Streptozotocin-induced Diabetic Rats Research Articles

Antidiabetic Effects of Coffee Silverskin Extract in Streptozotocin-Induced Diabetic Wistar Rats

Antidiabetic Effects of Coffee Silverskin Extract in Streptozotocin-Induced Diabetic Wistar Rats

Nephroprotective Effect of Hibiscus Sabdariffa Leaf Flavonoid Extracts via KIM-1 and TGF-1β Signaling Pathways in Streptozotocin-Induced Rats.

Diabetes-induced kidney damage represents a substantial health hazard, emphasizing the imperative to explore potential therapeutic interventions. This study investigates the nephroprotective activity of flavonoid-rich extracts from Hibiscus sabdariffa leaves in streptozotocin-induced diabetic rats. The flavonoid-rich extracts of H. sabdariffa leaves was obtained using a standard procedure. The animals were induced with streptozotocin and thereafter treated with both low (LDHSFL) and high doses (HDHSFL) of flavonoid-rich extracts from H. sabdariffa leaves and metformin (MET), and other groups are diabetic control (DC) and normal control (NC). The study assesses diverse renal parameters, encompassing kidney redox stress biomarkers, serum electrolyte levels, kidney inflammatory biomarkers, serum concentrations of creatinine, urea, and uric acid, kidney phosphatase activities, renal histopathology, and relative gene expressions of kidney injury molecule-1 (KIM-1) and transforming growth factor beta-1 (TGF-1β), comparing these measurements with normal and diabetic control groups (NC and DC). The findings indicate that the use of extracts from H. sabdariffa leaves markedly (p < 0.05) enhanced renal well-being by mitigating nephropathy, as demonstrated through the adjustment of various biochemical and gene expression biomarkers, indicating a pronounced antioxidative and anti-inflammatory effect, improved kidney morphology, and mitigation of renal dysfunction. These findings suggest that H. sabdariffa leaf flavonoid extracts exhibit nephroprotective properties, presenting a potential natural therapeutic approach for the treatment of diabetic nephropathy.

Nanoparticle-mediated delivery of tetrahydrobiopterin restores endothelial function in diabetic rats

Endothelial dysfunction, underlying the vascular complications of diabetes and other cardiovascular disorders, may result from uncoupling of endothelial nitric oxide synthase (eNOS) activity due to decreased levels of tetrahydrobiopterin (BH4), a critical co-factor for eNOS. Some clinical trials attempting to deliver exogenous BH4 as a potential therapeutic strategy in vascular disease states have failed due to oxidation of BH4 in the circulation. We sought to develop a means of protecting BH4 from oxidation while delivering it to dysfunctional endothelial cells. Polymeric and solid lipid nanoparticles (NPs) loaded with BH4 were delivered by injection or oral gavage, respectively, to streptozotocin-induced diabetic rats. BH4 was measured in coronary endothelial cells and endothelium-dependent vascular reactivity was assessed in vascular rings. Lymphatic uptake of orally delivered lipid NPs was verified by sampling mesenteric lymph. BH4-loaded polymeric NPs maintained nitric oxide production by cultured endothelial cells under conditions of oxidative stress. BH4-loaded NPs, delivered via injection or ingestion, increased coronary endothelial BH4 concentration and improved endothelium-dependent vasorelaxation in diabetic rats. Pharmacodynamics assessment indicated peak concentration of solid lipid NPs in the systemic bloodstream 6 hours after ingestion, with disappearance noted by 48 hours. These studies support the feasibility of utilizing NPs to deliver BH4 to dysfunctional endothelial cells to increase nitric oxide bioavailability. BH4-loaded NPs could provide an innovative tool to restore redox balance in blood vessels and modulate eNOS-mediated vascular function to reverse or retard vascular disease in diabetes.

Unveiling the presence of insulin-like antidiabetic proteins in potato: A wholesome food

A study was taken up to explore the possibilities for the presence of Insulin like protein in potato tubers. The serological based Direct antigen coating-Enzyme linked immune sorbent assay (DAC-ELISA) clearly detected and quantified the presence of insulin like proteins in dormant and sprouted potato tubers. Presence of ILP was further confirmed in dormant or sprouted potato tuber by Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis where an expected size of approximately 10 kDa corresponding to that of Insulin standard was recorded. In the second phase, an in vivo antihyperglycemic activity was carried out by administering the lyophilized powder derived from the tubers of Indian potato varieties to streptozotocin-induced diabetic rats. Among the varieties, Kufri Surya and Kufri Pushkar reduced the blood sugar level to 29.7% and 18% respectively, whereas, the metformin drug reduced the blood sugar level to 23.6%. In addition, the antioxidant and antidiabetic compounds (other than insulin like proteins) of the same varieties were also studies where Kufri Surya was found to be rich in nutrients and antidiabetic compounds. This is the first report on presence of insulin like proteins in the tubers of Indian potato varieties. The study presents a lead to explore the genes expressing insulin like proteins and subsequent utilization in developing specialty insulin rich potato varieties either by biotechnological based gene transfer approaches or by traditional breeding approach.

Retraction Note: Therapeutic effect of melatonin-loaded chitosan/lecithin nanoparticles on hyperglycemia and pancreatic beta cells regeneration in streptozotocin-induced diabetic rats

Retraction Note: Therapeutic effect of melatonin-loaded chitosan/lecithin nanoparticles on hyperglycemia and pancreatic beta cells regeneration in streptozotocin-induced diabetic rats

Therapeutic Potential of 4-Hexylresorcinol in Preserving Testicular Function in Streptozotocin-Induced Diabetic Rats.

It is known that many diabetic patients experience testicular atrophy. This study sought to investigate the effect of 4-hexylresorcinol (4HR) on testicular function in rats with streptozotocin (STZ)-induced diabetes, focusing on testicular weight, sperm motility, histological alterations, and serum testosterone levels to understand the efficacy of 4HR on testes. Our findings reveal that 4HR treatment significantly improves testicular health in diabetic rats. Notably, the STZ group exhibited a testicular weight of 1.22 ± 0.48 g, whereas the STZ/4HR group showed a significantly enhanced weight of 1.91 ± 0.26 g (p < 0.001), aligning closely with the control group's weight of 1.99 ± 0.17 g and the 4HR group's weight of 2.05 ± 0.24 g, indicating no significant difference between control and 4HR groups (p > 0.05). Furthermore, the STZ/4HR group demonstrated significantly improved sperm motility compared to the STZ group, with apoptotic indicators notably reduced in the STZ/4HR group relative to the STZ group (p < 0.05). These results underscore the therapeutic potential of 4HR for maintaining testicular function under diabetic conditions.

A Non-Toxic Binuclear Vanadium(IV) Complex as Insulin Adjuvant Improves the Glycemic Control in Streptozotocin-Induced Diabetic Rats.

Diabetes mellitus (DM) complications are a burden to health care systems due to the associated consequences of poor glycemic control and the side effects of insulin therapy. Recently. adjuvant therapies, such as vanadium compounds, have gained attention due to their potential to improve glucose homeostasis in patients with diabetes. In order to determine the anti-diabetic and antioxidant effects of the oxidovanadium(IV) complex (Et3NH)2[{VO(OH}2)(ox)2(µ-ox)] or Vox2), rats with streptozotocin (STZ)-induced diabetes were treated with 30 and 100 mg/kg of Vox2, orally administered for 12 days. Vox2 at 100 mg/kg in association with insulin caused a 3.4 times decrease in blood glucose in STZ rats (424 mg/dL), reaching concentrations similar to those in the normoglycemic animals (126 mg/dL). Compared to insulin alone, the association with Vox2 caused an additional decrease in blood glucose of 39% and 65% at 30 and 100 mg/kg, respectively, and an increased pancreatic GSH levels 2.5 times. Vox2 alone did not cause gastrointestinal discomfort, diarrhea, and hepatic or renal toxicity and was not associated with changes in blood glucose level, lipid profile, or kidney or liver function. Our results highlight the potential of Vox2 in association with insulin in treating diabetes.

Co-administration of “L-Lysine, Vitamin C, and Zinc” increased the antioxidant activity, decreased insulin resistance, and improved lipid profile in streptozotocin-induced diabetic rats

PurposeWe previously showed the beneficial effect of L-Lysine (Lys), a chemical chaperone, on reducing diabetic complications in diabetic rats and type 2 diabetic patients. Herein, we evaluated the effect of Lys co-administration with Vitamin C and Zinc (Lys+VC+Zn), in diabetic rats. MethodsThe streptozotocin (50 mg/Kg) was injected into male adult Wistar rats to induce diabetes. Then, different groups of normal and diabetic rats were treated with Lys and Lys+VC+Zn for five months. So, there were 0.1 % Lys in the drinking water of both groups. The control groups received water alone. During the experiment, the body weight, and various parameters were determined in the blood, serum/plasma, and urine of the rats. ResultsThe determination of biochemical indexes confirmed diabetes induction and its complications in rats. Treatment with either Lys or Lys+VC+Zn resulted in reduced blood glucose and protein glycation (decreasing AGEs and HbA1c), increased insulin secretion, alleviated insulin resistance and HOMA-IR, improved lipid profile and HDL functionality (LCAT and PON1), enhanced antioxidant status (FRAP and AOPP), improved kidney function (decreased microalbuminuria, serum urea, and creatinine), and increased chaperone capacity (HSP70). Lys+VC+Zn showed better effects on these parameters than Lys alone. ConclusionsThe results of this study indicated that co-administration of Lys, a chemical chaperone, with two antioxidants (VC and Zn) potentiates its antidiabetic effects and prevent diabetic complications in rat model of diabetes.

Phloretamide Protects against Diabetic Kidney Damage and Dysfunction in Diabetic Rats by Attenuating Hyperglycemia and Hyperlipidemia, Suppressing NF-κβ, and Upregulating Nrf2.

Potent hypoglycemic and antioxidant effects were recently reported for the apple-derived phenolic compound phloretamide (PLTM). The renoprotective effects of this compound are yet to be shown. This study aimed to examine the potential of PLTM to prevent diabetic nephropathy in streptozotocin-induced diabetic rats and to examine the possible mechanisms of protection. Non-diabetic and STZ-diabetic male rats were treated orally by gavage with either the vehicle or with PTLM (200 mg/kg; twice/week) for 12 weeks. PTLM significantly increased urine volume and prevented glomerular and tubular damage and vacuolization in STZ-diabetic rats. It also increased creatinine excretion and reduced urinary albumin levels and the renal levels of kidney injury molecule-1 (KIM-1), 8-hydroxy-2'-deoxyguanosine (8-OHdG), neutrophil gelatinase-associated lipocalin (NGAL), and nephrin in the diabetic rats. PTLM also prevented an increase in the nuclear levels of NF-κβ, as well as the total levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), caspase-3, and Bax in the kidneys of diabetic rats. These effects were associated with reduced serum levels of triglycerides, cholesterol, and low-density lipoprotein cholesterol. In both the control and diabetic rats, PTLM significantly reduced fasting plasma glucose and enhanced the renal mRNA and cytoplasmic levels of Nrf2, as well as the levels of Bcl2, superoxide dismutase (SOD), and glutathione (GSH). However, PTLM failed to alter the cytoplasmic levels of keap1 in diabetic rats. In conclusion, PTLM prevents renal damage and dysfunction in STZ-diabetic rats through its hypoglycemic and hypolipidemic activities, as well as through its antioxidant potential, which is mediated by activating the Nrf2/antioxidant axis.

Glucotoxicity is mediated by cytoplasmic distribution of RAP1 in pancreatic β-cells

Diabetes mellitus (DM) is a group of chronic metabolic disorders characterized by persistent hyperglycemia. In our study, we analyzed the level and location of RAP1 changes in the development of β-cell dysfunction induced by glucotoxicity. We employed three pancreatic β-cell lines, namely INS-1, 1.2B4, and NIT-1, as well as a streptozotocin-induced diabetes rat model. We demonstrate that after high glucose treatment, RAP1 is increased, probably through induction by AKT, allowing RAP1 to shuttle from the nucleus to the cytoplasm and activate NF-κB signaling. Furthermore, non-enzymatic post-translational modifications of RAP1, such as advanced glycation end products and carbonylation may affect the function of RAP1, such as activation of the NF-κB signaling. Taken together, we showed that RAP1 is a new player in the mechanism of glucotoxicity in pancreatic β-cells.

MicroRNA-503-5p protects streptozotocin-induced erectile dysfunction in diabetic rats by downregulating SYDE2.

Plentiful studies have clarified miRNAs take on a key role in the sexual dysfunction of diabetic rats. This study aimed to figure out microRNA (miR)-503-5p/SYDE2 axis' latent mechanisms in streptozotocin-induced diabetic rat sexual dysfunction. A model of erectile dysfunction (ED) in diabetic rats was established by injecting streptozotocin. MiR-503-5p and SYDE2 in ED rats were altered by injection of miR-503-5p mimic or si/oe-SYDE2. The targeting link between miR-503-5p and SYDE2 was testified. ICP/MAP value was tested by pressure sensor; Penile capillary abundance was assessed; Penile cGMP and AGEs were detected; penile smooth muscle cell apoptosis was assessed; MiR-503-5p and SYDE2 were tested. In streptozotocin-induced ED rats, miR-503-5p was reduced and SYDE2 was elevated. Elevating miR-503-5p or silencing of SYDE2 can enhance penile erection rate, ICP/MAP value, capillary abundance, and cGMP but reduce AGEs and penile smooth muscle cell apoptosis rate in ED rats. Strengthening SYDE2 with elevating miR-503-5p turned around the accelerating effect of elevated miR-503-5p on penile erection in ED rats. SYDE2 was a downstream target gene of miR-503-5p. MiR-503-5p protects streptozotocin-induced sexual dysfunction in diabetic rats by targeting SYDE2.

Leaf extracts of Euclea natalensis A.D.C ameliorate biochemical abnormalities in high-fat-low streptozotocin-induced diabetic rats through modulation of the AMPK-GLUT4 pathway

ABSTRACT Euclea natalensis is a commonly used plant in traditional African medicine for treating several diseases, including diabetes. The objective of the present study was to evaluate the antidiabetic effects of the leaf extracts of Euclea natalensis and elucidate some of its mechanisms of action. High-fat diet – low Streptozotocin-induced diabetic Sprague Dawley rats were orally treated with the methanol and dichloromethane extracts (100 and 200 mg/kg bw), and their fasting blood glucose levels, body weights, and food and water intake were measured every seven days for 21 days. Biomarkers of oxidative stress, lipid profile, gluconeogenic enzyme activities, glucose transporter 4 (GLUT 4) protein expression, and AMP-activated protein kinase (AMPK) gene expression were also determined. The 200 mg/kg bw of methanol extracts significantly reduced fasting plasma glucose, glycated hemoglobin (HbAc1), triglycerides, and low-density lipoprotein levels. The extract increased insulin sensitivity and hepatic glycogen synthesis, decreased hepatic glucose output, and increased the activities of antioxidant enzymes in diabetic animals after 21 days of treatment. The methanol extract also significantly upregulated the relative expression of GLUT 4 protein via the promoted expression of skeletal muscle and hepatic AMPK. Histological investigation showed ameliorated pancreatic degeneration and expedited regeneration of islets of Langerhans in diabetic rats treated with the methanol extract compared with the dichloromethane extract. The findings demonstrated that Euclea natalensis has beneficial effects on the biochemical and cell abnormalities of type 2 diabetes, partly via the modulation of the AMPK – GLUT 4 pathway.

The Protective Effects of Vanillic Acid and Vanillic Acid-Coated Silver Nanoparticles (AgNPs) in Streptozotocin-Induced Diabetic Rats.

The production of nanoparticles enhances the bioactivity of biological molecules for drug delivery to diseased sites. This study explains how silver nanoparticle (AgNP) coating enhanced the protection effects of vanillic acid in male diabetic rats with streptozotocin- (STZ-) induced diabetes. Twenty-four rats were divided into four groups (n = 6) for this investigation. The first group (G1) is untreated, whereas diabetes was induced in the other three groups through STZ injection. Diabetic rats that were not getting therapy were included in the second group (G2, STZ-positive), whereas the other diabetic rats were divided into the third group (G3, vanillic acid-treated) and the fourth group (G4, vanillic acid-coated AgNPs treated). The treatment lasted four weeks. In G2, the induction of diabetes significantly (at P = 0.05) increased in serum glucose, glycated proteins, renal indices, interleukin-6 (IL-6), K+, immunoglobulins, and lipid peroxidation, while decreased Ca++, Na+, and other antioxidants in the kidney tissue homogenate. In addition, pathological altered signs were present in the pancreas and kidneys of diabetic rats. The renal and pancreatic tissues were effectively enhanced by vanillic acid or vanillic acid-coated AgNPs, bringing them very close to their prediabetic conditions. Vanillic acid-coated AgNPs offered a stronger defense against STZ-induced diabetes and lessened the effects of hyperglycemia compared to ordinary vanillic acid. Additionally, using vanillic acid coated with silver nanoparticles greatly increased the antioxidant and antidiabetic activity and reduced inflammation when compared to using vanillic acid alone.

Assessment of Cyperus articulatus for Antidiabetic Effects in a Streptozotocin-Induced Diabetic Rat Model

Assessment of Cyperus articulatus for Antidiabetic Effects in a Streptozotocin-Induced Diabetic Rat Model

Hepatic and renal effects of oral stingless bee honey in a streptozotocin-induced diabetic rat model.

Diabetes is known damage the liver and kidney, leading to hepatic dysfunction and kidney failure. Honey is believed to help in lowering the blood glucose levels of diabetic patients and reducing diabetic complications. However, the effect of stingless bee honey (SBH) administration in relieving liver and kidney damage in diabetes has not been well-studied. To investigate the effect of SBH administration on the kidney and liver of streptozotocin-induced (STZ; 55 mg/kg) diabetic Sprague Dawley rats. The rats were grouped as follows (n = 6 per group): non-diabetic (ND), untreated diabetic (UNT), metformin-treated (MET), and SBH+metformin-treated (SBME) groups. After successful diabetic induction, ND and UNT rats were given normal saline, whereas the treatment groups received SBH (2.0 g/kg and/or metformin (250 mg/kg) for 12 d. Serum biochemical parameters and histological changes using hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were evaluated. On H&E and PAS staining, the ND group showed normal architecture and cellularity of Bowman's capsule and tubules, whereas the UNT and MET groups had an increased glomerular cellularity and thickened basement membrane. The SBH-treated group showed a decrease in hydropic changes and mild cellularity of the glomerulus vs the ND group based on H&E staining, but the two were similar on PAS staining. Likewise, the SBME-treated group had an increase in cellularity of the glomerulus on H&E staining, but it was comparable to the SBH and ND groups on PAS staining. UNT diabetic rats had tubular hydropic tubules, which were smaller than other groups. Reduced fatty vacuole formation and dilated blood sinusoids in liver tissue were seen in the SBH group. Conversely, the UNT group had high glucose levels, which subsequently increased MDA levels, ultimately leading to liver damage. SBH treatment reduced this damage, as evidenced by having the lowest fasting glucose, serum alanine transaminase, aspartate transaminase, and alkaline phosphatase levels compared to other groups, although the levels of liver enzymes were not statistically significant. The cellularity of the Bowman's capsule, as well as histological alteration of kidney tubules, glomerular membranes, and liver tissues in diabetic rats after oral SBH resembled those of ND rats. Therefore, SBH exhibited a protective hepatorenal effect in a diabetic rat model.

Nrf-2-dependent antioxidant and anti-inflammatory effects underlie the protective effect of esculeoside A against retinal damage in streptozotocin-induced diabetic rats

Esculeoside A (ESA) is a tomato-derived glycoside with antioxidant and anti-inflammatory properties. The protective effect of ESA against diabetic retinopathy is not well-investigated and was the core objective of this study. In addition, we tested if such protection involves the activation of Nrf2 signaling. Type 1 diabetes mellitus (T1DM) was induced in adult Wistar male rats by an intraperitoneal injection of streptozotocin (65 mg/kg). Non-diabetic and T1DM rats were divided into two subgroup groups given either the vehicle or ESA (100 mg)/kg. An additional T1DM group was given ESA (100 mg/kg) and an Nrf2 inhibitor (2 mg/kg) (n=8 rats/group). Treatments continued for 12 weeks. In this study, according to the histological features, ESA improved the structure of ganglionic cells and increased the number of cells of the inner nuclear and plexiform layers in the retinas of T1DM rats. Concomitantly, it reduced the retina levels of malondialdehyde (lipid peroxides), vascular endothelial growth factor, interleukin-6, tumor necrosis factor-α, Bax, and caspase-3. In the retinas of the control and diabetic rats, ESA boosted the levels of total glutathione, superoxide dismutase, heme-oxygenase-1, and Bcl2, reduced the mRNA levels of REDD1, and enhanced cytoplasmic and nuclear levels of Nrf2. However, ESA failed to alter the mRNA levels of Nrf2 and keap1, protein levels of keap1, plasma glucose, plasma insulin, serum triglycerides, cholesterol, and LDL-c in both the control and T1DM rats. In conclusion, ESA alleviates retinopathy in T1DM rats by suppressing REDD1-associated degradation and inhibiting the Nrf2/antioxidant axis.

Ocimum gratissimum L. leaf flavonoid-rich extracts reduced the expression of p53 and VCAM in streptozotocin-induced cardiomyopathy rats

BackgroundThis study aimed to investigate the potential cardioprotective effects of flavonoid-rich extracts from Ocimum gratissimum leaves in a streptozotocin-induced diabetic rat model by assessing redox stress biomarkers, ATPase activities, gene expression levels, enzyme activities, and histopathological changes. MethodsDiabetic rats were administered low (LDOGFL) and high (HDOGFL) doses of O. gratissimum leaf flavonoid-rich extracts, metformin (MET), or served as diabetic (DC) and normal (NC) controls for twenty-one days. Various cardiac parameters were evaluated, including redox stress biomarkers, ATPase activities, relative gene expression of p53 and VCAM, phosphatase activities, transaminase activities, serum creatine kinase-MB (CKMB) activities, cardiac troponin levels, and natriuretic peptide levels. Additionally, heart histoarchitecture was also examined using hematoxylin and eosin (H&E) staining. ResultsFlavonoid-rich extracts of O. gratissimum significantly (p < 0.05) mitigated redox stress by decreasing malondialdehyde (MDA) levels and increasing reduced glutathione (GSH), glutathione-S-transferase (GST), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities in diabetic treated rats. The extracts also notably (p < 0.05) improved ATPase activities and significantly (p < 0.05) modulated the relative gene expression of p53 and VCAM in diabetic treated rats. Furthermore, diabetic rat administered flavonoid-rich extracts markedly (p < 0.05) attenuated phosphatase activities, transaminase activities, CKMB activities, cardiac troponin levels, and natriuretic peptide levels. Histopathological examination of the diabetic rats revealed improved cardiac histoarchitecture in extract-treated groups compared to diabetic controls. ConclusionThese findings suggest that O. gratissimum leaf flavonoid-rich extracts confer cardioprotective effects in STZ-induced diabetic rats by ameliorating redox imbalance, modulating gene expression, regulating enzyme activities, and preserving cardiac histoarchitecture. These results highlight the potential therapeutic application of O. gratissimum flavonoids in managing diabetes-induced cardiomyopathy.

Diabetes and high-glucose could upregulate the expression of receptor for activated C kinase 1 in retina.

Diabetic retinopathy (DR) is a major ocular complication of diabetes mellitus, leading to visual impairment. Retinal pigment epithelium (RPE) injury is a key component of the outer blood retinal barrier, and its damage is an important indicator of DR. Receptor for activated C kinase 1 (RACK1) activates protein kinase C-ε (PKC-ε) to promote the generation of reactive oxygen species (ROS) in RPE cells, leading to apoptosis. Therefore, we hypothesize that the activation of RACK1 under hypoxic/high-glucose conditions may promote RPE cell apoptosis by modulating PKC-ε/ROS, thereby disrupting the barrier effect of the outer blood retinal barrier and contributing to the progression of DR. To investigate the role and associated underlying mechanisms of RACK1 in the development of early DR. In this study, Sprague-Dawley rats and adult RPE cell line-19 (ARPE-19) cells were used as in vivo and in vitro models, respectively, to explore the role of RACK1 in mediating PKC-ε in early DR. Furthermore, the impact of RACK1 on apoptosis and barrier function of RPE cells was also investigated in the former model. Streptozotocin-induced diabetic rats showed increased apoptosis and up-regulated expression of RACK1 and PKC-ε proteins in RPE cells following a prolonged modeling. Similarly, ARPE-19 cells exposed to high glucose and hypoxia displayed elevated mRNA and protein levels of RACK1 and PKC-ε, accompanied by an increases in ROS production, apoptosis rate, and monolayer permeability. However, silencing RACK1 significantly downregulated the expression of PKC-ε and ROS, reduced cell apoptosis and permeability, and protected barrier function. RACK1 plays a significant role in the development of early DR and might serve as a potential therapeutic target for DR by regulating RPE apoptosis and barrier function.

Exercise May Increase Oxidative Stress in the Sciatic Nerve in Streptozotocin-Induced Diabetic Rats.

Background and Objectives: Diabetic peripheral neuropathy (DPN) affects approximately half of patients with diabetes mellitus (DM), contributing to falls and fractures. Oxidative stress, which is linked to DM-induced hyperglycemia, has been implicated in the onset of DPN. Although exercise is recommended for patients with DM, its effect on DPN remains unclear. Therefore, this study aimed to investigate the effect of exercise on DPN and the mechanisms involved. Material and Methods: Thirty male Wistar rats were divided into control, streptozotocin (STZ)-induced diabetic (DM), and STZ-induced diabetic/exercise (DM + Ex) groups. Diabetes was induced using STZ injection. Rats in the DM + Ex groups underwent six weeks of treadmill exercise. Sciatic nerve parameters, which included motor nerve conduction velocity (MNCV), antioxidant enzymes (catalase, glutathione peroxidase [GPx], and superoxide dismutase [SOD]), oxidative stress markers (malondialdehyde [MDA] and 4-hydroxy-2-nonenal [4HNE]), and neurotrophic factors (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]), were examined. Results: Exercise alleviated DM-induced decreases in MNCV in rats. Although exercise did not significantly affect antioxidant enzyme activity, 4HNE levels increased significantly, indicating increased oxidative stress. Additionally, exercise did not significantly affect DM-induced increases in NGF and BDNF levels in rats. Conclusions: Exercise may prevent DPN in rats with DM, possibly through nonantioxidant mechanisms.

Quercetin improves diabetic kidney disease by inhibiting ferroptosis and regulating the Nrf2 in streptozotocin-induced diabetic rats

Diabetic kidney disease (DKD) is a leading factor in end-stage renal disease. The complexity of its pathogenesis, combined with the limited treatment efficacy, necessitates deeper insights into potential causes. Studies suggest that ferroptosis-driven renal tubular damage contributes to DKD's progression, making its counteraction a potential therapeutic strategy. Quercetin, a flavonoid found in numerous fruits and vegetables, has demonstrated DKD mitigation in mouse models, though its protective mechanism remains ambiguous. In this study, we delved into quercetin’s potential anti-ferroptotic properties, employing a DKD rat model and high glucose (HG)-treated renal tubular epithelial cell models. Our findings revealed that HG prompted unusual ferroptosis activation in renal tubular epithelial cells. However, quercetin counteracted this by inhibiting ferroptosis and activating NFE2-related factor 2 (Nrf2) expression in both DKD rats and HG-treated HK-2 cells, indicating its renal protective role. Further experiments, both in vivo and in vitro, validated that quercetin stimulates Nrf2. Thus, our research underscores quercetin’s potential in DKD treatment by modulating the ferroptosis process via activating Nrf2 in a distinct DKD rat model, offering a fresh perspective on quercetin’s protective mechanisms.