scholarly journals Association of Genetic Polymorphisms in Oxidative Stress and Inflammation Pathways with Glaucoma Risk and Phenotype

2021 ◽  
Vol 10 (5) ◽  
pp. 1148
Author(s):  
Makedonka Atanasovska Velkovska ◽  
Katja Goričar ◽  
Tanja Blagus ◽  
Vita Dolžan ◽  
Barbara Cvenkel

Oxidative stress and neuroinflammation are involved in the pathogenesis and progression of glaucoma. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in inflammation and oxidative stress genes on the risk of glaucoma, the patients’ clinical characteristics and the glaucoma phenotype. In total, 307 patients with primary open-angle glaucoma or ocular hypertension were enrolled. The control group included 339 healthy Slovenian blood donors. DNA was isolated from peripheral blood. Genotyping was performed for SOD2 rs4880, CAT rs1001179, GPX1 rs1050450, GSTP1 rs1695, GSTM1 gene deletion, GSTT1 gene deletion, IL1B rs1143623, IL1B rs16944, IL6 rs1800795 and TNF rs1800629. We found a nominally significant association of GSTM1 gene deletion with decreased risk of ocular hypertension and a protective role of IL1B rs16944 and IL6 rs1800629 in the risk of glaucoma. The CT and TT genotypes of GPX1 rs1050450 were significantly associated with advanced disease, lower intraocular pressure and a larger vertical cup–disc ratio. In conclusion, genetic variability in IL1B and IL6 may be associated with glaucoma risk, while GPX and TNF may be associated with the glaucoma phenotype. In the future, improved knowledge of these pathways has the potential for new strategies and personalised treatment of glaucoma.

2019 ◽  
Vol 244 (18) ◽  
pp. 1688-1694 ◽  
Author(s):  
Amos O Abolaji ◽  
Victor O Ajala ◽  
Janet O Adigun ◽  
Isaac A Adedara ◽  
Hellen W Kinyi ◽  
...  

Sodium fluoride (NaF) is used in water fluoridation and dental products such as mouth rinses and toothpastes. Resveratrol is a natural polyphenol with antioxidant and anti-inflammatory properties. The present study was carried out to evaluate the toxicity of NaF and the protective role of resveratrol in Drosophila melanogaster. For longevity assay, Harwich strain of D. melanogaster was treated with NaF (0, 10, 30, 50, 70 and 90 mg/kg diet) throughout the lifespan and daily mortality recorded. Then, flies were again treated with similar doses of NaF for seven days to evaluate survival rate and oxidative stress markers. Thereafter, 60 mg resveratrol/kg diet was selected to determine its ameliorative role in NaF (70 mg/kg)-induced toxicity in flies: Group A (control), Group B (60 mg resveratrol/kg diet), Group C (70 mg NaF/kg diet), and Group D (resveratrol, 60 mg/kg diet) + NaF, 70 mg/kg diet). Thereafter, Glutathione-S-transferase (GST), catalase and acetylcholinesterase (AchE) activities, as well as total thiol (T-SH), nitrites/nitrates and hydrogen peroxide (H2O2) levels were determined. The results showed that resveratrol prevented NaF-induced elevation of H2O2 and nitrites/nitrates levels, as well as catalase activity. In addition, resveratrol restored NaF-induced inhibition of GST and AChE activities and depletion of T-SH content ( P < 0.05). Conclusively, resveratrol offered protective benefit against NaF-mediated toxicity in flies due to its antioxidant and anti-inflammatory properties. Impact statement D. melanogaster was used to understand the impact of NaF on lifespan and emergence rate as well as the rescue role of resveratrol. These parameters are difficult to carry out in previously used models such as rodents. This further enforces in part, the suitability of D. melanogaster in studying NaF-induced toxicity and the therapeutic effects of drugs. Additionally, we found that resveratrol rescued D. melanogaster from oxidative stress-induced by sodium fluoride (NaF) administration. This study is of public health significance as it indicated that the consumption of fruits rich in resveratrol such as grapes may offer protective role against inadvertent exposure to NaF and related chemicals.


2020 ◽  
Vol 10 (5) ◽  
pp. 578-586
Author(s):  
Areeg M. Abdelrazek ◽  
Shimaa A. Haredy

Background: Busulfan (Bu) is an anticancer drug with a variety of adverse effects for cancer patients. Oxidative stress has been considered as a common pathological mechanism and it has a key role in the initiation and progression of liver injury by Bu. Aim: The study aimed to evaluate the antioxidant impact of L-Carnitine and Coenzyme Q10 and their protective role against oxidative stress damage in liver tissues. Methods and Material: Thirty-six albino rats were divided equally into six groups. G1 (con), received I.P. injection of DMSO plus 1 ml of distilled water daily by oral gavages; G2 (Bu), received I.P. injection of Bu plus 1 ml of the distilled water daily; G3 (L-Car), received 1 ml of L-Car orally; G4 (Bu + L-Car) received I.P. injection of Bu plus 1 ml of L-Car, G5 (CoQ10) 1 ml of CoQ10 daily; and G6 (Bu + CoQ10) received I.P. injection of Bu plus 1 ml of CoQ10 daily. Results: The recent data showed that Bu induced significant (P<0.05) elevation in serum ALT, AST, liver GSSG, NO, MDA and 8-OHDG, while showing significant (P<0.05) decrease in liver GSH and ATP. On the other hand, L-Carnitine and Coenzyme Q10 ameliorated the negative effects prompted by Bu. Immunohistochemical expression of caspase-3 in liver tissues reported pathological alterations in Bu group while also showed significant recovery in L-Car more than CoQ10. Conclusion: L-Car, as well as CoQ10, can enhance the hepatotoxic effects of Bu by promoting energy production in oxidative phosphorylation process and by scavenging the free radicals.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3167
Author(s):  
Flavia Buonaurio ◽  
Maria Luisa Astolfi ◽  
Daniela Pigini ◽  
Giovanna Tranfo ◽  
Silvia Canepari ◽  
...  

Urinary concentrations of 16 different exposure biomarkers to metals were determined at the beginning and at the end of a working shift on a group of workers in the metal carpentry industry. Five different oxidative stress biomarkers were also measured, such as the oxidation products of RNA and DNA metabolized and excreted in the urine. The results of workers exposed to metals were compared to those of a control group. The metal concentrations found in these workers were well below the occupational exposure limit values and exceeded the mean concentrations of the same metals in the urine of the control group by a factor of four at maximum. Barium (Ba), mercury (Hg), lead (Pb) and strontium (Sr) were correlated with the RNA oxidative stress biomarker, 8-oxo-7, 8-dihydroguanosine (8-oxoGuo), which was found able to discriminate exposed workers from controls with a high level of specificity and sensitivity. The power of this early diagnostic technique was assessed by means of the ROC curve. Ba, rubidium (Rb), Sr, tellurium (Te), and vanadium (V) were correlated with the level of the protein oxidation biomarker 3-Nitrotyrosine (3-NO2Tyr), and Ba, beryllium (Be), copper (Cu), and Rb with 5-methylcytidine (5-MeCyt), an epigenetic marker of RNA damage. These effect biomarkers can help in identifying those workers that can be defined as “occupationally exposed” even at low exposure levels, and they can provide information about the impact that such doses have on their health.


Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1332
Author(s):  
Gilda M. Iova ◽  
Horia Calniceanu ◽  
Adelina Popa ◽  
Camelia A. Szuhanek ◽  
Olivia Marcu ◽  
...  

Background: There is a growing interest in the correlation between antioxidants and periodontal disease. In this study, we aimed to investigate the effect of oxidative stress and the impact of two antioxidants, curcumin and rutin, respectively, in the etiopathology of experimentally induced periodontitis in diabetic rats. Methods: Fifty Wistar albino rats were randomly divided into five groups and were induced with diabetes mellitus and periodontitis: (1) (CONTROL)—control group, (2) (DPP)—experimentally induced diabetes mellitus and periodontitis, (3) (DPC)—experimentally induced diabetes mellitus and periodontitis treated with curcumin (C), (4) (DPR)—experimentally induced diabetes mellitus and periodontitis treated with rutin (R) and (5) (DPCR)—experimentally induced diabetes mellitus and periodontitis treated with C and R. We evaluated malondialdehyde (MDA) as a biomarker of oxidative stress and reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG and catalase (CAT) as biomarkers of the antioxidant capacity in blood harvested from the animals we tested. The MDA levels and CAT activities were also evaluated in the gingival tissue. Results: The control group effect was statistically significantly different from any other groups, regardless of whether or not the treatment was applied. There was also a significant difference between the untreated group and the three treatment groups for variables MDA, GSH, GSSG, GSH/GSSG and CAT. There was no significant difference in the mean effect for the MDA, GSH, GSSG, GSH/GSSG and CAT variables in the treated groups of rats with curcumin, rutin and the combination of curcumin and rutin. Conclusions: The oral administration of curcumin and rutin, single or combined, could reduce the oxidative stress and enhance the antioxidant status in hyperglycemic periodontitis rats.


Author(s):  
D. Kiessling ◽  
C. Rennings ◽  
M. Hild ◽  
A. Lappas ◽  
T. S. Dietlein ◽  
...  

Abstract Purpose To determine the impact of failed ab-interno trabeculectomy on the postoperative outcome of subsequent XEN45 gel stent (Allergan, CA, USA) implantation in pseudophakic eyes. Methods In this retrospective single-center study, we included 60 pseudophakic eyes from 60 participants who underwent XEN45 gel stent implantation. Thirty eyes each underwent primary stent implantation (control group) or had previously undergone a failed ab-interno trabeculectomy (trabectome group). The groups were matched at a 1:1 ratio based on the following criteria: preoperative and maximum Intraocular pressure (IOP), preoperative medication score, cup/disk-ratio, follow-up time, best-corrected visual acuity at baseline, age, and the proportion of patients classified as primary open angle glaucoma or exfoliation glaucoma. We defined a successful surgery by the following three scores: an IOP reduction > 20% and IOP at the longest follow-up < 21 mmHg (Score A) or < 18 mmHg (Score B) or IOP ≤ 15 mmHg and an IOP reduction ≥ 40% (Score C). One open conjunctival revision was allowed in all scores, and a repeat surgery was considered a failure. Results Following an average follow-up period of 22 ± 12 months, we observed a mean IOP reduction of 38%, from 23.5 ± 5.2–14.5 ± 5.0 mmHg. Comparative analyses between the groups did not reveal a significant difference in the postoperative IOP, postoperative medication score, side effects, revision rate, repeat surgery rate, or success rate. Conclusions Trabectome is a viable first-line procedure for medically uncontrolled glaucoma before filtering ab-interno microstent surgery is considered.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Lukasz Markiewicz ◽  
Dariusz Pytel ◽  
Bartosz Mucha ◽  
Katarzyna Szymanek ◽  
Jerzy Szaflik ◽  
...  

The aim of presented work was to analyze the impact of particular polymorphic changes in the promoter regions of the -1607 1G/2GMMP1, -1562 C/TMMP9, -82 A/GMMP12, -511 C/TIL-1β, and 372 T/CTIMP1genes on their expression level in POAG patients. Blood and aqueous humor samples acquired from 50 patients with POAG and 50 control subjects were used for QPCR and protein levels analysis by ELISA.In vivopromoter activity assays were carried on HTM cells using dual luciferase assay. All studied subjects underwent ophthalmic examination, including BCVA, intraocular pressure, slit-lamp examination, gonioscopy, HRT, and OCT scans. Patients with POAG are characterized by an increased mRNA expression ofMMP1,MMP9,MMP12, andIL-1βgenes as compared to the control group (P<0.001). Aqueous humor acquired from patients with POAG displayed increased protein expression of MMP1, MMP9, MMP12, and IL-1βcompared to the control group (P<0.001). Allele -1607 1G ofMMP1gene possesses only 42,91% of the -1607 2G allele transcriptional activity and allele -1562 C ofMMP9gene possesses only 21,86% of the -1562 T allele. Increased expression levels of metalloproteinases can be considered as a risk factor for the development of POAG.


2017 ◽  
Vol 11 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Irini P. Chatziralli ◽  
George Theodossiadis ◽  
Prodromos Dimitriadis ◽  
Michail Charalambidis ◽  
Antonios Agorastos ◽  
...  

Background:Several studies have focused on oxidative stress on diabetes mellitus (DM). Our purpose was to investigate the impact of oxidative stress on progression of diabetic retinopathy (DR) in insulin-dependenttype 2DM patients, measuring serum malondialdehyde (MDA), as well as to examine the effect of vitamin E on DR progression in the above-mentioned patients.Methods:Participants in the study were 282 insulin-dependenttype 2DM patients with DR. All participants underwent a thorough ophthalmological examination, so as to grade DR, along with serum MDA measurement. All participants received 300mg vitamin E daily for 3 months and were examined again. Serum MDA pre- and post-intake of Vitamin E was the main outcome.Results:Serum MDA was positively associated with DR stage, while there was a statistically significant difference pre- and post-intake of vitamin E in all DR stages. In a subgroup analysis of patients with proliferative DR, there was a significant difference at baseline between patients who have received prior laser photocoagulation and the treatment naïve patients, while after intake of vitamin E, no statistically significant difference was noticed.Conclusion:Oxidative stress has been found to play significant role in the pathogenesis and progression of DR, while vitamin E seems to reduce MDA levels and subsequent oxidative stress, suggesting that it might have protective role in DR progression.


2011 ◽  
Vol 31 (6) ◽  
pp. 565-573 ◽  
Author(s):  
M Tutanc ◽  
V Arica ◽  
N Yılmaz ◽  
A Nacar ◽  
I Zararsiz ◽  
...  

Aim: In cyclosporin-A (CsA)-induced toxicity, oxidative stress has been implicated as a potential responsible mechanism. Therefore, we aimed to investigate the protective role of erdosteine against CsA-induced nephrotoxicity in terms of tissue oxidant/antioxidant parameters and light microscopy in rats. Materials and methods: Wistar albino rats were randomly separated into four groups. Group 1 rats treated with sodium chloride served as the control, group 2 rats were treated with CsA, group 3 with CsA plus erdosteine, and group 4 with erdosteine alone. Animals were killed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (Cr), uric acid (UA), total protein (TP), and albumin (ALB) levels. Kidney sections were analyzed for malondialdehyde (MDA) and nitric oxide (NO) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as for histopathological changes. Results: In the CsA group, MDA, GSH-Px, BUN, and Cr levels were increased. The TP and ALB levels were decreased. These changes had been improved by erdosteine administration. Other biochemical parameters did not show any significant change. Conclusion: These results indicate that erdosteine produces a protective mechanism against CsA-induced nephrotoxicity and suggest a role of oxidative stress in pathogenesis.


Biomedicine ◽  
2020 ◽  
Vol 39 (2) ◽  
pp. 333-338
Author(s):  
Kalaivani Manokaran ◽  
Vasanthalaxmi Krishnananda Rao ◽  
Nilima . ◽  
Manjula Shimoga Durgoji Rao ◽  
Sucheta Prasanna Kumar

Introduction and Aim: Oxidative stress plays a very important role in endosulfan-induced toxic effects on reproductive organs. Vitamin C is a potent antioxidant which plays an important role in decreasing oxidative stress. The present study was aimed to investigate the protective role of vitamin C against endosulfan-induced testicular toxicity in Wistar rats. To investigate a protective effect of vitamin C against endosulfan induced toxicity on biochemical changes. Materials and Methods: Seventy male neonatal Wistar rats were divided into  seven groups. The group  I was taken as the control group, the endosulfan-treated were grouped into II (3 mg/kg body weight (BW) and group III (6 mg/kg BW), Group IV (9 mg/kg BW) and Group V (12 mg/kg BW). Group VI (9 mg/kg BW) and group VII (12 mg/kg BW) were pretreated with vitamin C (20 mg/kg BW) for 60 days. After  the experimental procedures, the testicular weight, lactate dehydrogenase (LDH) enzyme and testosterone in plasma, LDH, steroidogenic enzymes 3?-HSD and 17?-HSD in testis were evaluated. One-way ANOVA was used to determine the statistical significance. Results: Significant improvement in the testicular weight (P<0.05) , LDH (P<0.05) levels both in plasma and testis, increase in testosterone(P<0.001) and steroidogenic enzyme levels(P<0.001) was observed in the group pretreated with vitamin C treated group when compared to the endosulfan treated group. Conclusion: Vitamin C decreases the toxic effect of endosulfan on testis. The present action might be  due to its antioxidative properties.


2020 ◽  
Author(s):  
Ran Xia ◽  
Na Shu ◽  
Huixian Cui ◽  
JORGE AGUSTÍN TRUJILLO PERDOMO ◽  
Hong Zhang ◽  
...  

Abstract AIMThe aim of the present study was to characterize the rhythm of 24-h intraocular pressure (IOP) and ocular perfusion pressure (OPP) in patients with ocular hypertension (OHTN), in order to provide a reference for the clinical diagnosis and treatment of OHTN. METHODSAccording to the diagnostic criteria, 107 patients with OHTN were included, and an age- and sex-matched healthy control group (71 patients) was selected. The IOP and blood pressure (BP) of the OHTN and the healthy control groups were recorded every 2 h over a 24-h period. BP was measured using a digital automatic BP monitor, and IOP was measured using a non-contact tonometer. RESULTSThe maximum, minimum and mean IOP were significantly higher in subjects with OHTN than in the healthy control group (P<0.05), and the maximum, minimum and mean MOPP were significantly lower in the OHTN group than in the healthy control group (P<0.05). The minimum and mean SOPP and DOPP values of the OHTN group were lower than those of the healthy control group (P<0.05), and the IOP, MOPP, SOPP and DOPP diurnal and nocturnal fluctuation values were significantly greater in the OHTN group than in the healthy control group (P<0.05). The peak and trough IOP times of the two groups coincided, which tended to be low during the day and higher at night. The peak and trough MOPP and SOPP times of the two groups also coincided, and were primarily higher during the day and lower at night. The 24-h DOPP in the healthy control group was generally higher during the daytime and lower at night, with peak values between 19:00-23:00 h, and trough values between 3:00-7:00 h. No obvious day-to-night fluctuations were observed in the OHTN group. CONCLUSIONThe OPP of patients with OHTN is lower, and the 24-h OPP fluctuates more than that of healthy control subjects. This may be an important blood flow factor for the progression to primary open angle glaucoma in patients with OHTN.


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