kidney Disease in Diabetic Rats.

Diabetic nephropathy (DN) is a globally widespread complication of diabetes mellitus (DM). Research indicates that pioglitazone and linagliptin mitigate the risk of DN by reducing inflammation, oxidative stress, and fibrosis. The role of tamsulosin in DN is less studied, but it may contribute to reducing oxidative stress and inflammatory responses. The protective effects of combining pioglitazone, linagliptin, and tamsulosin on the kidneys have scarcely been investigated. This study examines the individual and combined effects of these drugs on DN in Wistar rats. Diabetic rats were treated with tamsulosin, pioglitazone, and linagliptin for six weeks. We assessed food and water intake, estimated glomerular filtration rate (eGFR), histological markers, urea, creatinine, glucose, NF-κB, IL-1, IL-10, TGF-ß, and Col-IV using immunofluorescence and qPCR. The DN group exhibited hyperglycaemia, reduced eGFR, and tissue damage. Tamsulosin and linagliptin improved eGFR, decreased urinary glucose, and repaired tissue damage. Pioglitazone and its combinations restored serum and urinary markers and reduced tissue damage. Linagliptin lowered serum creatinine and tissue injury. In conclusion, tamsulosin, linagliptin, and pioglitazone demonstrated renoprotective effects in DN.

Effect of Buddleja cordata Leaf Extract on Diabetic Nephropathy in Rats.

One of complications of diabetes mellitus is diabetic nephropathy. In Mexico, in traditional medicine, Buddleja cordata Humb. Bonpl. & Kunth, ("tepozán blanco") is a shrub plant used for the treatment of rheumatic diseases, postpartum bath, stomachache, skin burns, diarrhea in children, sores, and cancer. Objectives: We examined the effect of methanol extract of leaves of B. cordata on the expression of pro-inflammatory cytokines and its antioxidant effects in diabetic nephropathy. Methods: We used the streptozotocin-induced diabetes mellitus model in rats; these were treated with methanol extract from leaves of B. cordata at 50 and 100 mg/kg (orally) for 4 weeks. Kidney weight/total body weight ratio and proteins/DNA, proteinuria and creatinine clearance, Western blot of nuclear factor κΒ (NFkB) p65 (cytoplasm and nucleus), peroxisome proliferator activated receptor gamma (PPARγ), and activities of glutathione peroxidase, superoxide dismutase, and catalase were determined.

Diabetic rats skin wounds treated with heterologous fibrin sealant followed by photobiomodulation therapy.

Diabetes mellitus is characterized by elevated blood glucose levels causing sometimes impairment of the body's ability to repair itself. Promising treatments for tissue repair have included photobiomodulation therapy and heterologous fibrin biopolymer (HFB). This study aimed to evaluate the impact of photobiomodulation therapy by LED, both as a standalone treatment and in conjunction with heterologous fibrin biopolymer in treatment of skin lesions of diabetic rats. Diabetes was induced using alloxan. Full-thickness skin wounds were induced on the backs of 56 Wistar rats, which were randomly allocated into four groups: control group, heterologous fibrin biopolymer group, photobiomodulation therapy by LED group, and photobiomodulation therapy by LED combined with heterologous fibrin biopolymer group. The treatments spanned two experimental periods, lasting 7 and 14 days. Notably, the HFB group exhibited results similar to those of the LED group concerning wound regression, while demonstrating superior resistance to healing. Interestingly, the LED + HFB group showed greater skin damage at 7 days, but an improved repair process at 14 days compared to the control group. The findings indicate that combining photobiomodulation by LED with HFB did not enhance wound healing in diabetic rats beyond the effects of each treatment alone. Both treatments were effective individually, with HFB showing particular strength in promoting collagen maturation and improving tissue biomechanical properties. This study contributes to the ongoing body of research on skin repair with this innovative HFB. Future clinical trials will be essential to validate this proposition.

Healing effect of curcumin on tooth extraction sockets in diabetic rats.

OBJECTIVE: Diabetes mellitus (DM) delays wound healing, including those following tooth extractions. Curcumin (CCM) can promote soft tissue and bone healing. The present study investigates the healing effects of CCM on tooth extraction sockets in diabetic rats. METHODOLOGY: Ninety-six male Wistar rats were divided into the following four groups: Control+Corn Oil (CO), Control+CCM, DM+CO, and DM+CCM. Each group was subdivided into 7-, 14-, and 28-day time point subgroups comprising eight rats. All animals had their maxillary first molars extracted. CCM-treated rats received 100 mg/kg of CCM orally for 7, 14, and 28 days. The lesion area was evaluated using macroscopic analyses, whereas socket healing was assessed by hematoxylin and eosin staining. Keratinocyte growth factor (KGF), Runt-related transcription factor 2 (Runx2), and collagen type I (COL1) expression levels were obtained using quantitative polymerase chain reaction (qPCR). Bone healing was analyzed by means of microcomputed tomography (µCT). RESULTS: After 7 days, the groups showed no significant differences in lesion area and by day 14, no lesions were present. CCM treatment increased KGF mRNA expression in diabetic rats; however, diabetic rats showed delayed bone healing unrelated to CCM. CCM treatment resulted in increased Runx2 mRNA expression only in control rats, whereas COL1 mRNA expression remained unaffected by CCM. CONCLUSION: CCM shows potential as a soft tissue healing enhancer in diabetic rats and could serve as an additional treatment to promote soft tissue repair in diabetic individuals. Although CCM did not impact alveolar bone healing, it may enhance bone healing in other skeleton regions.

Captopril inhibits the overproduction of proopiomelanocortin and adrenocorticotropic hormone in the pituitary gland of male diabetic mice in close relationship with an increase in glucocorticoid receptor expression.

Prior investigation shows that diabetic patients present hypothalamus-pituitary-adrenal (HPA) axis hyperactivity related to impaired negative feedback. This study investigates the effect of Captopril on the overproduction of adrenocorticotropic hormone (ACTH) and its precursor proopiomelanocortin (POMC) in the pituitary gland of male diabetic mice. Diabetes was induced by intravenous injection of alloxan into fasted Swiss-webster mice, and the animals were treated with Captopril for 14 consecutive days, starting 7 days post-diabetes induction. Plasma corticosterone levels were evaluated by ELISA, while pituitary gland expressions of angiotensin-II type 1 receptor (AT1), angiotensin-II type 2 receptor (AT2), ACTH, Bax, Bcl-2, KI-67, POMC, and glucocorticoid receptor (GR) were evaluated using immunohistochemistry or Western blot. Diabetic mice showed pituitary gland overexpression of AT1, without altering AT2 levels, which were sensitive to Captopril treatment. Furthermore, diabetic mice presented hypercortisolism, along with an increase in the number of corticotroph cells, POMC and ACTH expression, and number of proliferative cells, and a decrease of GR expression in the pituitary gland. In addition, treatment with Captopril reduced systemic corticosterone levels, corticotroph and proliferative cell numbers, and Bcl-2, POMC, and ACTH expression in the pituitary gland of diabetic mice, besides increasing the expression of Bax and GR. In conclusion, these findings show that Captopril is a promising therapy for treating complications associated with HPA axis hyperactivity in diabetic patients, in a mechanism probably related to the downregulation of POMC production in the pituitary gland and subsequent reduction of systemic corticosterone levels.

Mesenchymal stem cells from human umbilical cord decrease inflammation and increase vascularization of induced apical periodontitis model in diabetes mellitus rats.

OBJECTIVES: to evaluate inflammation and vascularization in a model of apical periodontitis in diabetic Wistar rats through histopathological examination of blood vessels and immunohistochemical examination of interleukin 1b (IL-1b) and tumor necrosis factor-a (TNF-a). METHODOLOGY: Diabetes was induced in 20 Wistar rats using multiple low-dose injections of streptozotocin (STZ) until blood glucose levels stabilized above 300 mg/dL, confirmed by glucometer. Under anesthesia, apical periodontitis was induced in the right mandibular first molars. After preparing the access cavity and extirpating pulp and canal, the teeth were left open. Apical periodontitis was projected seven days afterwards and the Wistar rats were assigned in random into four groups, each group consisting of five rats. The first group (C14) was euthanized 14 days post-induction, while the second group (C28) was euthanized 28 days later, serving as controls. The third group (T14) received mesenchymal stem cells from human umbilical cords and was euthanized after 14 days, while the fourth group (T28) received mesenchymal stem cells from human umbilical cord and was euthanized after 28 days. The number of blood vessels and the expressions of IL-1b and TNF-a were analyzed. Data were evaluated with ANOVA and by Tukey's HSD test, with significance at p<0.05. RESULTS: Both control and treatment groups showed a significant increase in vascularization in the apical periodontal area of apical periodontitis in the control and treatment groups at 14 and 28 days (p<0.05). A significant reduction of IL-1b and TNF-a levels was found in the mesenchymal stem cells treatment groups when compared to control groups (p<0.05). CONCLUSION: Our findings support the use of mesenchymal stem cells from human umbilical cords to decrease inflammation and increase vascularization in an induced apical periodontitis model in diabetes mellitus Wistar rats.

Photobiomodulation and Physical Exercise Modulate of Cell Survival Proteins in the Skeletal Muscle of Rats with Heart Failure and Diabetes Mellitus.

Introduction: Heart failure (HF) and type 2 diabetes mellitus (DM2) are global health problems that often lead to muscle atrophy. These conditions are associated with increased autophagy and apoptosis in the muscle cells, resulting in decreased muscle mass. Physical exercise associated with photobiomodulation (PBM) seems promising to attenuate the skeletal muscle changes caused by HF and DM2, due to its direct effects on mitochondria, which may result in an increase in antioxidant capacity. Objective: To verify the influence of physical exercise and the association with PBM on autophagy, apoptosis, and cell survival signaling pathways in myocytes from rats with HF and DM2. Materials and Methods: Male rats were assigned to one of four groups: control (CT), HF+DM (disease model), exercise+HF+DM (EX+HF+DM), and EX+HF+DM+PBM (EX+HF+DM+PBM). To induce DM2, we administered streptozotocin (STZ) (0.25 mL/kg, intraperitoneally). HF was induced by coronary ligation. One week post-induction, an 8-week aerobic exercise and PBM protocol was initiated. Western blot analysis was used to measure the expression of apoptosis-related proteins and autophagy. Results: The EX+HF+DM+PBM group showed a substantial increase in Nrf2, p-AKT, and LC3-I levels compared to the HF+DM group. Conclusions: These findings suggest that physical exercise combined with PBM can upregulate proteins that promote myocyte survival in rats with HF and DM2.

Atorvastatin Accelerates Alveolar Bone Loss in Type 1 Diabetic Rats Submitted to Periodontitis.

Periodontal bone loss is potentiated by diabetes. Despite the beneficial anti-inflammatory and antiresorptive effects of Atorvastatin (ATV) on periodontitis, it has been reported to increase the risk of diabetes, which may modify the course of periodontal disease. Therefore, this study aimed to evaluate the effect of ATV on alveolar bone in rats with periodontitis and diabetes. For this, 72 Wistar rats were divided into groups: Naïve (N) not submitted to any procedure; Experimental periodontitis (EP) group submitted to ligature-induced periodontitis; diabetes mellitus (DM), submitted to EP and receiving single dose of streptozotocin (60 mg/kg, i.p.) after 12 hours of fasting; and ATV DM, submitted to EP and DM and receiving orally 27 mg/kg of ATV, 30 minutes before ligature placement, and continued daily until the 11th day. Animals from EP and DM received saline solution 0.9% as placebo. Glycemic levels measured in all animals and then were euthanized. Maxillae were collected for macroscopic, micro-tomographic, and microscopic analyses. DM caused intense bone loss (60%), characterized by a reduction in trabecular thickness and bone volume. DM reduced osteoblasts, increasing osteoclast counts, and induced an inflammatory infiltrate in the periodontium. ATV was found ineffective in protecting bone in diabetic rats, exacerbating bone loss by 21%. Additionally, ATV significantly increased blood glucose levels. In summary, ATV did not prevent alveolar bone loss or modulate inflammation in DM animals undergoing EP. ATV also increased blood glucose levels in these animals. Therefore, the systemic use of ATV in uncontrolled diabetic conditions should be carefully evaluated.

Isoflurane preconditioning protects against renal ischemia/reperfusion injury in diabetes via activation of the Brg1/Nrf2/HO-1 signaling pathway.

PURPOSE: To examine whether isoflurane preconditioning (IsoP) has a protective effect against renal ischemia/reperfusion injury (I/RI) in diabetic conditions and to further clarify the underlying mechanisms. METHODS: Control and streptozotocin-induced diabetic rats were randomly assigned to five groups, as follows: normal sham, normal I/R, diabetic sham, diabetic I/R, and diabetic I/R + isoflurane. Renal I/RI was induced by clamping renal pedicle for 45 min followed by reperfusion for 24 h. IsoP was achieved by exposing the rats to 2% isoflurane for 30 min before vascular occlusion. Kidneys and blood were collected after reperfusion for further analysis. Renal histology, blood urea nitrogen, serum creatinine, oxidative stress, inflammatory cytokines, and renal cell apoptosis were assessed. Furthermore, the expression of brahma related gene 1 (Brg1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and nuclear factor-κB (NF-κB) were determined. RESULTS: Compared with control, diabetic rats undergoing I/R presented more severe renal injury, oxidative stress, inflammatory reaction, and apoptosis with the impairment of Brg1/Nrf2/HO-1 signaling. All these alterations were significantly attenuated by pretreatment with isoflurane. CONCLUSIONS: These findings suggest that isoflurane could alleviate renal I/RI in diabetes, possibly through improving Brg1/Nrf2/HO-1 signaling.

Diabetes induces modifications in costameric proteins and increases cardiomyocyte stiffness.

Several studies have demonstrated that diabetes mellitus can increase the risk of cardiovascular disease and remains the principal cause of death in these patients. Costameres connect the sarcolemma with the cytoskeleton and extracellular matrix, facilitating the transmission of mechanical forces and cell signaling. They are related to cardiac physiology because individual cardiac cells are connected by intercalated discs that synchronize muscle contraction. Diabetes impacts the nanomechanical properties of cardiomyocytes, resulting in increased cellular and left ventricular stiffness, as evidenced in clinical studies of these patients. The question of whether costameric proteins are affected by diabetes in the heart has not been studied. This work analyzes whether type 1 diabetes mellitus (T1DM) modifies the costameric proteins and coincidentally changes the cellular mechanics in the same cardiomyocytes. The samples were analyzed by immunotechniques using laser confocal microscopy. Significant statistical differences were found in the spatial arrangement of the costameric proteins. However, these differences are not due to their expression. Atomic force microscopy was used to compare intrinsic cellular stiffness between diabetic and normal cardiomyocytes and obtain the first elasticity map sections of diabetic living cardiomyocytes. Data obtained demonstrated that diabetic cardiomyocytes had higher stiffness than control. The present work shows experimental evidence that intracellular changes related to cell-cell and cell-extracellular matrix communication occur, which could be related to cardiac pathogenic mechanisms. These changes could contribute to alterations in the mechanical and electrical properties of cardiomyocytes and, consequently, to diabetic cardiomyopathy.NEW & NOTEWORTHY The structural organization of cardiomyocyte proteins is critical for their efficient functioning as a contractile unit in the heart. This work shows that diabetes mellitus induces significant changes in the spatial organization of costamere proteins, t tubules, and intercalated discs. We obtained the first elasticity map sections of living diabetic cardiomyocytes. The results show statistical differences in the map sections of diabetic and control cardiomyocytes, with diabetic cardiomyocytes being stiffer than normal ones.

Melatonin associated with bacterial cellulose-based hydrogel improves healing of skin wounds in diabetic rats.

PURPOSE: To describe the effects of melatonin associated with bacterial cellulose-based hydrogel on healing of skin wounds in diabetic rats. METHODS: Streptozotocin was used to induce diabetes in Wistar rats. After wound induction, animals were randomly divided into groups GC, GDCC, GDCB, and GDMCB. Animals were evaluated in days 3, 7, and 14 for the following variables: glycemic levels, histopathological and histochemical analyses, healing rate, morphometry and C-reactive protein. RESULTS: There was no change in glycemic levels in the diabetic animals as a result of the treatments; histopathological analyses showed better healing in GDCB and GDMCB groups, as well as histochemistry; at day 14, the highest healing rate was observed in animals from the GDMCB group, reaching almost 100%; morphometry revealed a significant increase of fibroblasts and reduction of macrophages and blood vessels in lesions treated with bacterial cellulose associated or not with melatonin when compared to the other experimental groups. There was also an increase in C-reactive protein in GDCC group at day 14. CONCLUSION: Bacterial cellulose-based dressings associated with systemic melatonin showed beneficial results in experimentally induced wounds in diabetic rats, favoring the healing process.