Endogenous Antioxidant Agent Research Articles

Vincristine attenuates isoprenaline-induced cardiac hypertrophy in male Wistar rats via suppression of ROS/NO/NF-қB signalling pathways

Vincristine (VCR), a vinca alkaloid with anti-tumor and anti-oxidant properties, is acclaimed to possess cardioprotective action. However, the molecular mechanism underlying this protective effect remains unknown. This study investigated the effects of VCR on isoprenaline (ISO), a beta-adrenergic receptor agonist, induced cardiac hypertrophy in male Wistar rats. Animals were pre-treated with ISO (1 mg/kg) intraperitoneally for 14 days before VCR (25 μg/kg) intraperitoneal injection from days 1 to 28. Thereafter, mechanical, and electrical activities of the hearts of the rats were measured using a non-invasive blood pressure monitor and an electrocardiograph, respectively. After which, the heart was homogenized, and supernatants were assayed for contractile proteins: endothelin-1, cardiac troponin-1, angiotensin-II, and creatine kinase-MB, with markers of oxidative/nitrergic stress (SOD, CAT, MDA, GSH, and NO), inflammation (TNF-a and IL-6, NF-kB), and caspase-3 indicative of VCR reduced elevated blood pressure and reversed the abnormal electrocardiogram. ISO-induced increased endothelin-1, cardiac troponin-1, angiotensin-II, and creatine phosphokinase-MB, which were reversed by VCR. ISO also increased TNF-α, IL-6, NF-kB expression with increased caspase-3-mediated apoptosis in the heart. However, VCR reduced ISO-induced inflammation and apoptosis, with improved endogenous antioxidant agents (GSH, SOD, CAT) relative to ISO controls. Moreso, VCR, protected against ISO-induced histoarchitectural degeneration of cardiac myofibre. The result of this study revealed that VCR treatment significantly reverses ISO-induced cardiac hypertrophic phenotypes, via mechanisms connected to improved levels of proteins involved in excitation-contraction, and suppression of oxido-inflammatory and apoptotic pathways.

Glutathione production by Saccharomyces cerevisiae: current state and perspectives.

Glutathione (L-γ-glutamyl-cysteinyl-glycine, GSH) is a tripeptide synthesized through consecutive enzymatic reactions. Among its several metabolic functions in cells, the main one is the potential to act as an endogenous antioxidant agent. GSH has been the focus of numerous studies not only due to its role in the redox status of biological systems but also due to its biotechnological characteristics. GSH is usually obtained by fermentation and shows a variety of applications by the pharmaceutical and food industry. Therefore, the search for new strategies to improve the production of GSH during fermentation is crucial. This mini review brings together recent papers regarding the principal parameters of the biotechnological production of GSH by Saccharomyces cerevisiae. In this context, aspects, such as the medium composition (amino acids, alternative raw materials) and the use of technological approaches (control of osmotic and pressure conditions, magnetic field (MF) application, fed-batch process) were considered, along with genetic engineering knowledge, trends, and challenges in viable GSH production. KEY POINTS: • Saccharomyces cerevisiae has shown potential for glutathione production. • Improved technological approaches increases glutathione production. • Genetic engineering in Saccharomyces cerevisiae improves glutathione production.

Antioxidant status of uric acid, bilirubin, albumin and creatinine during the acute phase after traumatic brain injury: sex-specific features

Background It is known that the alteration of antioxidants can been seen in early phase after traumatic brain injury (TBI) in order to block oxidative damage, but little is known about the influence of sex on antioxidant system in patients with TBI. This study investigates whether there are sex differences in these endogenous antioxidant agents during the acute phase after TBI and their association with the disease. Methods Serum levels of uric acid (UA), bilirubin, albumin and creatinine were measured in 421 individuals included 157 female TBI patients, 156 male TBI patients and 108 age- and sex-matched controls. Results The statistically significant changes were found in UA, bilirubin, albumin and creatinine for both sexes with TBI, but the trend of changes in bilirubin and creatinine was opposite for gender groups. Serum levels of UA, bilirubin, albumin and creatinine were associated with the severity of TBI patients for both sexes. Male patient subgroups with elevated UA, albumin and creatinine had higher frequency of regaining consciousness in a month. Moreover, addition of UA and creatinine to the established clinical model had significantly improved the predictive performance over using clinical model alone in male patients with TBI. However, no similar findings were observed on female TBI patients. Conclusion Our results suggest sex-based differences in the serum endogenous antioxidant response to TBI. Use of serum UA and creatinine could help in the outcome prediction of male patients with TBI in combination with other prognostic factors.

Effect of taurine on renal pathophysiology in Experimental animals

Taurine, an essential amino acid (2-amino ethanesulfonic acid) and endogenous antioxidant agent has been studied as an antioxidant agent in renal impairment however the efficacy is not very well documented and its impact on exogenous supplementation in normal renal physiology has conflicting results. Therefore the present study has been undertaken to evaluate the role of Taurine supplementation in normal physiology and impaired kidney status due to high dose Diclofenac in rat models. Albino rats were divided into groups of 4 animals each. Test I(Diclofenac only), Test II( Taurine only), Test III(Diclofenac + Taurine), Test IV(Diclofenac + Taurine + N-acetylcysteine). Diclofenac 13.5mg/kg bw/day i.m. given for 10 days. Taurine(7.5mg/kg/day) and N-acetycysteine(NAC(40 mg/kg) were given orally for 2 wks starting from day 5 of induced nephrotoxicity in respective groups. Serum urea and creatinine levels were measured after 1wk and 2wks of test drug administration and histopathological examination conducted. High dose of Diclofenac i.m. produced biochemical and histopathological features of nephrotoxicity. Biochemical and histopathological parameters also revealed features of nephrotoxicity in taurine only treated group. The group treated with Taurine + NAC for 2wks had significantly lowered nephrotoxic features compared to only Taurine treated group in nephrotoxic models.

Lycopene not in pill, nor in natura has photoprotective systemic effect

Carotenoids are endogenous antioxidant agents. It has been reported that oral lycopene reduces immediate erythema induced by ultraviolet B radiation. The objective was to evaluate and compare the photoprotective effect of lycopene in capsule and tomato paste. This was an interventional, randomized, comparative 10-week study that included 20 subjects, divided in two groups: 10 for capsule and 10 for tomato paste intake. Blood samples were collected for serum lycopene dosage by high-performance liquid chromatography. Chromatometer was used to measure minimal erythematous dose 24 h after only ultraviolet B irradiation and the variation of color a (maximum erythema, 24 h after irradiation compared to normal skin). Evaluations were made at baseline and after 4, 8, and 10 weeks. Data were analyzed by ANOVA with repeated measures. Three subjects dropped out after 4 weeks. Serum lycopene demonstrated great variability; significant, higher levels for tomato after 4 weeks (p = 0.027) as compared to capsule and significant increase along the study just for tomato (p = 0.044) were detected. No visual change for minimal erythematous dose was observed in all evaluations, for both groups. Chromatometer measures showed no difference in the mean of minimal erythematous dose at baseline between groups. Slight variation of color a after 10 weeks was observed [marginally significant (p = 0.054)], with a tendency to be greater for capsule use [marginally significant (p = 0.066)] and no adverse effects. Lycopene regular intake was safe and demonstrated no effect for systemic photoprotection against ultraviolet B; no correlation with serum lycopene was detected.

Signaling pathways involved in renal oxidative injury: role of the vasoactive peptides and the renal dopaminergic system.

The physiological hydroelectrolytic balance and the redox steady state in the kidney are accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Angiotensin II, atrial natriuretic peptide and intrarenal dopamine play a pivotal role in this interactive network. The balance between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide, by one side, and the prooxidant effect of the renin angiotensin system, by the other side, contributes to ensuring the normal function of the kidney. Different pathological scenarios, as nephrotic syndrome and hypertension, where renal sodium excretion is altered, are associated with an impaired interaction between two natriuretic systems as the renal dopaminergic system and atrial natriuretic peptide that may be involved in the pathogenesis of renal diseases. The aim of this review is to update and comment the most recent evidences about the intracellular pathways involved in the relationship between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide and the prooxidant effect of the renin angiotensin system in the pathogenesis of renal inflammation.

Melatonin replacement therapy in preterm infants: the impact of pharmacokinetics

Evaluation of: Merchant NM, Azzopardi DV, Hawwa AF et al. Pharmacokinetics of melatonin in preterm infants. Br. J. Clin. Pharmacol. doi: 10.1111/bcp.12092 (2013) (Epub ahead of print).The paper by Merchant et al. demonstrates that the pharmacokinetic profile of melatonin differs in preterm infants from that of adults. The findings of this study can guide the necessary future preventive and therapeutic clinical trials on melatonin in preterm infants. These studies are urgently needed to further evaluate the protective potential of melatonin in preterm infants. Melatonin acts as a potent endogenous antioxidant agent that antagonizes oxidative stress, and melatonin replacement therapy could thereby prevent the development of many disorders and diseases that can afflict preterm infants such as sepsis, asphyxia, respiratory distress or surgical complications. Since preterm infants are melatonin deficient, administration of the compound may provide the necessary levels to assure their health and well-being. Pharmacokinetic data such as those provided in the evaluated paper are necessary to establish safe and efficient melatonin treatment regimens in this highly susceptible population.

Gemfibrozil Pretreatment Affecting Antioxidant Defense System and Inflammatory, but not Nrf-2 Signaling Pathways Resulted in Female Neuroprotection and Male Neurotoxicity in the Rat Models of Global Cerebral Ischemia–Reperfusion

Two important pathophysiological mechanisms involved during cerebral ischemia are oxidative stress and inflammation. In pathological conditions such as brain ischemia the ability of free radicals production is greater than that of elimination by endogenous antioxidative systems, so brain is highly injured due to oxidation and neuroinflammation. Fibrates as peroxisome proliferator-activated receptor (PPAR)-α ligands, are reported to have antioxidant and anti-inflammatory actions. In this study, gemfibrozil, a fibrate is investigated for its therapeutic potential against global cerebral ischemia-reperfusion (I/R) injury of male and female rats. This study particularly has focused on inflammatory and antioxidant signaling pathways, such as nuclear factor erythroid-related factor (Nrf)-2, as well as the activity of some endogenous antioxidant agents. It was found that pretreatment of animals with gemfibrozil prior to I/R resulted in a sexually dimorphic outcome. Within females it proved to be protective, modulating inflammatory factors and inducing antioxidant defense system including superoxide dismutase (SOD), catalase, as well as glutathione level. However, Nrf-2 signaling pathway was not affected. It also decreased malondialdehyde level as an index of lipid peroxidation. In contrast, gemfibrozil pretreatment was toxic to males, enhancing the expression of inflammatory factors such as tumor necrosis factor-α, nuclear factor-κB, and cyclooxygenase-2, and decreasing Nrf-2 expression and SOD activity, leading to hippocampal neurodegeneration. Considering that gemfibrozil is a commonly used anti-hyperlipidemic agent in clinic, undoubtedly more investigations are crucial to exactly unravel its sex-dependent neuroprotective/neurodegenerative potential.

Glutathione S-Transferase M1 Gene Polymorphisms are Associated with Cardiac Iron Deposition in Patients with β-Thalassemia Major

Patients with β-thalassemia (thal) major are subject to peroxidative tissue injury by iron overload. Glutathione S-transferases work as antioxidants, and their activity is determined genetically. In this study, we used multiplex polymerase chain reaction (m-PCR) to analyze polymorphisms of two endogenous antioxidant agents, glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1), and to determine their roles in 41 patients with β-thal major. Our results showed that the GSTM1 and GSTT1 null genotypes were not associated with any incidence of endocrine dysfunction (including diabetes mellitus, hypogonadism, hypothyroidism, and growth hormone deficiency), liver function, or impaired left ventricular ejection fraction (LVEF). The GSTM1 null genotype, but not the GSTT1 null genotype, was associated with a decreased signal intensity ratio on cardiac magnetic resonance imaging (MRI). Our results suggest that genetic variations of the GSTM1 enzyme are associated with cardiac iron deposition in patients with β-thal major.

N‐Acetyldopamine Inhibits Rat Brain Lipid Peroxidation Induced by Lipopolysaccharide

The effects of N-acetyldopamine, a sepiapterin reductase inhibitor, on lipopolysaccharide-induced lipid peroxidation were examined in rat brain homogenates in vitro. Lipid peroxidation in the form of malondialdehyde (MDA) was evaluated by the measurement of thiobarbituric acid (TBA) reactive substances. N-Acetyldopamine inhibited the formation of MDA in a concentration-dependent manner. The effect was similar to that of N-acetylserotonin, but stronger than that of the endogenous antioxidant agent, melatonin. Possible clinical applications of N-acetyldopamine and its derivatives are discussed.

THE ANTIOXIDANT PROPERTIES OF TOBACCO

Mammalian cells have evolved a complex network of enzymatic and non-enzymatic molecules that protect them from the detrimental effects of reactive oxygen species (ROS). These endogenous antioxidant agents are supplemented by dietary antioxidants, obtained mainly from plants. Although many studies have assessed the antioxidant properties of fruits and vegetables, much less is known about the antioxidant characteristics of another commonly ingested plant product, tobacco. The antioxidant properties of 16 commercially available tobacco products were determined using an oxygen radical absorbance capacity (ORAC) assay. The concentrations of polyphenols in these products also were determined. The tobacco products tested had a range of antioxidant activity from modest to high. A significant linear relationship was observed between the overall antioxidant capacity and total phenolic content. The high antioxidant activity in smokeless tobacco may partially explain the low cancer risk associated with long-term use of these products.

Antioxidant properties of melatonin—an emerging mystery

Over three centuries ago, the French philosopher René Descartes described the pineal gland as “the seat of the soul.” However, it was not until the late 1950s that the chemical identity and biosynthesis of melatonin, the principal hormone secreted by the pineal body, were revealed. Melatonin, named from the Greek melanos, meaning black, and tonos, meaning color, is a biogenic amine with structural similarities to serotonin. The mechanisms mediating the synthesis of melatonin are transcriptionally regulated by the photoperiodic environment. Once synthesized, the neurohormone is a biologic modulator of mood, sleep, sexual behavior, reproductive alterations, immunologic function, and circadian rhythms. Moreover, melatonin exerts its regulatory roles through high-affinity, pertussis toxin-sensitive, G-protein (or guanine nucleotide binding protein) coupled receptors that reside primarily in the eye, kidney, gastrointestinal tract, blood vessels, and brain. Additional evidence also indicates a role for melatonin in aging and age-related diseases, probably related to its efficient free radical scavenger (or antioxidant) activity. The potential clinical benefit of melatonin as an antioxidant is remarkable, suggesting that it may be of use in the treatment of many pathophysiological disease states including various cancers, hypertension, pulmonary diseases, and a variety of neurodegenerative diseases such as Alzheimer’s disease. This review summarizes the biosynthesis of melatonin and its many endocrine and physiological functions, including its therapeutic potential in human disease states. Emphasis is placed on the recent speculations indicating that this pineal hormone serves as an endogenous antioxidant agent with proficient free radical scavenging activity.

Taurine ameliorates chronic streptozocin-induced diabetic nephropathy in rats.

We examined the effect of two endogenous antioxidant agents, taurine and vitamin E, on renal function in experimental diabetes. Male Sprague-Dawley rats, rendered diabetic with streptozocin (STZ), were assigned to one of the following groups: 1) untreated; 2) insulin treatment with 6 U Ultralente insulin/day in two doses; 3) taurine supplementation by 1% taurine in drinking water; and 4) vitamin E supplementation at 100 IU vitamin E/kg chow. Animals were kept for 52 wk. The survival rate was similar (70-90%) in all groups except vitamin E-treated animals, of which 84% died by 6 mo. At 52 wk, glomerular filtration rate was elevated in untreated and taurine-treated STZ rats compared with normal or insulin-treated diabetic rats. Taurine supplementation reduced total proteinuria and albuminuria by nearly 50%. This treatment also prevented glomerular hypertrophy, preserved immunohistochemical staining for type IV collagen in glomeruli, and diminished glomerulosclerosis and tubulointerstitial fibrosis in diabetic animals. The changes in renal function and structure in taurine-treated diabetic rats were associated with normalization of renal cortical malondialdehyde content, lowering of serum free Fe2+ concentration, and decreased formation of the advanced glycooxidation products, pentosidine, and fluorescence in skin collagen. Administration of the vitamin E-enriched diet exacerbated the nephropathy in STZ-diabetic rats. In addition, vitamin E supplementation increased serum free Fe2+ concentration, enhanced renal lipid peroxidation, and accelerated the accumulation of advanced glycosylation end products (AGEs) in skin collagen. We conclude that administration of taurine, but not vitamin E, to rats with STZ-diabetes ameliorates diabetic nephropathy. The beneficial effect of taurine is related to reduced renal oxidant injury with decreased lipid peroxidation and less accumulation of AGEs within the kidney.

Vitamin E Prevents Glucose-Induced Lipid Peroxidation and Increased Collagen Production in Cultured Rat Mesangial Cells

High glucose directly promotes lipid peroxidation and stimulates collagen production by cultured mesangial cells. We conducted the following experiments to ascertain whether vitamin E, a lipophilic antioxidant agent, could reverse these effects in vitro. Rat mesangial cells were grown to confluence and then maintained for 7 additional days in control media (DME) containing 5.6 m M glucose or experimental media containing 33.3 m M glucose. The test condition resulted in a near doubling of mesangial cell lipid peroxidations, assessed by measuring the content of conjugated dienes. High-glucose media also enchanced collagen production by 28% above the basal level in control media. Addition of mitamin E (100 μ M) reversed both effects of the elevated ambient glucose level and prevented lipid peroxidation and normalized collagen production in cultured mesangial cells. These findings sugggest that vitamin E functions as an endogenous antioxidant agent in the kidney to limit the development of glomerulosclerosis in diabetic nephropathy.