Autophagy enhances the differentiation of insulin-producing cells from Wharton's jelly-derived mesenchymal stem cells.

Autophagy disruption suppresses insulin production and induces diabetes. The role of autophagy in the differentiation of Wharton's jelly (WJ)-derived mesenchymal stem cells (WJSCs) into insulin-producing cells (IPCs) was investigated in this experimental study. The WJSCs were incubated in a differentiation medium (DM) with or without an autophagy inhibitor (3-methyladenine: 3MA). The differentiation of IPCs was confirmed by flow cytometry analysis of PDX-1 and insulin-positive cells, insulin secretion, and the high expression of ß cell-specific genes, Glucose transporter 2 (GLUT-2), and INSULIN. Autophagy has been assessed by calculating the percentage of Acridine orange (AO)-positive cells, expression of autophagy-related genes, and the LC3B/LC3A ratio. ß cell-specific genes were up-regulated in the DM group, and 3MA decreased their expression. In the DM+3MA-treated cells, the expression of GLUT-2 and INSULIN genes and insulin secretion decreased compared to the DM group. In cells treated with 3MA, there was a significant decrease in the percentage of PDX-1 and insulin-positive cells compared to 3MA-untreated cells. Additionally, in the group receiving both DM and 3MA treatment, the expression of autophagy-related genes, the LC3B/LC3A protein ratio, and the percentage of AO-stained cells were significantly reduced compared to the group receiving only DM treatment. These findings suggest autophagy is essential for ß cell differentiation and insulin secretion.

Thymoquinone effects on autophagy, apoptosis, and oxidative stress in cisplatin-induced testicular damage in mice.

PURPOSE: In this study, the effect of thymoquinone (TQ) on CP-induced spermatogenesis defects in mice has been investigated. METHODS: Sperm parameters, serum testosterone concentration, histology, Bax/Bcl-2 ratio, and expression of autophagy-related biomarkers have been assessed. Total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) in testicular tissue were examined for the evaluation of oxidative stress levels. RESULTS: CP has induced histological changes and significantly increased the Bax/Bcl-2 ratio, decreased testosterone concentration, testicular weight, and sperm quality. CP induced oxidative stress by elevating OSI in the testicular tissue (p < 0.05). Expression of the autophagy-inducer genes (ATG7, ATG5, and Beclin-1) and ratio of LC3B/LC3A proteins were significantly decreased, while mTOR expression was increased in the CP group. TQ pretreatment dose-dependently decreased the Bax/Bcl-2 ratio and mTOR gene expression while increasing the expression of ATG5 and ATG7 genes, LC3B/LC3A ratio, and Beclin-1 proteins. TQ could also dose-dependently reverse the histology, testosterone level, and sperm quality of the CP-intoxicated mice. CONCLUSIONS: These findings show that TQ pretreatment can enhance sperm production by inducing autophagy and reducing apoptosis and oxidative stress in the CP-intoxicated mouse testicles.

The Protective Effects of Syringic Acid on Bisphenol A-Induced Neurotoxicity Possibly Through AMPK/PGC-1α/Fndc5 and CREB/BDNF Signaling Pathways.

Bisphenol A (BPA), an endocrine disruptor, is commonly used to produce epoxy resins and polycarbonate plastics. Continuous exposure to BPA may contribute to the development of diseases in humans and seriously affect their health. Previous research suggests a significant relationship between the increased incidence of neurological diseases and the level of BPA in the living environment. Syringic acid (SA), a natural derivative of gallic acid, has recently considered much attention due to neuromodulator activity and its anti-oxidant, anti-apoptotic, and anti-inflammatory effects. Therefore, in this study, we aimed to investigate the effects of SA on oxidative stress, apoptosis, memory and locomotor disorders, and mitochondrial function, and to identify the mechanisms related to Alzheimer's disease (AD) in the brain of rats receiving high doses of BPA. For this purpose, male Wistar rats received BPA (50, 100, and 200 mg/kg) and SA (50 mg/kg) for 21 days. The results showed that BPA exposure significantly altered the rats' neurobehavioral responses. Additionally, BPA, by increasing the level of ROS, and MDA level, increased the level of oxidative stress while reducing the level of antioxidant enzymes, such as SOD, CAT, GPx, and mitochondrial GSH. The administration of BPA at 200 mg/kg significantly decreased the expression of ERRα, TFAM, irisin, PGC-1α, Bcl-2, and FNDC5, while it increased the expression of TrkB, cytochrome C, caspase 3, and Bax. Moreover, the Western blotting results showed that BPA increased the levels of P-AMPK, GSK3b, p-tau, and Aß, while it decreased the levels of PKA, P-PKA, Akt, BDNF, CREB, P-CREB, and PI3K. Meanwhile, SA at 50 mg/kg reversed the behavioral, biochemical, and molecular changes induced by high doses of BPA. Overall, BPA could lead to the development of AD by affecting the mitochondria-dependent apoptosis pathway, as well as AMPK/PGC-1α/FNDC5 and CREB/BDNF/TrkB signaling pathways, and finally, by increasing the expression of tau and Aß proteins. In conclusion, SA, as an antioxidant, significantly reduced the toxicity of BPA.

Adipose-Derived Stem Cells' Secretome Attenuates Lesion Size and Parasite Loading in Leishmaniasis Caused by Leishmania Major in Mice.

Background: Stem cell-derived secretome (SE) released into the extracellular space contributes to tissue repair. The present study aimed to investigate the impact of isolated secretome (SE) from adipose-derived mesenchymal stem cells (ASCs) on Leishmania major (L. major) lesions in BALB/c mice. Methods: This experimental study was conducted at Ahvaz University of Medical Sciences (Ahvaz, Iran) in 2021. Forty female BALB/c mice were infected with stationary phase promastigotes through intradermal injection in the bottom of their tail and randomly divided into four groups (n=10 per group). The mice were given SE (20 mg/mL), either alone or in combination with Glucantime (GC, 20 mg/mL/Kg), meglumine antimoniate (20 mg/mL/Kg) for the GC group, and phosphate-buffered saline (PBS) for the control group. After eight weeks, the lesion size, histopathology, the levels of Interleukin 10 (IL-10), and Interleukin 12 (IL-12) were assessed. For the comparison of values between groups, the parametric one-way ANOVA was used to assess statistical significance. Results: At the end of the experiment, the mice that received SE had smaller lesions (4.56±0.83 mm versus 3.62±0.59 mm, P=0.092), lower levels of IL-10 (66.5±9.7 pg/mL versus 285.4±25.2 pg/mL, P<0.001), and higher levels of IL-12 (152.2±14.2 pg/mL versus 24.2±4.4 pg/mL, P<0.001) than the control. Histopathology findings revealed that mice treated with SE had a lower parasite burden in lesions and spleen than the control group. Conclusion: The current study demonstrated that ADSC-derived SE could protect mice infected with L. major against leishmaniasis.

Quercetin-loaded solid lipid nanoparticles exhibit antitumor activity and suppress the proliferation of triple-negative MDA-MB 231 breast cancer cells: implications for invasive breast cancer treatment.

BACKGROUND: Quercetin (QC) is a naturally occurring flavonoid found in abundance in fruits and vegetables. Its anti-cancer and anti-inflammatory properties have been previously demonstrated, but its low bioavailability hampers its clinical use. Triple-negative breast cancer is a subtype of breast cancer with a poor response to chemotherapy. This study investigates the anti-cancer effects of quercetin-solid lipid nanoparticles (QC-SLN) on the triple-negative breast cancer cell line MDA-MB231. MATERIALS AND METHODS: MCF-7 and MDA-MB231 cells were treated with 18.9 µM of QC and QC-SLN for 48 h. Cell viability, apoptosis, colony formation assay, and the anti-angiogenic effects of the treatment were evaluated. RESULTS: QC-SLN displayed optimal properties (particle size of 154 nm, zeta potential of -27.7 mV, encapsulation efficiency of 99.6%, and drug loading of 1.81%) and exhibited sustained release of QC over 72 h. Compared to the QC group, the QC-SLN group showed a significant decrease in cell viability, colony formation, angiogenesis, and a substantial increase in apoptosis through the modulation of Bax and Bcl-2 at both gene and protein levels. The augmentation in the proportion of cleaved-to-pro caspases 3 and 9, as well as poly (ADP-ribose) polymerase (PARP), under the influence of QC-SLN, was conspicuously observed in both cancer cell lines. CONCLUSIONS: This study showcases quercetin-solid lipid nanoparticles (QC-SLN) as a promising therapy for triple-negative breast cancer. The optimized QC-SLN formulation improved physicochemical properties and sustained quercetin release, resulting in reduced cell viability, colony formation, angiogenesis, and increased apoptosis in the MDA-MB231 cell line. These effects were driven by modulating Bax and Bcl-2 expression, activating caspases 3 and 9, and poly (ADP-ribose) polymerase (PARP). Further in vivo studies are needed to confirm QC-SLN's efficacy and safety.

Possible mechanisms involved in the neuroprotective effects of chrysin against mild traumatic brain injury-induced spatial cognitive decline: An in vivo study in a rat model.

Traumatic brain injury (TBI) is recognized as an important risk factor for cognitive deficits. The present study was designed to determine the potential neuroprotective effects of chrysin, a natural flavonoid compound, against TBI-induced spatial cognitive decline and the possible mechanisms involved. Oral administration of chrysin (25, 50, or 100 mg/kg/day) was initiated in rats immediately following the induction of the diffuse TBI model using the weight-dropping Marmarou model. Spatial cognitive ability, hippocampal synaptic plasticity, blood-brain barrier (BBB) permeability, brain water content, and histological changes were assessed at scheduled time points. The animals subjected to TBI exhibited spatial cognitive decline in the Morris water maze (MWM) test, which was accompanied by inhibition of hippocampal long-term potentiation (LTP) induction at the perforant path-dentate gyrus (PP-DG) synapses. Additionally, TBI caused BBB disruption, brain edema, and neuronal loss. Interestingly, treatment with chrysin (especially in the dose of 100 mg/kg) alleviated all the above-mentioned neuropathological changes related to TBI. The results provide evidence that chrysin improves TBI-induced spatial cognitive decline, which may be partly related to the amelioration of hippocampal synaptic dysfunction, alleviation of BBB disruption, reduction of brain edema, and prevention of neuronal loss.

Hepatoprotective and anti-hyperglycemic effects of ferulic acid in arsenic-exposed mice.

Arsenic is a toxic metalloid that increases the risk of hepatotoxicity and hyperglycemia. The objective of the present study was to assess the effect of ferulic acid (FA) in mitigating glucose intolerance and hepatotoxicity caused by sodium arsenite (SA). A total of six groups including control, FA 100 mg/kg, SA 10 mg/kg, and groups that received different doses of FA (10, 30, and 100 mg/kg), respectively just before SA (10 mg/kg) for 28 days were examined. Fasting blood sugar (FBS) and glucose tolerance tests were conducted on the 29th day. On day 30, mice were sacrificed and blood and tissues (liver and pancreas) were collected for further investigations. FA reduced FBS and improved glucose intolerance. Liver function and histopathological studies confirmed that FA preserved the structure of the liver in groups received SA. Furthermore, FA increased antioxidant defense and decreased lipid peroxidation and tumor necrosis factor-alpha level in SA-treated mice. FA, at the doses of 30 and 100 mg/kg, prevented the decrease in the expression of PPAR-γ and GLUT2 proteins in the liver of mice exposed to SA. In conclusion, FA prevented SA-induced glucose intolerance and hepatotoxicity by reducing oxidative stress, inflammation, and hepatic overexpression of PPAR-γ and GLUT2 proteins.

Effective inhibition of breast cancer stem cell properties by quercetin-loaded solid lipid nanoparticles via reduction of Smad2/Smad3 phosphorylation and ß-catenin signaling pathway in triple-negative breast cancer.

BACKGROUND: The presence of cancer stem cells (CSCs) is a major cause of resistance to cancer therapy and recurrence. Triple-negative breast cancer (TNBC) is a subtype that responds poorly to therapy, making it a significant global health issue. Quercetin (QC) has been shown to affect CSC viability, but its low bioavailability limits its clinical use. This study aims to increase the effectiveness of QC in inhibiting CSC generation by using solid lipid nanoparticles (SLNs) in MDA-MB231 cells. MATERIALS AND METHODS: After treating MCF-7 and MDA-MB231 cells with 18.9 µM and 13.4 µM of QC and QC-SLN for 48 h, respectively, cell viability, migration, sphere formation, protein expression of ß-catenin, p-Smad 2 and 3, and gene expression of EMT and CSC markers were evaluated. RESULTS: The QC-SLN with particle size of 154 nm, zeta potential of -27.7 mV, and encapsulation efficacy of 99.6% was found to be the most effective. Compared to QC, QC-SLN significantly reduced cell viability, migration, sphere formation, protein expression of ß-catenin and p-Smad 2 and 3, and gene expression of CD44, zinc finger E-box binding homeobox 1 (ZEB1), vimentin, while increasing the gene expression of E-cadherin. CONCLUSIONS: Our findings demonstrate that SLNs improve the cytotoxic effect of QC in MDA-MB231 cells by increasing its bioavailability and inhibiting epithelial-mesenchymal transition (EMT), thereby effectively inhibiting CSC generation. Therefore, SLNs could be a promising new treatment for TNBC, but more in vivo studies are needed to confirm their efficacy.

Gentisic acid ameliorates type 2 diabetes induced by Nicotinamide-Streptozotocin in male mice by attenuating pancreatic oxidative stress and inflammation through modulation of Nrf2 and NF-кB pathways.

AIMS: There is a close link between oxidative stress, inflammation, and type 2 diabetes mellitus (T2DM). Gentisic acid (GA) is a di-phenolic compound and an active metabolite of aspirin that possesses antioxidant and anti-inflammatory properties, but its potential anti-diabetic effects have not been evaluated so far. Therefore, this study aimed to evaluate GA's potential antidiabetic effects through the Nuclear Factor Erythroid 2-Related Factor (Nrf2) and Nuclear Factor Kappa Beta (NF-кB) signaling pathways. MATERIAL AND METHODS: In this study, T2DM induced by a single intraperitoneal injection of STZ (65 mg/kg B.W) after 15 min nicotinamide (120 mg/kg B.W) injection. After seven days of injections, fasting blood glucose (FBS) was measured. Seven days after FBS monitoring treatments started. Grouping and treatments were as follows: 1) Normal control group; NC, 2) Diabetic control group; DC, 3) Metformin group; MT (150 mg/kg B.W, daily), 4) Test group; GA (100 mg/kg B.W, daily). Treatments continued for 14 consecutive days. KEY FINDINGS: Diabetic mice treatment with GA significantly decreased FBS, improved plasma lipid profiles and pancreatic antioxidant status. GA modulated Nrf2 pathway by upregulation of Nrf2 protein, NAD(P)H: quinone oxidoreductase 1 (Nqo1), and p21, and downregulation of miR-200a, Kelch-like ECH-associated protein 1 (Keap1), and nicotinamide adenine dinucleotide phosphate oxidase-2 (NOX2). Also, GA attenuated inflammation by upregulation of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and interleukin-10 (IL-10) and downregulation of miR-125b, NF-кB, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß). SIGNIFICANCE: GA attenuates T2DM, possibly by improving antioxidant status through the Nrf2 pathway and attenuation of inflammation.

The protective effect of p-Coumaric acid on hepatic injury caused by particulate matter in the rat and determining the role of long noncoding RNAs MEG3 and HOTAIR.

Increasing air pollution is associated with serious human health problems. P-coumaric acid (PC) is a herbal phenolic compound that exhibits beneficial pharmacological potentials. Here, the protective effect of PC on liver injury induced by air pollution was examined. Thirty-two adult male Wistar rats (200-250 g) were divided randomly into four groups (n = 8). The groups were; Control (rats received DMSO and then exposed to clean air), PC (rats received PC and then exposed to clean air), DMSO + Dust (rats received DMSO and then exposed to dust), and PC + Dust (the animals received PC and then exposed to dust). The clean air, DMSO, PC, and dust were administrated 3 days a week for 6 consecutive weeks. The rats were anesthetized and their blood samples and liver sections were taken to conduct molecular, biomedical, and histopathological tests. Dust exposure increased the liver enzymes, bilirubin, triglyceride, cholesterol, and the production of liver malondialdehyde, and decreased in liver total anti-oxidant capacity and serum high-density lipoprotein. It also increased the mRNA expression of inflammatory-related cytokines, decreased the mRNA expression of SIRT-1, decreased the expression levels of miR-20b5p, and MEG3 while increased the expression levels of miR-34a, and HOTAIR. Dust exposure also increased the liver content of three cytokines TNF-α, NF-κB, HMGB-1, and ATG-7 proteins. PC enhanced liver function against adverse effects of dust through recovering almost all the studied variables. Exposure to dust damaged the liver through induction of oxidative stress, inflammation, and autophagy. PC protected the liver against dust-induced cytotoxicity.

Citicoline ameliorates arsenic-induced hepatotoxicity and diabetes in mice by overexpression of VAMP2, PPAR-γ, As3MT, and SIRT3.

The use of arsenic in arsenic-based pesticides has been common in many countries in the past and today. There is considerable evidence linking arsenic exposure to hepatotoxicity and diabetes. Destructive phenomena such as hepatic oxidative stress and inflammation can interfere with glucose uptake and insulin function. In the present study, the antioxidant, anti-inflammatory, and molecular mechanism of citicoline against sodium arsenite-induced hepatotoxicity and glucose intolerance were investigated in mice. Citicoline improved glucose tolerance impaired by sodium arsenite. Citicoline increased the hepatic activity of catalase, superoxide dismutase, and glutathione peroxidase enzymes. Moreover, we found that citicoline prevents an increase in the levels of thiobarbituric acid reactive substances. Citicoline reduced levels of caspase 3, tumor necrosis factor-alpha, and interleukin 6 in sodium arsenite intoxicated groups. It was shown that citicoline increased the expression of arsenite methyltransferase, vesicle-associated membrane protein 2, peroxisome proliferator-activated receptor gamma, and sirtuin 3 to combat sodium arsenite toxicity. Citicoline reduced glucose intolerance, which was disrupted by sodium arsenite, by affecting the pancreatic and extra-pancreatic pathways involved in insulin production, secretion, and action. Based on our results, citicoline can be considered a modulating agent against arsenic-induced hepatotoxicity and hyperglycemia. Considering the relationship between arsenic exposure and the occurrence of side effects such as liver toxicity and diabetes, it is necessary to monitor and awareness of arsenic residues from sources such as drinking water.

Gentisic acid protects against diabetic nephropathy in Nicotinamide-Streptozotocin administered male mice by attenuating oxidative stress and inflammation: The role of miR-200a/Keap1/Nrf2 pathway, renin-angiotensin system (RAS) and NF-кB.

Oxidative stress and inflammation play a pivotal role in the pathogenesis of diabetic nephropathy (DN). Local renin-angiotensin systems (RAS) contribute to the pathogenesis and progression of DN by exacerbating oxidative stress and inflammation.Gentisic acid (GA), a phenolic compound and also a metabolite of aspirin, is reported to possess antioxidant and anti-inflammatory properties. However, the protective effects of GA against DN remain to be elucidated. Nicotinamide (120 mg/kg) and streptozotocin (65 mg/kg) were used to induce diabetes in male mice. Oral administration of GA once daily for 2 weeks (100 mg/kg) ameliorated diabetes-induced renal injury by reducing plasma creatinine, urea, blood urea nitrogen, and urinary albuminuria levels. Diabetic mice showed a significant increase in total oxidant status and malondialdehyde, along with decreased catalase, superoxide dismutase, and glutathione peroxidase in the kidney tissue, which was ameliorated in the GA-treated mice. Histopathological analysis showed that GA treatment reduced diabetes-induced renal injury. Furthermore, GA treatment was associated with the downregulation of miR-125b, nuclear factor kappa beta (NF-кB), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and upregulation of interleukin-10 (IL-10), miR-200a, and nuclear factor erythroid 2-related factor 2 (Nrf2) in the renal tissue. GA treatment also downregulated angiotensin-converting enzyme 1 (ACE1), angiotensin II receptor 1 (AT1R), and NADPH oxidase 2 (NOX 2) and upregulated angiotensin-converting enzyme 2 (ACE2). In conclusion, the ameliorative effects of GA against DN may be attributed to its powerful antioxidant and anti-inflammatory properties through the downregulation of NF-кB, upregulation of Nrf2, and modulation of RAS in renal tissue.

Therapeutic Utilization of Zinc Supplementation Concurrent with Ozone Therapy Ameliorates Diabetic Foot Ulcer and Attenuates Serum Level of C-reactive Protein- A Case Report Study.

Non-healing diabetic foot ulcer (DFU) is one of the main complications in diabetic patients. This case reported a 65-year-old male with a neuropathic ulcer in the right foot came to Ahwaz Wound Clinic after the wound had not healed with routine treatments. In addition to the routine treatment program, we used tropical ozone therapy and autohemotherapy (blood ozone therapy) for 2 months. Zinc supplementation (50 mg) was also administered daily during the treatment. The DFU was clearly healed with diminishing inflammation and wound closing, and there were no side effects. Additionally, the C-reactive protein level was obviously decreased during the treatment indicating effective suppression of infection. This way indicates a helpful new intervention approach to the treatment of DFU.

Gemfibrozil palliates adriamycin-induced testicular injury in male rats via modulating oxidative, endocrine and inflammatory changes in rats.

Adriamycin (ADR), an antineoplastic drug, is widely used to treat different types of cancers. Yet, the usage is limited because of its severe side effects on testis. On the other hand, gemfibrozil (GEM), as an anti-hyperlipidemic drug, has other pharmacological effects independent of lipid- lowering activity including anti-inflammatory and antioxidant properties. The present experiment was designed to investigate the effect of GEM on ADR-induced testicular injury in male rats. A total of 28 male Wistar rats were divided into 4 equal groups: Control; ADR; ADR + GEM; GEM. Serum level of testosterone, luteinizing hormone and follicle stimulating hormone were assessed. Also, testicular tissue oxidant/antioxidant markers (malondialdehyde, total antioxidant capacity, nitric oxide, superoxide dismutase, catalase, glutathione peroxidase and glutathione) and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1ß) were measured. Histopathological studies were conducted on testes. GEM improved hormonal profile and antioxidant defenses in comparison with ADR-treated animals. GEM, significantly reduced the production of proinflammatory cytokines compared with ADR-treated animals. Hormonal and biochemical results were further supported by testicular histopathological findings. Thus, GEM might represent a promising therapeutic modality for the attenuation of testicular injury induced by ADR in clinic.

p-Coumaric acid has pure anti-inflammatory characteristics against hepatopathy caused by ischemia-reperfusion in the liver and dust exposure.

Objectives: Studies show that chronic injuries like air pollution or acute damage such as hepatic ischemia-reperfusion (IR) cause various cellular pathologies such as oxidative stress, apoptosis, autophagy, and inflammation in hepatocytes. p-Coumaric acid (p-CA) is known as an antioxidant with many therapeutic impacts on inflammatory-related pathologies. In this experiment, we aimed to assess the hepatoprotective effects of p-CA on liver damage induced by dust and IR injury in adult male rats. Materials and Methods: Forty-eight adult male Wistar rats were divided into 6 groups; Control (CTRL); sham; DMSO+Dust+Laparotomy (LPT); DMSO+Dust+Ischemia-reperfusion (IR); p-CA+Dust+LPT; and p-CA+Dust+IR. Clean air, DMSO, p-CA, and dust were administrated 3 days a week for 6 consecutive weeks. Animals were sacrificed, the blood samples were aspirated and the liver sections were prepared for biochemical and histopathological assessments. Results: Significantly (P<0.05), the results represented that dust and IR can potentially increase the levels of ALT, AST, direct and total bilirubin, triglyceride, and cholesterol in serum. Also, MDA, TNF-α , NF-κB . HMGB-1 and ATG-7 levels were increased in hepatocytes. Gene expression of Nrf2, HOX-1, IL-6, HOTAIR, and miR-34a showed an incremental trend in the liver tissue. Total antioxidant capacity (TAC) in hepatocytes was decreased following dust exposure and IR induction. Also, miR-20b-5p, MEG3, and SIRT1 in the liver were decreased in dust and dust+IR groups. Conclusion: p-CA alleviated pathological changes caused by dust exposure and IR injury. p-CA protected hepatic injury induced by dust and IR by inhibition of oxidative injury, inflammation, and autophagy.

Diabetic nephropathy induced by methylglyoxal: gallic acid regulates kidney microRNAs and glyoxalase1-Nrf2 in male mice.

BACKGROUND: Methylglyoxal (MG) has been reported to be a toxic by-product of glycolysis and intracellular stressor compound. This study investigated the effects of gallic acid (GA) against diabetic nephropathy (DN) induced by MG in male mice. METHODS: DN was induced by methylglyoxal (600 mg/kg/day, p.o.) treated for 28 consecutive days. The animals received GA (30 mg/kg/day, p.o.) and metformin (MT) (150 mg/kg/day, p.o.) for 7 consecutive days after diabetes induction. Biochemical assays, antioxidant evaluation, microRNAs associated with fibrosis, endoplasmic reticulum stress, and histopathological analysis were examined. RESULTS: MG increased malondialdehyde, albuminuria, Nrf2, miR-192 and miR-204 expression in diabetic groups and GA decreased them. Superoxide dismutase, catalase, glyoxalase1, and miR-29a expression decreased in diabetic groups and increased in treatment with GA. CONCLUSION: Our results revealed that GA has improved DN induced by MG via amelioration of biochemical indices, histopathological aspects, oxidative stress and microRNAs associated with endoplasmic reticulum stress and fibrosis.