Is the Clinical Course of Non-Arteritic Ischemic Optic Neuropathy Associated with Oxidative Damage and the Dynamics of the Antioxidant Response?

Purpose: Oxidative stress is known to be a decisive factor in the wide etiopathogenesis of optic neuropathy. This study aimed to comprehensively evaluate the interaction of optic neuropathy’s clinical course with systemic oxidative damage and antioxidant response dynamics in a large series.Methods: This case-controlled clinical study included 33 non-arteritic anterior ischemic optic neuropathy patients and 32 healthy individuals. Extensive systemic oxidation profiles were statistically compared between the two groups, and correlations between the clinical and biochemical data in the patient group were analyzed.Results: Vitamin E and MDA levels were significantly higher in the patient group. Significant correlations were observed in the analyses between clinical findings and oxidative stress parameters. Correlations between vitamin E and intraocular pressure, between B12 and cup-to-disc ratio, between antioxidant glutathione and SOD enzyme systems, and between uric acid and age were found to be very significant. As significant correlations were found in either clinical and biochemical data or in oxidative stress parameters, correlations between vitamin E and cholesterol, MDA was found to be very significant. Conclusions: This study not only supplies significant information regarding oxidative damage and antioxidant response in NAION, but also points out the specific interactions of neuromodulators, like vitamin E, in intracellular signaling pathways and regulation mechanisms. A better reading of these connections may help improve diagnosis, follow-ups and treatment criteria and strategies.

Assessment of Glycemic Control, Renal Function, and Oxidative Stress Parameters in Type 2 Diabetes MellitusPatients

Diabetes mellitus (T2DM) is a multifactorial syndrome that israpidly rising in all the continents ofthe globe, causing elevated blood sugar levels in affected people. A sample of 81 Iraqi T2DM patients was investigated based on several parameters. Glycemic control parameters includedlevels of fasting blood glucose (FBG),glycated hemoglobin (HbA1C), and insulin, along with insulin resistance (IR) and insulin sensitivity (IS). Renal function tests includedmeasuring the blood levels of urea and creatinine. Oxidative stress parameters included total antioxidant capacity (TAC) and thelevel of reactive oxygen species (ROS). The results of the presentstudy showed a highly significant (P˂0.01) increase in FBG, HbA1c, insulin and IR levels in T2DM patients as compared to control.Insulin sensitivity showed a highly significant (p˂0.01) decrease in patients compared with control.Urea and creatinine levelsincreased in T2DM patients, but the differences were insignificant. TAC levelsignificantly (P<0.05) increased in patients compared with control. Also, the levels of ROSrevealed a highly significant (P<0.01) increasein T2DM patients compared with the control. Correlation analysis showedthat FBG has a highly significant (P<0.01) positive correlation with IR, urea, creatinine and ROS, as well as a significant (P<0.05) positive correlation with TAC. However, FBG shows a highlysignificant (P< 0.01) inverse correlation with IS. The levels of HbA1C show a significant (P<0.05) positive correlation with IR, creatinine, and TAC, whereas ithas a highly significant (P<0.01) positive relation with ROS. However, HbA1C level has a highly significant (P<0.01) inverse relation with IS. Insulin has highly significant (P<0.01) positive and negative associations with IR and IS, respectively.IR showshighlya significant (P<0.01) inverse correlation with IS, significant (P<0.05) positive correlation with creatinine, and highly significant (P<0.01) positive correlation with ROS. IS has a significant(P< 0.05) inverse correlation with urea. Urea shows a highly significant (P<0.01) positive correlation with creatinine. TAC has a significant (P<0.05) inverse correlation with ROS. Conclusion: diabetic patients revealed poor glycemic control. Fluctuating blood glucose concentrations may contribute significantly to oxidative stress, probablyeven more than chronic hyperglycemia. The observed significant positive correlation between FBG and the other tested parameters revealed that hyperglycemia is an obvious independent risk factor for T2DM progression.

The possible alleviating effect of garlic supplement on the neural retina in a rat model of hypercholesterolemia: a histological and immunohistochemical study

The purpose of this work was to prove that oxidative stress is the main mechanism responsible for retinal neurodegenerative changes, subsequent apoptosis, and inflammatory cytokine release in rats fed with a high cholesterol diet (HCD) and determine the role of garlic in alleviating these changes. Forty rats were equally divided into four groups: control, garlic-treated (positive control), HCD, and HCD + garlic-treated (HCD + G). By the end of the experiment (24 weeks) blood samples were collected for assessment of serum lipid profile, oxidative stress parameters, and plasma levels of IL-6 and TNF-α. Both eyes of the rats were enucleated; one was used for light microscopic examination and the other for electron microscopic examination. There was a significant increase in the levels of serum lipids, oxidative stress parameters, IL-6 and TNF-α, and area of expression of caspase-3 in the HCD group compared to both the control and HCD + G groups. Histological examination revealed degenerative changes in all layers of the neural retina in the HCD group. Garlic administration resulted in a significant improvement in the biochemical, immunohistochemical, and histological characteristics of hypercholesterolemic rats. These findings support the hypotheses that garlic has strong antioxidant, anti-apoptotic, and anti-inflammatory properties. Garlic ameliorates the neurodegenerative changes in the neural retina of hypercholesteremic rats.

Regulation of free radical processes in healthy volunteers during experimental hyperthermia and in patients with coronary artery disease during summer heat waves

Background. In view of the worsening forecast for global temperature rise worldwide, it seems relevant to study the effects of abnormal heat waves on systemic regulatory processes in people with chronic diseases, in particular coronary artery disease (CAD).Aims. This study aimed to investigate the effect of hyperthermia on oxidative stress parameters in patients with various severity of CAD and in healthy subjects.Materials and methods. We studied the level of malonic dialdehyde (MDA) and the activity of Cu,Zn-containing superoxide dismutase (Cu,Zn-SOD) in healthy subjects under conditions of 30-day long simulated hyperthermia and in patients with different severity of CAD after the summer heat wavesResults. We revealed signs of oxidative stress in healthy volunteers during model hyperthermia that manifested as an increase in content of MDA in blood plasma. At the same time we observed increasing activity of Cu,Zn-SOD in erythrocytes that utilizes reactive oxygen species. The increase of Cu,Zn-SOD activity started with a certain latency what also can be explained by de novo enzyme biosynthesis induction. We also studied oxidative stress parameters in patients at high and moderate cardiovascular risk according to the SCORE risk chart with uncomplicated CAD course and in patients with complicated CAD with severe coronary damage according to angiography during the summer heat waves. We observed accumulation of MDA in blood plasma and increasing activity of erythrocyte Cu,Zn-SOD in patients with uncomplicated CAD. At the same time we noted that accumulation of MDA in blood plasma was not followed by any increase in activity of red blood cell Cu,Zn-SOD in patients with severe complicated CAD. This fact indicates dysregulation of free radical processes in patients with severe course of CAD during the heat waves.Conclusions. The dysregulation of free-radical processes in patients with a severe clinical course of CAD has been revealed.

Protective and Therapeutic Effects of Orlistat on Metabolic Syndrome and Oxidative Stress in High-Fat Diet-Induced Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in Rats: Role on Nrf2 Activation

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an excessive buildup of liver lipids closely associated with various kinds of undesirable metabolic effects and oxidative stress. We aimed to investigate the protective and therapeutic effects of orlistat on metabolic syndrome and oxidative stress parameters in high-fat diet (HFD) induced-MAFLD rats. Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6/group), i.e., Normal control (N), HFD, HFD + orlistat (HFD + O) (10 mg/kg/day administered concomitantly for 12 weeks as a protective model), and obese+orlistat (OB + O) (10 mg/kg/day administered 6 weeks after induction of obesity as a therapeutic model) groups. After 12 weeks, the HFD group had significantly increased Lee obesity index, serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, triglyceride, low-density lipoprotein levels, liver total cholesterol and triglyceride levels, insulin resistance and non-alcoholic steatohepatitis (NASH) together with decreased serum high-density lipoprotein level. Additionally, the HFD group also showed increased Nrf2 translocation to the nucleus with high Keap1 expression and increased liver oxidative stress parameters. Orlistat significantly improved all these alterations in HFD rats. We demonstrated that orlistat might have protective and therapeutic effects against HFD-induced MAFLD rats by its activation on Nrf2 signaling pathway, which subsequently improved metabolic syndrome and oxidative stress parameters.

Ketogal Safety Profile in Human Primary Colonic Epithelial Cells and in Mice

In our previous studies, a ketorolac–galactose conjugate (ketogal) showed prolonged anti-inflammatory and analgesic activity, causing less gastric ulcerogenic effect and renal toxicity than its parent drug ketorolac. In order to demonstrate the safer profile of ketogal compared to ketorolac, histopathological changes in the small intestine and liver using three staining techniques before and after repeated oral administration in mice with ketorolac or an equimolecular dose of its galactosylated prodrug ketogal were assessed. Cytotoxicity and oxidative stress parameters were evaluated and compared in ketorolac- and ketogal-treated Human Primary Colonic Epithelial cells at different concentrations and incubation times. Evidence of mitochondrial oxidative stress was found after ketorolac treatment; this was attributable to altered mitochondrial membrane depolarization and oxidative stress parameters. No mitochondrial damage was observed after ketogal treatment. In ketorolac-treated mice, severe subepithelial vacuolation and erosion with inflammatory infiltrates and edematous area in the intestinal tissues were noted, as well as alterations in sinusoidal spaces and hepatocytes with foamy cytoplasm. In contrast, treatment with ketogal provided a significant improvement in the morphology of both organs. The prodrug clearly demonstrated a safer profile than its parent drug both in vitro and ex vivo, confirming that ketogal is a strategic alternative to ketorolac.