scholarly journals The Controversial Role of Folic Acid on Diabetic Auditory Neuropathy

2021 ◽  
Author(s):  
Aida Doostkam ◽  
Hossein Mirkhani ◽  
Kamyar Iravani ◽  
Saied Karbalay-Doust ◽  
Afsaneh Doosti ◽  
...  
Keyword(s):  
Folic Acid ◽  
Stria Vascularis ◽  
Diabetic Rats ◽  
Auditory Neuropathy ◽  
Spiral Ligament ◽  
Functional Disorders ◽  
Sprague Dawley ◽  
Auditory Brain Stem Response ◽  
Group 2

Abstract PurposeDiabetic auditory neuropathy(DAN) is a common complication of diabetes that seriously affects the quality of life in patients. In this study, we investigate the role of folic acid in the treatment of DAN in an experimental rat model.MethodsThirty-two Sprague-Dawley rats were equally divided into 4 groups: group 1, normal; group 2, diabetic rats; group 3and 4, rats treated with folic acid (40 and 80 mg/kg, respectively). The tools we used in this study to investigate the effect of folic acid on DAN were auditory brain stem response, stereology methodfor estimation ofthe volume and number ofspiral ganglion,volume of stria vascularis, and spiral ligament, and measurement of homocysteine (HCY), malondealdehyde(MDA) and superoxide dismutase.ResultsOur study showed that folic acid treatment was not significantly effective in improving structural and functional disorders in DAN, despite its effect in reducing HCY and MDA as oxidative biomarkers.ConclusionFolic acid is not effective in relieving morphological and functional disorders in DAN.

Mechanisms of hearing loss and cell death in the cochlea of connexin mutant mice

2020 ◽  
Vol 319 (3) ◽  
pp. C569-C578
Author(s):  
Bei Chen ◽  
Hongen Xu ◽  
Yanfang Mi ◽  
Wei Jiang ◽  
Dan Guo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Hair Cell ◽  
Stria Vascularis ◽  
Reactive Oxygen Species Generation ◽  
Cell Loss ◽  
Outer Hair Cells ◽  
Spiral Ligament ◽  
Hair Cell Loss ◽  
Auditory Brain Stem Response

Mutations in connexin 30 (Cx30) are known to cause severe congenital hearing impairment; however, the mechanism by which Cx30 mediates homeostasis of endocochlear gap junctions is unclear. We used a gene deletion mouse model to explore the mechanisms of Cx30 in preventing hearing loss. Our results suggest that despite severe loss of the auditory brain-stem response and endocochlear potential at postnatal day 18, Cx30−/− mice only show sporadic loss of the outer hair cells. This inconsistency in the time course and severity of hearing and hair cell losses in Cx30−/− mice might be explained, in part, by an increase in reactive oxygen species generation beginning at postnatal day 10. The expression of oxidative stress genes was increased in Cx30−/− mice in the stria vascularis, spiral ligament, and organ of Corti. Furthermore, Cx30 deficiency caused mitochondrial dysfunction at postnatal day 18, as assessed by decreased ATP levels and decreased expression of mitochondrial complex I proteins, especially in the stria vascularis. Proteomic analysis further identified 444 proteins that were dysregulated in Cx30−/− mice, including several that are involved in mitochondria electron transport, ATP synthesis, or ion transport. Additionally, proapoptotic proteins, including Bax, Bad, and caspase-3, were upregulated at postnatal day 18, providing a molecular basis to explain the loss of hearing that occurs before hair cell loss. Therefore, our results are consistent with an environment of oxidative stress and mitochondrial damage in the cochlea of Cx30−/− mice that is coincident with hearing loss but precedes hair cell loss.

scholarly journals A Comparison of Wound Healing Rate Following Treatment with Aftamed and Chlorine Dioxide Gels in Streptozotocin-Induced Diabetic Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Fouad Al-Bayaty ◽  
Mahmood Ameen Abdulla
Keyword(s):  
Wound Healing ◽  
Chlorine Dioxide ◽  
Cellular Proliferation ◽  
Radical Scavenging ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Thickness Skin ◽  
Group 2

Background and Purpose. This study aimed to evaluate the wound healing activities of Aftamed and chlorine dioxide gels in streptozotocin-induced diabetic rats. Experimental Approach. Forty-eight Sprague Dawley rats were chosen for this study, divided into 4 groups. Diabetes was induced. Two-centimeter-diameter full-thickness skin excision wounds were created. Animals were topically treated twice daily. Groups 1, the diabetic control group, were treated with 0.2 mL of sterile distilled water. Group 2 served as a reference standard were treated with 0.2 mL of Intrasite gel. Groups 3 and 4 were treated with 0.2 mL of Aftamed and 0.2 mL of chlorine dioxide gels respectively. Granulation tissue was excised on the 10th day and processed for histological and biochemical analysis. The glutathione peroxidase ,superoxide dismutase activities and the malondialdehyde (MDA) levels were determined. Results. Aftamed-treated wounds exhibited significant increases in hydroxyproline, cellular proliferation, the number of blood vessels, and the level of collagen synthesis. Aftamed induced an increase in the free radical-scavenging enzyme activity and significantly reduced the lipid peroxidation levels in the wounds as measured by the reduction in the MDA level. Conclusions. This study showed that Aftamed gel is able to significantly accelerate the process of wound healing in diabetic rats.

scholarly journals Melatonin Attenuates Contrast-Induced Nephropathy in Diabetic Rats: The Role of Interleukin-33 and Oxidative Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Didem Onk ◽  
Oruc Alper Onk ◽  
Kultigin Turkmen ◽  
Huseyin Serkan Erol ◽  
Tulin Akarsu Ayazoglu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Potential ◽  
Kidney Tissue ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Contrast Induced Nephropathy ◽  
Interleukin 33 ◽  
Sprague Dawley Rats ◽  
And Oxidative Stress

Background.Inflammation and oxidative stress (OxS) contribute to the pathogenesis of diabetic kidney disease (DKD) and contrast-induced nephropathy (CIN). Patients with DKD were found to be more prone to CIN. Interleukin-33 (IL-33) is a proinflammatory cytokine, but its role in DKD and CIN is unknown.Methods.Thirty male Sprague-Dawley rats were enrolled. The first group was comprised of healthy rats (HRs), whereas the other four groups were made up of diabetic rats (DRs), diabetic rats with contrast-induced nephropathy (CIN + DRs), melatonin-treated diabetic rats (MTDRs), and melatonin-treated CIN + DRs (MTCIN + DRs). All groups except the HRs received 50 mg/kg/day streptozotocin (STZ). CIN + DRs were constituted by administrating 1.5 mg/kg of intravenous radiocontrast dye on the 35th day. MTDRs and MTCIN + DRs were given 20 mg/kg/day of intraperitoneal injection of melatonin (MT) from the 28th day for the constitutive seven days.Results.We observed increased IL-33 in the kidney tissue following induction of CIN in DRs. To determine whether MT is effective in preventing CIN, we administered MT in CIN + DRs and demonstrated that kidney tissue levels of OxS markers, inflammatory cytokines, and IL-33 were significantly diminished in MTCIN + DRs compared with other groups without MT treatment (p<0.05).Conclusion.Inhibition of IL-33 with MT provides therapeutic potential in DKD with CIN.

Insulin administration abrogates perturbation of methyl group and homocysteine metabolism in streptozotocin-treated type 1 diabetic rats

2011 ◽  
Vol 301 (3) ◽  
pp. E560-E565 ◽  
Author(s):  
Kristin M. Nieman ◽  
Kevin L. Schalinske
Keyword(s):  
Blood Glucose ◽  
Regulatory Protein ◽  
Diabetic Rats ◽  
Plasma Homocysteine ◽  
Future Research ◽  
Sprague Dawley ◽  
Methyl Group ◽  
Sprague Dawley Rats ◽  
Blood Glucose Concentrations

Modifications in methyl group and homocysteine metabolism are associated with a number of pathologies, including vascular disease, cancer, and neural tube defects. A diabetic state is known to alter both methyl group and homocysteine metabolism, and glycine N-methyltransferase (GNMT) is a major regulatory protein that controls the supply and utilization of methyl groups. We have shown previously that diabetes induces GNMT expression and reduces plasma homocysteine pools by stimulating both its catabolism and folate-independent remethylation. This study was conducted to determine whether insulin plays a role in the control of homocysteine concentrations and GNMT as well as other key regulatory proteins. Male Sprague-Dawley rats were randomly assigned to one of three groups: control, streptozotocin (STZ)-induced diabetic (60 mg/kg body wt), and insulin-treated diabetic (1.0 U bid). After 5 days, rats were anesthetized (ketamine-xylazine) for procurement of blood and tissues. A 1.5-fold elevation in hepatic GNMT activity and hypohomocysteinemia in diabetic rats was completely prevented by insulin treatment. Additionally, diabetes-mediated alterations in methionine synthase, phosphatidylethanolamine N-methyltransferase, and DNA methylation were also prevented by insulin. We hypothesize that the concentration of blood glucose may represent a regulatory signal to modify GNMT and homocysteine. In support of this, blood glucose concentrations were negatively correlated with total plasma homocysteine ( r = −0.75, P < 0.001) and positively correlated with GNMT activity ( r = 0.77, P < 0.001). Future research will focus on further elucidating the role of glucose or insulin as a signal for regulating homocysteine and methyl group metabolism.

scholarly journals Folic acid as preventive therapy for hearing loss: effect of ototoxic drug consumption

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Carmen Morais-Moreno ◽  
María del Pilar Garzón-Riveros ◽  
Silvia Murillo-Cuesta ◽  
Lourdes Rodríguez-de la Rosa ◽  
Ana Montero ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Folic Acid ◽  
Stria Vascularis ◽  
Auditory Brainstem ◽  
Auditory Brainstem Responses ◽  
Control Group ◽  
Spiral Ligament ◽  
Folate Supplementation ◽  
Age Related ◽  
Ototoxic Drugs

AbstractIntroductionAge-related hearing loss (ARHL) is a sensory impairment, with a dramatic increase in its incidence, which is caused by genetic and environmental factors such as noise and ototoxic drugs. Recent studies correlated ARHL to elevated plasma homocysteine (Hcy) by folate deficiency, suggesting that reduction of Hcy levels by folate supplementation could potentially ameliorate ARHL.Hyperhomocysteinemia (HHcy), a status that contributes to ARHL, may also arise from malfunction of Hcy remethylation by betaine homocysteine S-methyltransferases (BHMTs) and methionine synthase in the methionine cycle. The expression and/or activity of these enzymes may be altered by ototoxic drugs, including paracetamol (APAP).ObjectiveTo determine the effect of APAP in cochlear morphology and function of control and Bhmt-/- mice, and to analyze putative preventive effects of folic acid (FA) supplementation.Materials and MethodsTwo-month-old Bhmt-/- mice (n = 47), with greater dependence on folate metabolism for Hcy remethylation, and Bhmt + / + mice (n = 42) were fed control or FA supplemented diets for 30 days. The last day APAP (250 mg/kg) or placebo were injected intraperitoneally.Hearing was evaluated by recording auditory brainstem responses (ABR) at the beginning of the experiment and after treatments. Picrosirius red staining was used for evaluation of the cochlear lateral wall cytoarchitecture. Plasma and hepatic metabolite levels were determined by HPLC or on Spinlab 100® autoanalyzer.ResultsLoss of Bhmt expression induced HHcy, but an impact on hearing acuity was not observed. Acute APAP administration did not induce ABR threshold shifts. However, following ototoxic treatment, changes of 5–17% in the areas of the stria vascularis and spiral ligament were detected between Bhmt-/- mice under different dietary treatments; cochlear structures of Bhmt-/- mice receiving APAP plus FA supplementation resemble those of the control group. APAP increases susceptibility to ototoxic damage in the presence of HHcy.DiscussionBHMT plays a central role in cochlear methionine metabolism. FA supplementation modulates Hcy levels, contributing to a proper remethylation status that prevents ARHL.

Epigenetic changes and alteration of Fbn1 and Col3A1 gene expression under hyperglycaemic and hyperinsulinaemic conditions

2010 ◽  
Vol 432 (2) ◽  
pp. 333-341 ◽  
Author(s):  
Anil B. Gaikwad ◽  
Jeena Gupta ◽  
Kulbhushan Tikoo
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Histone H3 ◽  
Diabetic Rats ◽  
Epigenetic Changes ◽  
Sprague Dawley ◽  
Fbn1 Gene ◽  
Matrix Gene ◽  
Col3a1 Gene

Little is known regarding the role of hyperglycaemia on histone H3 modifications and, in turn, altering the expression of genes during the development of diabetes-associated complications. In the present study, we have investigated the hyperinsulinaemia/hyperglycaemia-induced epigenetic changes and alteration of Fbn1 (fibrillin 1) and Col3A1 (collagen type III α1) gene expression. Insulin resistance and Type 2 diabetes in male Sprague–Dawley rats was developed by feeding rats an HFD (high-fat diet) and administering a low dose of STZ (streptozotocin). Hyperglycaemia induced deacetylation and dephosphorylation of histone H3 in the heart and kidneys of diabetic rats. Furthermore, mRNA expression of Fbn1 and Col3A1 increased in the kidneys and decreased in the heart under hyperglycaemic/hyperinsulinaemic conditions. Similar to mRNA expression, chromatin immunoprecipitation also showed an increase in the level of histone H3 acetylation of the Fbn1 gene, but not of the Col3A1 gene. Our present findings suggests that the change in expression of the Fbn1 gene is epigenetically regulated, but the expression of the Col3A1 gene may either be independent of epigenetic regulation or may involve other histone modifications. We provide the first evidence regarding the role of hyperglycaemia/hyperinsulinaemia in altering histone H3 modifications, which may result in the alteration of extracellular matrix gene expression.

A novel mechanism for angiotensin II formation in streptozotocin-diabetic rat glomeruli

2005 ◽  
Vol 288 (6) ◽  
pp. F1183-F1190 ◽  
Author(s):  
Rekha Singh ◽  
Ashok K. Singh ◽  
David J. Leehey
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Ang Ii ◽  
Sprague Dawley ◽  
New Information ◽  
Sprague Dawley Rats ◽  
And Control

Recent evidence suggests that the intrarenal renin-angiotensin system (RAS) may play an important role in the development of glomerular changes associated with diabetic nephropathy. In this study, the glomerular RAS was examined in male Sprague-Dawley rats made diabetic with streptozotocin (STZ), and the findings compared with those obtained in control nondiabetic rats. In diabetic rat glomerular extracts, angiotensinogen and angiotensin II (ANG II) levels were increased significantly by 2.2- and 1.9-fold, respectively, compared with nondiabetic controls. No significant differences in ANG I and angiotensin-converting enzyme (ACE) levels were observed between these groups. The HPLC analysis of the glomerular extracts demonstrated that exogenous ANG I was converted into various ANG peptides including ANG II, ANG(1–9), and ANG(1–7). A significant increase in formation of ANG II from exogenous ANG I was observed in STZ rats compared with control rats. Preincubation of glomerular extracts with captopril resulted in a 20–30% decrease in ANG II conversion from exogenous ANG I in diabetic and control rats. The possible role of ANG(1–9) in formation of ANG II was examined by HPLC. Exogenous ANG(1–9) in glomerular extracts was converted into ANG II, this conversion being significantly higher in STZ rats than in control rats. These findings provide new information that ANG(1–9) is produced in rat glomerular extracts, can be converted to ANG II, and that this conversion is also stimulated in diabetic rat glomeruli. Thus this study demonstrates that in diabetic rats, glomerular ANG II levels are increased due to an increase in angiotensinogen and an increase in the formation of ANG II.

scholarly journals The Protective Effects of Enalapril Maleate and Folic Acid Tablets against Contrast-Induced Nephropathy in Diabetic Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jiantong Hou ◽  
Gaoliang Yan ◽  
Bo Liu ◽  
Boqian Zhu ◽  
Yong Qiao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Folic Acid ◽  
Endothelial Dysfunction ◽  
Diabetic Rats ◽  
Tunel Staining ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Contrast Induced Nephropathy ◽  
Enalapril Maleate ◽  
Renal Vasoconstriction

Background. Renal vasoconstriction, oxidative stress, endothelial dysfunction, and apoptosis are the major causes of contrast-induced nephropathy (CIN). The aim of this study was to evaluate the protective effects of enalapril maleate and folic acid tablets on CIN in diabetic rats.Methods. Thirty-two Sprague-Dawley rats were divided into four groups: CIN (C), CIN + enalapril maleate (CE), CIN + folic acid (CF), and CIN + enalapril maleate and folic acid tablets (CEF). CE, CF, and CEF rats were treated orally with enalapril maleate, folic acid, or enalapril maleate and folic acid tablets, respectively, for 5 days. CIN was induced in all groups followed by analyzed biochemical parameters, oxidative stress markers, endothelial dysfunction parameters, renal histopathology, and TUNEL staining.Results. Serum creatinine, blood urea nitrogen, and malondialdehyde levels were lower in the CEF group than in the C group. Homocysteine, superoxide dismutase, glutathione peroxidase, and nitric oxide levels were higher in the CEF group than in the C group. Histopathology scores and percentage of apoptotic kidney cells in the CEF group were significantly decreased compared with those in the C group.Conclusions. These results suggest that enalapril maleate and folic acid tablets have a protective effect against CIN in diabetic rats.

Abstract 11029: Netrin-1 Alleviates Post-Resuscitation Myocardial Dysfunction in a Rat Model of Cardiac Arrest

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Lu Yin ◽  
Shen Zhao ◽  
JoongBum Moon ◽  
Peng Sun ◽  
Jiangang Wang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Rat Model ◽  
Myocardial Dysfunction ◽  
Saline Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Group 2

Introduction: Post-resuscitation myocardial dysfunction has been recognized as one of the major causes of fatal outcomes after initial successful cardiopulmonary resuscitation (CPR). Previous research demonstrated that Netrin-1 improved post ischemic injury cardiac function via preservation of mitochondrial integrity. In the present study, we investigated the role of netrin-1 after cardiac arrest. Hypothesis: We hypothesized that the netrin-1 alleviated post-resuscitation myocardial dysfunction in a rat model of cardiac arrest. Methods: A total of sixteen male Sprague-Dawley rats (450-550 g) were randomized to two groups as follows: (1) Control group (C group); (2) Netrin-1 group (N group). Ventricular fibrillation was induced and untreated for 8 mins followed by 8 mins of CPR. Netrin-1 or saline were given at the onset of precordial compression. Ejection fraction (EF) was measured by echocardiography at baseline, 1,2,3 and 4 hours after ROSC. Results: Eight rats were resuscitated in the netrin-1 group and 7 rats were resuscitated in the saline group. In both groups, EF decreased after resuscitation when compared to the baseline (#p < 0.05). In the netrin-1 group, EF decreased from ( 68.1±3.4)% at baseline to (51.1±5.0)% at 1 hour post-resuscitation. In the saline group, EF decreased from (67.7±2.1)% at baseline to (44.5±5.3)% at 1 hr post-resuscitation. EF was better in the netrin-1 group than in the saline group at 2, 3 and 4 hours post-resuscitation (*p < 0.05) ( Figure 1). Conclusion: Netrin-1 alleviates post-resuscitation myocardial dysfunction in a rat model of cardiac arrest.

scholarly journals Role of autonomic nervous system in chronic CNS-mediated antidiabetic action of leptin

2017 ◽  
Vol 312 (5) ◽  
pp. E420-E428 ◽  
Author(s):  
Alexandre A. da Silva ◽  
John E. Hall ◽  
Sydney P. Moak ◽  
Jackson Browning ◽  
Haley J. Houghton ◽  
...  
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Blood Glucose ◽  
Cardiovascular Effects ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Ganglionic Blockade ◽  
Autonomic Nervous ◽  
Sprague Dawley Rats

This study tested whether ganglionic blockade or hepatic vagotomy attenuates the chronic central nervous system (CNS)-mediated antidiabetic and cardiovascular effects of leptin. Male Sprague-Dawley rats were instrumented with telemetry probes and arterial and venous catheters for determination of blood pressure (BP), heart rate (HR), blood sampling, and intravenous (iv) infusions. An intracerebroventricular (ICV) cannula was placed into the brain lateral ventricle for infusion of leptin or vehicle. After control measurements, streptozotocin (STZ) was injected iv (50 mg/kg) to induce diabetes, and 5 days later leptin ( n = 6) or saline vehicle ( n = 5) was infused ICV for 12 days via osmotic pumps. Beginning on day 6 of leptin treatment, the ganglionic blocker hexamethonium (15 mg·kg−1·day−1 iv) was infused, while leptin infusion was continued, to assess the role of the autonomic nervous system. Induction of diabetes was associated with increases in blood glucose (98 ± 7 to 350 ± 19 mg/dl), food intake (23 ± 3 to 43 ± 3 g/day), decreases in HR (−70 ± 11 beats/min), polyuria, and increased water consumption, which were all completely normalized by ICV leptin infusion. Although hexamethonium attenuated leptin’s effect on HR, it failed to impair leptin’s ability to restore euglycemia or to prevent the polyuria or increased water intake in STZ-diabetic rats. We also found that after pretreatment with hexamethonium ( n = 8), ICV leptin infusion, during continued ganglionic blockade, completely normalized blood glucose in diabetic rats. In addition, selective hepatic vagotomy did not attenuate leptin’s ability to restore euglycemia in diabetic rats. These results suggest that leptin’s powerful chronic CNS antidiabetic actions are mediated primarily via nonautonomic mechanisms.

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