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Hyperlipidemia and oxidative stress are indispensable features of chronic kidney disease (CKD) that favor the development of atherogenic plaques and cardiovascular disease (CVD). A number of vasoactive mediators including proprotein convertase subtilisin-kexin type 9 (PCSK9), endothelin-1, nitric oxide, and angiotensin II have fundamental roles in the pathophysiology of atherosclerotic events; moreover, their levels are affected by dyslipidemia and oxidative stress due to renal dysfunction. Therefore, therapeutic measures aimed at correcting dyslipidemia and alleviating oxidative stress could potentially protect against CVD in CKD patients. In this review, we discuss the relation between dyslipidemia, oxidative stress, and vasoactive mediators as well as the available treatment options against these disturbances in CKD patients.

Due to the association of oxidative stress and telomere shortening, it was aimed in the present study to investigate the possibility whether cyclosporine-A exerts its nephrotoxic side effects via induction of oxidative stress-induced renal telomere shortening and senescent phenotype in renal tissues of rats. Renal oxidative stress markers, 8-hydroxydeoxyguanosine, malondialdehyde, and protein carbonyl groups were measured by standard methods. Telomere length and telomerase activity were also evaluated in kidney tissue samples. Results showed that cyclosporine-A treatment significantly (P < 0.05) enhanced renal malondialdehyde, 8-hydroxydeoxyguanosine, and protein carbonyl groups levels, decreased renal telomere length, and deteriorated renal function compared with the controls. Renal telomerase activity was not affected by cyclosporine-A. Renal telomere length could be considered as an important parameter of both oxidative stress and kidney function. Telomere shortening and accelerated kidney aging may be caused by cyclosporine-induced oxidative stress, indicating the potential mechanism of cyclosporine-induced nephrotoxicity., (© 2018 Wiley Periodicals, Inc.)

Statins, inhibitors of hydroxy methyl glutaryl coenzyme-A (HMG-CoA) reductase, are the most widely used drugs for treating hypercholesterolemia. However, statins can cause disabling myopathy as their main adverse effect. Several molecular mechanisms underlie the statin-induced myopathy including the decrease in the levels of essential mevalonate and cholesterol derivatives. This review discusses a further mechanism involving the loss of other anti-oxidant defenses besides ubiquinone (Co-Q) in skeletal muscles which produce a significant amount of reactive oxygen species (ROS). Therefore, to maintain their function, skeletal muscles need a high level of anti-oxidants.

Introduction: Calcineurin inhibitor nephrotoxicity is major problem after organ transplantation. It is multifactorial, but oxidative stress may have an important role in this process. It has been shown that angiotensin II receptor blockers have renoprotective effects but their molecular mechanism is largely unknown. Antioxidative effect is an important role of the recently known anti-aging protein, klotho. This study aimed to evaluate effect of valsartan in alleviation of cyclosporine A nephrotoxicity via a probable increase in serum klotho levels or decreasing oxidative stress., Materials and Methods: Thirty-two Sprague-Dawley rats were divided into 4 groups to receive 1 mL/kg/d of olive oil as control; 30 mg/kg/d of cyclosporine; 30 mg/kg/d of cyclosporine and 50 mg/kg/d of valsartan; and 50 mg/kg/d of valsartan. After the 6 weeks of administration period, serum levels of klotho and 8-hydroxydeoxyguanosine were measured using an enzyme-linked immunosorbent assay. Serum malondialdehyde level was measured spectrophotometrically., Results: The mean serum level of klotho was significantly lower in the cyclosporine group compared with control and valsartan groups. Klotho level in the valsartan group was significantly higher than those in the other groups. The cyclosporine group was detected to have significantly higher serum 8-hydroxydeoxyguanosine and malondialdehyde levels compared with the other study groups. The levels of klotho were negatively correlated with 8-hydroxydeoxyguanosine and malondialdehyde levels., Conclusions: Administration of valsartan may lead to attenuation of the nephrotoxic side effect of cyclosporine via enhancing klotho and decreasing oxidative stress levels.

Considering the importance of toll-like receptor (TLR) 4 and oxidative stress in the pathogenesis of autoimmune disorders, present study was designed to assess serum TLR4, 8-hydroxy-2′-deoxyguanosine (8-OHdG) as a marker of oxidative DNA damage, and total antioxidant capacity (TAC) in rheumatoid arthritis (RA) patients and to study their relation with disease activity and their predictive potential. 44 RA patients and 44 matched controls were studied. Disease activity score (DAS-28) was assessed. Serum TLR4, 8-OHdG and TAC were measured. The mean age of patients was 44 ± 10.4 years, 33 females and 11 males with and disease duration 5.5 ± 3.8 months. The mean DAS-28 was 4.6 ± 0.6 (3.45–6.01). Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were both positive in 20 patients. Compared to control, the mean ± SD of serum TLR4 (2.41 ± 4.50 vs. 1.20 ± 1.67 ng/ml), and 8-OHdG (67.67 ± 20.57 vs. 45.34 ± 30.61 ng/ml) were significantly higher in patients (p < 0.001); whilst serum TAC (1.3 ± 0.5 vs. 2.01 ± 0.55 µmol/L) was significantly lower (p < 0.001). TLR4, 8-OHdG were significantly increased and TAC decreased in patients with positive RF/anti-CCP compared to negative (p < 0.001, p = 0.005 and p = 0.036 respectively). TLR4 was significantly higher in patients with higher DAS-28 (p = 0.003) and both significantly correlated (p < 0.001). Areas under the ROC curve of TLR4 (0.87; 95%CI: 0.78–0.96) and 8-OHdG (0.88; 95%CI: 0.79–0.97) were greater than that of TAC (0.19, 95%CI: 0.09–0.29) (p < 0.001). The TLR4, 8-OHdG and TAC showed high predictive value in RA disease. TLR4 can be remarked as a sensitive and specific marker for determining disease activity in RA. [ABSTRACT FROM AUTHOR]

Objective: Behcet's disease (BD) is a chronic inflammatory disorder characterized by recurrent oral and genital aphthous ulcers, uveitis and skin lesions. Oxidative stress and inflammation have important role in the pathogenesis of BD. The aim of this study was to assess the effect of Nigella sativa (NS) oil administration on malondialdehyde (MDA), total anti-oxidant capacity (TAC), tumor necrosis factor-α (TNF-α), IL-10 and high sensitivity C-reactive protein (hs- CRP) levels in patients with BD. Materials and Methods: In this randomized, double-blind and placebo-controlled clinical trial, 96 BD patients were randomly assigned to NS or placebo groups. Study groups received 1000 mg/day NS oil and placebo soft gels for 8 weeks. Serum levels of TNF-α, IL-10, hs-CRP, MDA and TAC were measured before and after treatment. Results: Eighty-nine individuals completed the study. Significant decreases in the serum levels of MDA and increases in the serum levels of TAC were found in the NS group. However, differences in the changes of MDA and TAC in the NS and placebo groups were not significant. Pre- and post-intervention changes of TNF-α, IL-10 and hs-CRP levels in the NS group were non-significant. Conclusion: NS 1000 mg per day is probably not effective in reducing the inflammatory and oxidative markers in BD. [ABSTRACT FROM AUTHOR]

Introduction: Nephrotoxicity as a side effect caused by the immunosuppressive drug, cyclosporine-A (CsA), can be a major problem in transplant medicine. Oxidative stress may play an important role in the CsA-induced nephrotoxicity. It has been shown that the antihypertensive drug, valsartan (Val), has also renoprotective effects but, its molecular mechanism is largely unknown. In the present study, it was aimed to evaluate the Val effect in the alleviation of CsA nephrotoxicity via probable renal glutathione peroxidase (GPx) upregulation and oxidative stress decrease. Methods: Thirty-two Sprague-Dawley rats were divided into four groups based on CsA and/or Val administration: group A (Control, 1 mL/kg/day of olive oil as vehicle), group B (CsA, 30 mg/kg/day), group C (CsA+Val, 30+30 mg/kg/day), and group D (Val, 30 mg/kg/day). After the administration period (six weeks), renal GPx expression was evaluated by real-time polymerase chain reaction (PCR). Plasma levels of GPx and 8-Hydroxydeoxyguanosine (8-OHdG) were measured by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA) and protein carbonyl groups (PCG) were measured by spectrophotometer. Plasma levels of urea and creatinine were measured by an autoanalyzer. Results: CsA treatment led to the decrease in renal expression and plasma levels of GPx in comparison to other study groups. Rats received CsA were detected to have significantly (p<0.05) higher plasma 8-OHdG, MDA, PCG, urea, and creatinine levels in comparison to other groups. Plasma urea and creatinine levels were negatively correlated with renal GPx expression and positively correlated with the oxidative stress markers. Conclusion: Administration of Val may result in attenuating the nephrotoxic side effect of CsA via probable renal GPx upregulation, and subsequently oxidative stress decrease. [ABSTRACT FROM AUTHOR]

Background and Objectives: Oxidative stress has been implicated in various pathological consequences including such as cardiovascular disease , cancer, diabetes and aging. The present study investigated the effects of hydroalcoholic extract of Nasturtium Officinale on antioxidant status and DNA damage in arsenic -induced oxidative damage in liver and kidney tissue. Materials and Methods: In this experimental study ,48 male rats were selected and randomly divided into 6 groups: Group 1: normal healthy rat, group II was treated with sodium arsenite (SA) {i.p. injection at dose of 5.5 mg/kg body weight }, group III and group IV was treated with hydroalcoholic extract of N.Officinale (via gavage) at a dose of 200 and 500 mg/kg body weight respectively , group V and group VI was treated with hydroalcoholic extract of N.Officinale (via gavage) at a dose of 200 and 500 mg/kg body weight respectively + SA. Blood samples were collected and then examined antioxidant enzymes: Catalase (CAT), Superoxiddismutase (SOD) and Glutathion Peroxidase (GPx) activities, MDA (Malondialdehyde) content, 8OHdG concentration in liver and kidney. Results: Results of current study indicates that N.Officinale consumption significantly increased the activities of antioxidant enzymes and decreased MDA content, 8-OHdG(8-hydroxydeoxyguanosine) Concentration in liver. The consumption of plant extract significantly increased the activity of GPx in kidney. Conclusions: N.Officinale (Watercress) reduces the arsenic-induced oxidative damage in liver and it has the little protective effect in kidney. [ABSTRACT FROM AUTHOR]

Chemotherapeutic agents used in patients with cancer cause to generate the enormous amounts of free radicals associated with cell injury. In this study we assess the effects of chemotherapy regimen on oxidant/antioxidant status in patients with acute myeloid leukemia (AML). 38 newly diagnosed patients with acute myeloid leukemia were recruited in this study. All patients received cytarabine and daunorubicin as chemotherapy regimen. Plasma levels of malondialdehyde (MDA), total antioxidant status (TAS), and the levels of erythrocyte activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were determined before chemotherapy and 14 days after chemotherapy with cytarabine and daunorubicin. Plasma MDA concentrations increased significantly (from 2.68 ±0.89 nmol/L to 3.14 ±1.29 nmol/L) during the 14days post-chemotherapy period (P=0.04). Plasma TAS concentrations changed with chemotherapy from 1.09 ±0.15 mmol/L to 1.02 ±0.14 mmol/L with P=0.005. Erythrocyte SOD and GPX activity decreased overtime from 1157.24 ±543.61 U/g Hb to 984.01 ±419.09 U/g Hb (P=0.04) and 46.96 ±13.70 U/g Hb to 41.40 ±6.44 U/g Hb (P=0.02) respectively. We report here that there is an increase in malondialdehyde levels and a decrease in the levels of antioxidant enzymes and total antioxidant status. This suggests that chemotherapy causes these changes as a result of enormous production of reactive oxygen species in the patients with AML. Antioxidant supplementation must be approached with caution because of the probability of reduction the therapeutic efficacy of these cytotoxic drugs. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Tuberculosis remains one of the most common infectious diseases and a leading cause of mortality world wide. There is some evidence for the possible involvement of Mycobacterium tuberculosis in atherosclerosis. We aim to investigate total antioxidant capacity (TAC), red blood cell superoxide dismutase (SOD) activity, whole blood glutathione peroxidase (GPX) activity, low-density lipoprotein (LDL) susceptibility to oxidation, and malondialdehyde (MDA) levels in patients with pulmonary tuberculosis (PTB). Methods: Forty-five males with active PTB (case group) and 45 healthy age-matched males (control group) were enrolled in the study. TAC, SOD and GPX activities were determined by commercial ELISA kits. MDA levels were measured using the thiobarbituric acid method. LDL susceptibility to oxidation was assessed by measuring lag phase duration. Results: TAC, SOD and GPX activities, and lag phase duration in the case group were significantly lower than the control group (p =.002, p =.004, p =.008, and p =.004, respectively; independent), while the MDA levels was higher in case group (p =.024). Conclusions: Our findings suggest a higher susceptibility of LDL to oxidation and higher levels of lipid peroxidation, and therefore, a possible higher risk of atherosclerosis in patients with PTB. [Copyright &y& Elsevier]

Background: Many chemotherapeutic regimens used in the treatment of cancer generate free radicals that may be a part of their beneficial effects. The aim of this study was to assess the oxidative status in patients undergoing chemotherapy for acute myeloid leukemia (AML). Methods: Thirty-eight patients with AML (17 female and 21 male patients) with a mean age 34.05±12.49 years were included in the study. All the patients received cytarabine and daunorubicin as their standard induction therapy. Serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and also the erythrocyte superoxide dismutase and glutathione peroxidase activities were measured before and 14 days after chemotherapy. Results: Plasma malondialdehyde concentrations increased significantly (from a former 2.68±0.89 nmol/ml to 3.14±1.29 nmol/ml) 14 days post chemotherapy (p=0.04). Moreover, the total plasma antioxidant capacity changed from 1.09±0.15 mmol/L to 1.02±0.14 mmol/L (p=0.005). Erythrocyte superoxide dismutase and glutathione peroxidase activity decreased over time from 1157.24±543.61 U/gHb to 984.01±419.09 U/gHb (p=0.04) and 46.96±13.70 U/gHb to 41.40±6.44 U/gHb (p=0.02), respectively. Conclusion: In this study, an increase in malondialdehyde levels and a decrease in the levels of antioxidant enzymes and total antioxidant capacity were observed. It seems that chemotherapy by cytarabine and daunorubicin generates enormous amounts of free radicals in patients undergoing the treatment for AML. Use of antioxidant supplementation during chemotherapy i is discouraged as it may interfere with the generation of free radicals that may be a part of the therapeutic efficacy of these drugs. [ABSTRACT FROM AUTHOR]

One of the important factors in the occurrence of acute kidney injury (AKI) among renal transplant patients (RTPs) is ischemia reperfusion injury (IRI). The current study aimed at determining the anti-inflammatory and anti-oxidative effects of melatonin on the complications of IRI and the level of Klotho expression in these patients. A total of 40 renal transplant candidates were randomly assigned into placebo or melatonin group receiving the same dose of 3 mg/day. In order to measure serum melatonin levels, inflammatory and oxidative stress factors, renal function biomarkers, and Klotho gene/protein expression, venous blood samples were taken from patients over two different time points, i e, 24 h before the transplantation and at discharge from hospital. Melatonin was associated with improvement in renal transplantation, since the serum level of neutrophil gelatinase-associated lipocalin, as a renal functional marker, significantly decreased (P <.001). The effect of melatonin as a suppressor of inflammation and oxidative stress was also evident in the melatonin group due to a significant reduction in the serum levels of MDA, CP, 8-OHdG, and TNF-α markers (P <.001). Reduction in serum levels of renal function and oxidative stress/inflammatory markers in the melatonin group indicates that melatonin can inhibit IRI outcomes in RTPs through its anti-oxidant and anti-inflammatory properties. However, these properties do not appear as a result of influence on the level of Klotho gene/protein expression. • Ischemia/reperfusion injury following renal transplantation is one of the most important factors in the incidence and development of AKI. • Ischemia/reperfusion injury via high production of oxidative stress and inflammatory markers can induce AKI. • Administrated melatonin leads to improvement of kidney functional biomarkers and amelioration of oxidative stress and inflammatory markers. [ABSTRACT FROM AUTHOR]

Background and Objectives: Exudative Age Related Macular degeneration (E-ARMD) is a multifactorial disease. The aim of the present study was to investigate the plasma levels of asymmetric dimethylarginine (ADMA) as a factor involved in oxidative stress in patients with E-ARMD. Materials and Methods: In a case-control study, 45 patients with E-ARMD were compared with 45 sex- and age- matched healthy controls. The plasma levels of ADMA were measured by Enzyme-Linked ImmunoSorbant Assay (ELISA) method in both groups. Results: The levels of ADMA were higher in patients with E-ARMD (0.84±0.23 μM) than normal controls (0.71±0.25 μM) and the difference was statistically significant (p=0.012). Conclusion: High levels of ADMA as an endogenous nitric oxide synthase inhibitors may have a role in oxidative stress in E-ARMD patients. [ABSTRACT FROM AUTHOR]

Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress induction that leads to the formation of atherosclerotic plaque. Oxidized low-density lipoprotein particles (Ox-LDL) have a key role in the pathogenesis of atherosclerosis. The lipid-lowering properties and antioxidants of the grape seed can be beneficial in atherosclerosis prevention. We conducted a randomized double-blind placebo-controlled crossover clinical trial. Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape seed extract (RGSE) or placebo for 8 weeks. After an 8-week washout period, the groups were crossed over for another 8 weeks. Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase. RGSE consumption reduced total cholesterol (−10.68±26.76 mg/dL, P=.015), LDL cholesterol (−9.66±23.92 mg/dL, P=.014), and Ox-LDL (−5.47±12.12 mg/dL, P=.008). While triglyceride and very low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased by RGSE, the changes were not statistically significant. RGSE consumption decreases Ox-LDL and has beneficial effects on lipid profile-consequently decreasing the risk of atherosclerosis and cardiovascular disorders-in mild hyperlipidemic individuals. [ABSTRACT FROM AUTHOR]