Detoxification Of Free Radicals Research Articles

Melatonin levels in the follicular fluids and its correlation with ICSI Outcomes

Background: Melatonin is a hormone mainly synthesized and secreted from the pineal gland. The daily rhythm of circulatory melatonin is released in very low concentrations during the day and high levels at night. Melatonin has many functions beside regulation of circadian rhythm including immune system and autonomic cardiovascular regulation but the main melatonin function is antioxidant action and detoxification of free radicals. Patients and method: This cross sectional study was conducted during the period starting from November 2018 to May 2019. Eighty infertile female aged range 18–46 years were enrolled in the present study, the patients were undergoing controlled ovarian induction for IVF /ICSI treatment. All patents were divided into 3 groups according to age, FSH, E2, AMH and ovarian respond to controlled ovarian stimulation (COS) protocols. The follicular fluid melatonin measured at oocyte retrieval day using enzyme linked immunosorbent assay (ELISA). Results: There was significant difference in follicular fluid melatonin level between the three studied groups (p=0.031). There was also a positive significant correlation between follicular fluid melatonin with MII oocytes (r=0.343; p= 0.024), grade I embryo (r=0.375; p= 0.003) and AMH (r = 0.279; p= 0.027), on the other hand there was a negative significant correlation between follicular fluid melatonin and serum FSH (r = - 0.331; p= 0.016). There was also no significant difference of follicular fluid melatonin levels between pregnant and non-pregnant females (p=0.083). Conclusion: Melatonin levels in follicular fluid improve the oocytes and embryo qualities but have no effect in positive pregnancy rate.

Water‐Dispersible BODIPY Multifunctionalized Silicon Oxide Nanoparticles for Glutathione Sensing

AbstractGlutathione (GSH), a thiol containing small peptide, plays pivotal roles in maintaining cellular redox balance, metabolism, detoxification, and scavenging of free radicals. Aberrant GSH levels in cells and tissues are associated with various disorders, underscoring the importance of accurate GSH detection for clinical diagnosis and therapy monitoring. Several molecular probes have been designed as fluorescent‐based GSH sensors. However, their water insolubility and the need of using organic cosolvents hinder their applicability on biological samples. Alternatively, nanomaterials have proven to be highly promising for boosting the precision of treatments and enhancing the accuracy of diagnosing diseases, thanks to their compatibility with biological environments and improved cell uptake. Here, the synthesis and characterization of a boron‐dipyrromethene (BODIPY)‐based probe (PB) are reported, incorporating a fluorescent BODIPY core, chlorine substituents for reaction with GSH, and a linking moiety for conjugation to the surface of silicon oxide nanoparticles (SONPs). Functionalized SONPs with PB are also characterized at the nanoscale using high‐resolution transmission electron microscopy (HR‐TEM), dynamic light scattering (DLS), Zeta potential, Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), UV–Vis absorption, and fluorescence spectroscopies, confirming the surface functionalization and water‐dispersibility of functionalized SONPs with PB. GSH sensing is evaluated in aqueous solution, conjugated to SONPs, and in living cells, showing promising potential for ratiometric GSH detection.

Role of trace minerals in bull reproductive physiology and semen quality

Testicular dysfunction is often associated with an imbalance in antioxidant/oxidant homeostasis, leading to negative effects of oxidative stress on germ cell proliferation, steroidogenesis, and sperm function. Trace minerals (TM) are involved in basic homeostatic and enzymatic processes like free radical detoxification, cellular respiration, carbohydrates, lipids, nucleic acids, synthesis and metabolism of proteins, and stabilization of membranes and DNA. Dietary source of TM is necessary to support these processes. Supplementing cattle with TM is nowadays a common practice to help support growth, reproduction, and immunity. This review provides information on roles of TM in bulls testicular and sperm functions, and effects of TM mineral supplementation on bull reproductive parameters.

A near-infrared fluorescent probe with two-photon excitation for in situ imaging of NQO1 in human colorectum cancer tissue

Colorectum cancer has become one of the most fatal cancer diseases, in which NAD(P)H: quinone oxidoreductase 1 (NQO1) plays a role in intracellular free radical reduction and detoxification and has been linked to colorectum cancer and chemotherapy resistance. Therefore, rational design of optical probe for NQO1 detection is urgent for the early diagnosis of colorectum cancer. Herein, we have developed a novel two-photon fluorescent probe, WHFD, which is capable of selectively detecting of intracellular NQO1 with two-photon (TP) absorption (800 nm) and near-infrared emission (620 nm). Combination with a substantial Stokes shift (175 nm) and biocompatibility, we have assessed its suitability for in vivo imaging of endogenous NQO1 activities from HepG2 tumor-bearing live animals with high tissue penetration up to 300 μm. Particularly, we for the first time used the probe to image NQO1 activities from human colorectum cancer samples by using TP microscopy, and proving our probe possesses reliable diagnostic performance to directly in situ imaging of cancer biomarker and can clearly distinguish the boundary between human colorectum cancer tissue and their surrounding normal tissue, which shows great potential for the intraoperative navigation.

Polymorphism of Free Radicals Detoxification Genes GSTM1 and GSTT1 is Associated to Prostate Cancer Risk in men: Case Study in Benin

Polymorphism of Free Radicals Detoxification Genes GSTM1 and GSTT1 is Associated to Prostate Cancer Risk in men: Case Study in Benin

The pentose phosphate pathway in health and disease.

The pentose phosphate pathway (PPP) is a glucose-oxidizing pathway that runs in parallel to upper glycolysis to produce ribose 5-phosphate and nicotinamide adenine dinucleotide phosphate (NADPH). Ribose 5-phosphate is used for nucleotide synthesis, while NADPH is involved in redox homoeostasis as well as in promoting biosynthetic processes, such as the synthesis of tetrahydrofolate, deoxyribonucleotides, proline, fatty acids and cholesterol. Through NADPH, the PPP plays a critical role in suppressing oxidative stress, including in certain cancers, in which PPP inhibition may be therapeutically useful. Conversely, PPP-derived NADPH also supports purposeful cellular generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) for signalling and pathogen killing. Genetic deficiencies in the PPP occur relatively commonly in the committed pathway enzyme glucose-6-phosphate dehydrogenase (G6PD). G6PD deficiency typically manifests as haemolytic anaemia due to red cell oxidative damage but, in severe cases, also results in infections due to lack of leucocyte oxidative burst, highlighting the dual redox roles of the pathway in free radical production and detoxification. This Review discusses the PPP in mammals, covering its roles in biochemistry, physiology and disease.

Cellular Compartmentalization, Glutathione Transport and Its Relevance in Some Pathologies.

Reduced glutathione (GSH) is the most abundant non-protein endogenous thiol. It is a ubiquitous molecule produced in most organs, but its synthesis is predominantly in the liver, the tissue in charge of storing and distributing it. GSH is involved in the detoxification of free radicals, peroxides and xenobiotics (drugs, pollutants, carcinogens, etc.), protects biological membranes from lipid peroxidation, and is an important regulator of cell homeostasis, since it participates in signaling redox, regulation of the synthesis and degradation of proteins (S-glutathionylation), signal transduction, various apoptotic processes, gene expression, cell proliferation, DNA and RNA synthesis, etc. GSH transport is a vital step in cellular homeostasis supported by the liver through providing extrahepatic organs (such as the kidney, lung, intestine, and brain, among others) with the said antioxidant. The wide range of functions within the cell in which glutathione is involved shows that glutathione's role in cellular homeostasis goes beyond being a simple antioxidant agent; therefore, the importance of this tripeptide needs to be reassessed from a broader metabolic perspective.

Regulatory roles of copper metabolism and cuproptosis in human cancers.

Copper is an essential micronutrient for human body and plays a vital role in various biological processes including cellular respiration and free radical detoxification. Generally, copper metabolism in the body is in a stable state, and there are specific mechanisms to regulate copper metabolism and maintain copper homeostasis. Dysregulation of copper metabolism may have a great connection with various types of diseases, such as Wilson disease causing copper overload and Menkes disease causing copper deficiency. Cancer presents high mortality rates in the world due to the unlimited proliferation potential, apoptosis escape and immune escape properties to induce organ failure. Copper is thought to have a great connection with cancer, such as elevated levels in cancer tissue and serum. Copper also affects tumor progression by affecting angiogenesis, metastasis and other processes. Notably, cuproptosis is a novel form of cell death that may provide novel targeting strategies for developing cancer therapy. Copper chelators and copper ionophores are two copper coordinating compounds for the treatment of cancer. This review will explore the relationship between copper metabolism and cancers, and clarify copper metabolism and cuproptosis for cancer targeted therapy.

Oxidative Stress: Glutathione and Its Potential to Protect Methionine-35 of Aβ Peptide from Oxidation.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder with heterogeneous etiology. Intracellular neurofibrillary tangles caused by tau (τ) protein phosphorylation and extracellular senile plaques caused by aggregation of amyloid-beta (Aβ) peptide are characteristic histopathological hallmarks of AD. Oxidative stress (OS) is also suggested to play a role in the pathophysiology of AD. The antioxidant glutathione (GSH) is able to mitigate OS through the detoxification of free radicals. The clearance of these free radicals is reported to be affected when there is a decline in GSH levels in AD. These radicals further react with the methionine-35 (M-35) residue of Aβ and facilitate its subsequent oligomerization. This review presents a plausible model indicating the role of master antioxidant GSH to protect M35 of Aβ1–40/Aβ1–42 from oxidation in pathological conditions as compared to healthy controls.

Deficiency in glutathione synthesis and reduction contributes to the pathogenesis of colitis-related liver injury.

Liver disease is the most common extra-intestinal manifestation of ulcerative colitis (UC), but the underlying pathogenesis is still not clarified. It is well accepted that the occurrence of UC-related liver disease has close correlation with immune activation, intestinal bacterial liver translocation, inflammatory cytokine storm, and the disturbance of bile acid circulation. The occurrence of UC-related liver disease makes the therapy difficult, therefor study on the pathogenesis of UC-related liver injury is of great significance for its prevention and treatment. Glutathione (GSH) shows multiple physiological activities, such as free radical scavenging, detoxification metabolism and immune defense. The synthesis and the oxidation-reduction all contribute to GSH antioxidant function. It is reported that the deficiency in hepatic GSH antioxidant function participates in multiple liver diseases, but whether it participates in the pathogenesis of UC-related liver injury is still not clear. This study aims to investigate the feature and underlying mechanism of GSH synthesis and oxidation-reduction function during the development of UC, which will provide useful information for the pathogenesis study on UC-related liver injury. UC model was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS)-ethanol solution (5 mg/0.8 mL per rat, 50% ethanol) via intra-colonic administration in rats, and the samples of serum, liver, and colon tissue of rats were collected at the 3rd, 5th, and 7th days post TNBS. The severity degree of colitis was evaluated by measuring the disease activity index, colonic myeloperoxidase activity, and histopathological score, and the degree of liver injury was evaluated by histopathological score and the serum content of alanine aminotransferase. Spearman correlation analysis was also conducted between the degree of colonic lesions and index of hepatic histopathological score as well as serum aspartate aminotransferase level to clarify the correlation between liver injury and colitis. To evaluate the hepatic antioxidant function of GSH in UC rats, hepatic GSH content, enzyme activity of GSH peroxidase (GSH-Px), and GSH reductase (GR) were determined in rats at the 3rd, 5th, and 7th days post TNBS, and the protein expressions of glutamine cysteine ligase (GCL), GSH synthase, GSH-Px, and GR in the liver of UC rats were also examined by Western blotting. Compared with the control, the disease activity index, colonic myeloperoxidase activity, and histopathological score were all significantly increased at the 3rd, 5th, and 7th days post TNBS (all P<0.01), the serum aspartate aminotransferase level and hepatic histopathologic score were also obviously elevated at the 7th day post TNBS (all P<0.05). There was a significant positive correlation between the degree of liver injury and the severity of colonic lesions (P=0.000 1). Moreover, compared with the control, hepatic GSH content and the activity of GSH-Px and GR were all significantly decreased at the 3rd and 5th days post TNBS (P<0.05 or P<0.01), and the protein expressions of GCL, GSH-Px, and GR were all obviously down-regulated at the 3rd, 5th, and 7th days post TNBS (P<0.05 or P<0.01). There is a significant positive correlation between the degree of liver injury and the severity of colonic lesions, and the occurrence of reduced hepatic GSH synthesis and decreased GSH reduction function is obviously earlier than that of the liver injury in UC rats. The reduced hepatic expression of enzymes that responsible for GSH synthesis and reduction may contribute to the deficiency of GSH synthesis and oxidation-reduction function, indicating that the deficiency in GSH antioxidant function may participate in the pathogenesis of UC related liver injury.

Melatonin and Microglia

Melatonin interacts in multiple ways with microglia, both directly and, via routes of crosstalk with astrocytes and neurons, indirectly. These effects of melatonin are of relevance in terms of antioxidative protection, not only concerning free-radical detoxification, but also in prevention of processes that cause, promote, or propagate oxidative stress and neurodegeneration, such as overexcitation, toxicological insults, viral and bacterial infections, and sterile inflammation of different grades. The immunological interplay in the CNS, with microglia playing a central role, is of high complexity and includes signaling toward endothelial cells and other leukocytes by cytokines, chemokines, nitric oxide, and eikosanoids. Melatonin interferes with these processes in multiple signaling routes and steps. In addition to canonical signal transduction by MT1 and MT2 melatonin receptors, secondary and tertiary signaling is of relevance and has to be considered, e.g., via the upregulation of sirtuins and the modulation of pro- and anti-inflammatory microRNAs. Many details concerning the modulation of macrophage functionality by melatonin are obviously also applicable to microglial cells. Of particular interest is the polarization toward M2 subtypes instead of M1, i.e., in favor of being anti-inflammatory at the expense of proinflammatory activities, which is well-documented in macrophages but also applies to microglia.

ALPHA-GST AS A TUBULAR BIOMARKER IN EARLY DIAGNOSIS OF ACUTE KIDNEY INJURY IN CARDIAC SURGERY

Objective: Acute Kidney Injury(AKI) is a frequent complication in cardiac surgery, leading to an increase in morbility/mortality. The monitorization of the creatinine after the procedure is recommended, however, new tubular biomarkers may allow earlier diagnosis of AKI(a few hours after the procedure, against the 24/48 hours standard). Glutathione S-transferase(GST), cytoplasmic enzymes involved in detoxification of free radicals, are presented in the proximal contoured tube. The aim of this study is to evaluate the use of a single alpha-GST determination at 3 h after surgery, to early diagnosis of AKI. Design and method: Cohort, prospective and observational study, with adults submitted to elective cardiac surgery (valvular/coronary), without chronic kidney disease. Blood and urine samples were collected simultaneously before(T0) and within 3 hours after surgery(T1). The levels of alpha-GST were determined in the urine samples by ELISA and normalized to urinary creatinine(UCr). The variation of alpha-GST was calculated using the difference between T1 and T0(T1-T0). Demographic, clinical and surgical-related data was collected. For statistical analysis, Chi-square and Mann-Whitney test were used. The ROC curve was generated in order to evaluate the discriminative power of the biomarker. P &lt; 0.05 was statistically significant. Results: This study included 17 patients(11 male and 6 female), with 88.2% submitted to valvular surgery, with a mean age of 63.4 ± 14.3 years. Before the procedure, 82.4% of the patients had hypertension. After 48 hours surgery, using as gold standard the KDIGO classification, 6 patients presented AKI stage 1(75%) and 2(25%) stage 2. The mean arterial blood pressure was higher before surgery(T0: 90.0[74.5–103.3] vs T1: 64.5[57.2–80.7], p = 0.05). The increase of alpha-GST levels were associated to presence of AKI(p = 0.05). This increase remains when associated with the variation of alpha-GST(T1-T0) without and with AKI (- 0,002[-0.02–0.004]vs -0.02[0.009–0.04], respectively, p = 0.003). In the ROC curve, this variation had a AUC = 0.958(p = 0.05) and AUC = 0.854(p = 0.028) for the cut-off of the alpha-GST variation. These biomarkers present 78%-specificity and 75%-sensibility. Conclusions: alpha-GST is a promising biomarker to the early diagnosis of AKI after cardiac surgery with only one determination, contributing to this diagnosis before an increase of serum creatinine. Preventing costs and therapeutic options.

Divergent Importance of Chronobiological Considerations in High- and Low-dose Melatonin Therapies.

Melatonin has been used preclinically and clinically for different purposes. Some applications are related to readjustment of circadian oscillators, others use doses that exceed the saturation of melatonin receptors MT1 and MT2 and are unsuitable for chronobiological purposes. Conditions are outlined for appropriately applying melatonin as a chronobiotic or for protective actions at elevated levels. Circadian readjustments require doses in the lower mg range, according to receptor affinities. However, this needs consideration of the phase response curve, which contains a silent zone, a delay part, a transition point and an advance part. Notably, the dim light melatonin onset (DLMO) is found in the silent zone. In this specific phase, melatonin can induce sleep onset, but does not shift the circadian master clock. Although sleep onset is also under circadian control, sleep and circadian susceptibility are dissociated at this point. Other limits of soporific effects concern dose, duration of action and poor individual responses. The use of high melatonin doses, up to several hundred mg, for purposes of antioxidative and anti-inflammatory protection, especially in sepsis and viral diseases, have to be seen in the context of melatonin’s tissue levels, its formation in mitochondria, and detoxification of free radicals.

Evaluation of Biochemical, Hematological and Antioxidant Properties in Mice Exposed to a Triherbal (&amp;lt;i&amp;gt;Nigella sativa, Carica papaya and Boswellia sacra&amp;lt;/i&amp;gt;) Formular

Nigella sativa, Carica papaya and Boswellia sacra are medicinal plants in the commonly used in folkloric medicine due to the presence of its immense therapeutic properties. Fifty (50) female albino mice weighing between 15-22g were divided into five groups of 10 mice each. Animal in group 1 served as control group and were administered distilled water while animal in group 2 were given 2ml of cisplatin (orally). Animal in group 3-5 were given orally; 100 mg/kg (low dose), 200 mg/kg (medium dose) and 400 mg/kg (high dose) of triherbal preparation. The feeding regimens lasted for 28 days. After 28 days, mammary gland and blood samples were collected for haematological and antioxidant analysis. The triherbal formula decreased the GSH and MDA levels of mice treated with 100 mg/kg and 400 mg/kg doses compare to control. The measurement of total protein content, SOD and CAT increased in treated animals compared to control. However, RBC (Red Blood Cell) counts significantly decreased in the low, medium and high dose groups (0.95±0.08, 6.57±0.08 and 3.55±0.55 x 106 cells/mm3 respectively) compared to control (7.34±0.40) at P<0.05. Also, significant decreases (P<0.05) in the level of the total WBC (White Blood Cell) count, platelet count, PCV (Packed Cell Volume) and Hb (haemoglobin) concentration were observed. The decreases were dose dependent. The MCH (Mean Corpuscular Haemoglobin) and MCHC (Mean Corpuscular Haemoglobin Concentration) except MCV (Mean Corpuscular Volume) significantly decreased in treated group only. The triherbal formulation exhibited significant antioxidant activities showing increased levels of SOD, CAT and Protein content due to activation of the enzyme involve in detoxification of free radicals and decreased in the level of GSH and MDA due to accumulation of peroxides and H2O2. Also, decreased in haematological parameters due to the presence of phytochemicals such as phenol, resins, saponins, sterols, tannis and terpenes in the triherbal formula. Therefore, it has potential to induce haematotoxicity hence consumption of high concentrations should be discouraged.

Radioprotective Role of Natural Polyphenols: From Sources to Mechanisms.

The identification and development of radioprotective agents have emerged as a subject matter of research during recent years due to the growing usage of ionizing radiation in different areas of human life. Previous work on synthetic radioprotectors has achieved limited progress because of the numerous issues associated with toxicity. Compounds extracted from plants have the potential to serve as lead candidates for developing ideal radioprotectors due to their low cost, safety, and selectivity. Polyphenols are the most abundant and commonly dispersed group of biologically active molecules possessing a broad range of pharmacological activities. Polyphenols have displayed efficacy for radioprotection during various investigations and can be administered at high doses with lesser toxicity. Detoxification of free radicals, modulating inflammatory responses, DNA repair, stimulation of hematopoietic recovery, and immune functions are the main mechanisms for radiation protection with polyphenols. Epicatechin, epigallocatechin-3-gallate, apigenin, caffeic acid phenylethylester, and silibinin provide cytoprotection together with the suppression of many pro-inflammatory cytokines owing to their free radical scavenging, anti-oxidant, and anti-inflammatory properties. Curcumin, resveratrol, quercetin, gallic acid, and rutin's radioprotective properties are regulated primarily by the direct or indirect decline in cellular stress. Thus, polyphenols may serve as potential candidates for radioprotection in the near future; however, extensive investigations are still required to better understand their protection mechanisms.

Revisiting the metallothionein genes polymorphisms and the risk of oral squamous cell carcinoma in a Brazilian population.

Background Metallothioneins (MTs) gene polymorphisms have been associated with the ability of free radical scavenging and detoxification of heavy metals leading to cancer development. Our aim was to revisit, in a Brazilian population, single-nucleotide polymorphisms (SNPs) of the MT gene family previously associated with oral squamous cell carcinoma (OSCC). Material and Methods A case-control investigation with 28 OSCC patients and 45 controls was conducted, using conventional risk factors (tobacco use and alcohol consumption) as covariates. SNPs genotyping for rs8052334 (MT1B), rs964372 (MT1B), and rs1610216 (MT2A) was performed by PCR-RFLP, and SNPs for rs11076161 (MT1A) were analyzed by TaqMan assay. Results The only SNP associated with increased risk for OSCC was the MT-1A AA genotype (OR = 4.7; p = 0.01). We have also evidenced for the first time a significant linkage disequilibrium between the SNPs of MT-2A and MT-1A in this population with the highest frequency (30%) of the unfavorable haplotype G/A/C/T (rs1610216 / rs11076161 / rs964372 / rs8052334) of MT gene polymorphisms (OR = 6.2; p = 0.04). Interestingly, after removing the effects of conventional risk factors, we have uncovered the significance of the AA genotype of the rs11076161 with increased odds of 19-fold higher towards OSCC development. Conclusions This is the first demonstration that a significant linkage disequilibrium among gene polymorphisms of the MT family may affect susceptibility to oral cancer, which is conditioned by the G/A/C/T haplotype (rs1610216/rs11076161/rs964372/ rs8052334) and the MT-1A gene polymorphism has a potential clinical utility for the OSCC risk assessment. Key words:Oral squamous cell carcinoma, polymorphism, metallothionein, oral cancer.

27 Shotgun proteomics reveal seminal plasma proteomes are reflective of boar reproductive performance

Abstract Subfertile boars have a negative economic impact for producers and need to be identified before they enter the breeding herd. Current semen evaluation techniques are not able to identify all subfertile boars. Seminal plasma proteins are essential for normal sperm function and transport and play an important role in fertilization. We hypothesize that seminal plasma proteins affect fertility, and thus differences in protein profiles reflect differences in boar fertility. The objective of this study was to use LC-MS/MS for shotgun proteome analysis to investigate whether differences in boar fertility phenotype can be differentiated by seminal plasma protein expression. Following 50 single-sire matings, boars were categorized into one of four phenotypes: high farrowing rate and high total born (HFHB; n=9), high farrowing rate with low total born (HFLB; n=10), low farrowing rate and low total born (LFLB; n=9), and low farrowing rate with high total born (LFHB; n=4). There were 436 proteins measured in at least one sample across all animals. There were 245 high confidence proteins and 56 were differentially abundant (P &amp;lt; 0.05) between the high fertility phenotype (HFHB) and at least one of the three subfertile groups. Proteins associated with fertility and free radical detoxification were more abundant in HFHB whereas subfertile phenotypes had a greater abundance of blood microparticle proteins, biomarkers of inflammation, and IMPA1, which regulates inositol production. Findings support that seminal plasma protein profiles are distinct between boars with different fertility phenotypes and have the potential to predict boar reproductive performance.

Hydroxyl radical scavenging activity of melatonin and its related indolamines

The hydroxyl radical (•OH) scavenging activities of Melatonin, an endogenously produced neurohormone and its related indolamines like N-acetyl tryptophan (NAT) and N-acetyl serotonin (NAS) have been investigated using density functional theory. The mechanism involves 4 steps: initial radical addition to position-3 of the indole ring, keto-amine to enol-imine tautomerization, cyclisation, and finally, addition of a second •OH leading to a cyclic end product. Incorporation of an explicit water molecule in tautomerization step leads to a significant reduction in the barrier of this step, so that the subsequent cyclisation step becomes rate-limiting. In agreement with the very high reactivity of •OH, the initial and final addition of •OH to indolamine are found to be barrierless. Radical adduct formed in the initial step was found to be very stable due to the extensive conjugation present in the substrate. Our calculations show that melatonin is the most effective radical scavenger among the three molecules chosen. NAS was found to exhibit antiradical property comparable to that of melatonin. In contrast to the general observation of reduced antioxidant activity of tryptophan, a non-natural derivative of tryptophan used here (NAT) is found to have good radical scavenging activity. This work further implies that non-natural derivatives of indolamines might as well be useful in the detoxification of free radicals as they exhibit almost comparable antioxidant efficiency as that of melatonin.

Purification of Glutathione Reductase from Human Erythrocytes: Inhibition Profile of Some Anti-Epileptic Drugs

Glutathione reductase (GR) is found in the NADPH-dependent oxidoreductase family. GR has various important functions in the cell, such as protein and DNA biosynthesis, the detoxification of reactive oxygen species and free radicals. The purpose of this research was to perform the in vitro inhibition effects of anti-epileptic drugs (phenytoin, gabapentin, and primidone) on GR enzyme. In the current study, the GR enzyme was purified from human erythrocytes with a specific activity of 20.08 EU/mg protein and 2135.97-purification fold. To determine the inhibition effects of anti-epileptic drugs on GR enzyme, Lineweaver-Burk graphs were drawn for each inhibitor. Ki values and inhibition types were determined from these plotted graphs. The Ki values of drugs were found in ranging from 0.15± 0.03-5.74±1.14 mM. Phenytoin was shown the most effective inhibitor feature with a competitive inhibition type.

Serum antioxidant status and some selected trace metal levels in patients with cervical intraepithelial neoplasm in Benin City, Nigeria

Antioxidants are important in the detoxification of free radicals, which are the hazardous derivatives of metabolic processes in the body. However, the mop up of free radicals in the prevention and management of cervical intraepithelial neoplasm is not clear. This study presented an assessment of the status of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), total antioxidant capacity (TAC) and some trace metals (Ca, Mg, Cu and Zn) in women diagnosed with Cervical Intraepithelial Neoplasm (CIN) lesions. The study was carried out at the Department of Obstetrics and Gynaecology, University of Benin Teaching Hospital Benin City and Department of Chemical Pathology, Edo University Iyamho, Edo state Nigeria. Study participants were grouped into two; those with CIN lesions (n = 144) and the control (n = 53). Venous blood was obtained from participants and serum antioxidant levels were determined using standardized laboratory methods. Results showed that CAT levels increased significantly from 23.88 u/μl/min in the control group to 31.79 u/μl/min in CIN. The incidence of cervical intraepithelial neoplasm lesions did not significantly affect total antioxidant capacity (TAC) of the study population (2.43 - 2.70 mM, P>0.05). There were minimal increases in antioxidant status between the control and CIN groups respectively (P> 0.05). Cu was implicated as the only trace metal within the CIN group without significant correlation to the antioxidants investigated. Keywords: Epithelial cell, cervical cancer, neoplasm, antioxidant status