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Antioxidants in the prevention and treatment of alzheimer’s disease
(Springer International Publishing, 2018) Sandeep Kumar Singh; Saripella Srikrishna; Rudy J. Castellani; George Perry
Alzheimer’s disease (AD) is the most common human neurodegenerative disease that causes dementia in the elderly. A person suffering with AD shows gradual memory deterioration and other cognitive discrepancies, which eventually lead to complete incapacity and ultimately death. The major pathological characteristics of AD are the presence of senile plaques extracellularly and neurofibrillary tangles intracellularly. Growing evidences have demonstrated that oxidative stress is an important factor contributing to the initiation and progression of AD. However, the exact mechanisms that lead to the disruption of redox balance and the sources of free radicals remain elusive. The excessive reactive oxygen species may be generated from mechanisms such as mitochondrial dysfunction and/or aberrant accumulation of transition metals, while the abnormal accumulation of amyloid-β protein (Aβ) and tau proteins appears to promote redox imbalance. The resulting oxidative stress has been implicated in Aβ or tau-induced neurotoxicity. To combat oxidative stress in AD, antioxidants have been therapeutically implicated. Within the last few years, a number of polyphenolic compounds with antioxidant and neuroprotective effects have been described to possibly benefit AD patients. Many efforts have been made to explore the mechanisms behind the neuroprotective action of polyphenols. The aim of this chapter is to critically review the use of different types of antioxidants in the prevention and treatment of AD. © Springer International Publishing AG 2017.
Maternal BDE-209 exposure during lactation causes testicular and epididymal toxicity through increased oxidative stress in peripubertal mice offspring
(Elsevier Ireland Ltd, 2019) Debarshi Sarkar; Deepanshu Joshi; Shio Kumar Singh
Decabromodiphenyl ether (BDE-209), a flame retardant, interferes with thyroid homeostasis and androgen biosynthesis. BDE-209 evokes hyperglycemia through impaired glucose homeostasis in rat liver. This study is in continuation to our earlier work for a better understanding of whether or not BDE-209 affects testicular and epididymal physiology in relation to oxidative status in peripupertal mice offspring. Lactating female Parkes mice were orally gavaged with 500 and 700 mg/kg body weight of BDE-209 in corn oil from postnatal day (PND)1 to PND 28. Male pups of lactating dams were sacrificed at PND 42. Maternal BDE-209 exposure during lactation increased apoptosis and oxidative status with altered expressions of various cell survival (Bcl-2), apoptotic (Bax and caspase-3)and oxidative stress (Nrf2 and HO-1)markers in testes and epididymis of peripubertal mice offspring. Testicular glucose and lactate concentrations were markedly reduced in these pups with down-regulation in GLUT3 and GLUT8 expressions and decreased LDH activity. Maternal BDE-209 exposure markedly affected fertility potential, epididymal histology, sialic acid concentration and sperm quality with decreased expression of epididymal Cx43 and AR in these mice offspring. Results thus suggest that maternal BDE-209 exposure during lactation causes reproductive toxicity in peripubertal mice offspring. © 2019 Elsevier B.V.
Arsenite and arsenate impact the oxidative status and antioxidant responses in Ocimum tenuiflorum L
(Springer India, 2015) Fauzia Siddiqui; P.K. Tandon; Sudhakar Srivastava
Biochemical responses of Ocimum tenuiflorum plants were studied upon exposure to arsenite (AsIII) and arsenate (AsV) for 1 to 10 d. Plants accumulated significant amounts of As in leaves (662 μg g−1 dry weight; DW and 412 μg g−1 DW in response to 100 μM AsIII and AsV exposure, respectively after 10 d). Consequently, fresh weight and growth of plants declined in a concentration dependent manner. Further, total chlorophyll and carotenoid contents also declined while oxidative stress markers increased, particularly on longer durations. Various antioxidant enzymes and thiols (cysteine and glutathione; GSH) showed significant and variable increases upon exposure to AsV and AsIII with the response being comparatively better in response to AsV. Proline increased significantly upon exposure to both AsIII and AsV. Plants thus tolerated high As concentrations through induced antioxidant machinery. © 2015, Prof. H.S. Srivastava Foundation for Science and Society.
Ecotoxicological impacts of environmentally relevant concentrations of aspirin in the liver of Labeo rohita: Biochemical and histopathological investigation
(Elsevier Ltd, 2023) Tuhina Gayen; Anchal Tripathi; Usha Kumari; Swati Mittal; Ajay Kumar Mittal
Aspirin is one of the emerging pharmaceutical contaminants in the aquatic environment and thus it could impart toxicity to non-target organisms including fish. The present study aims to investigate the biochemical and histopathological alterations in the liver of the fish, Labeo rohita exposed to environmentally relevant concentrations of aspirin (1, 10, and 100 μg/L) for 7, 14, 21, and 28 days. The biochemical investigation revealed a significant (p < 0.05) decrease in the activity of antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase; and reduced glutathione content in a concentration and duration dependent manner. Further, the decrease in the activity of superoxide dismutase was in a dose dependent manner. The activity of glutathione-s-transferase, however, increased significantly (p < 0.05) in a dose dependent manner. The lipid peroxidation and total nitrate content showed a significant (p < 0.05) increase in a dose and duration dependent manner. The metabolic enzymes such as acid phosphatase, alkaline phosphatase, and lactate dehydrogenase showed a significant (p < 0.05) increase in all three exposure concentrations and durations. The histopathological alterations in the liver such as vacuolization, hypertrophy of the hepatocytes, nuclear degenerative changes, and bile stagnosis increased in a dose and duration dependent manner. Hence, the present study concludes aspirin has a toxic impact on fish, which is evidenced by its profound effect on biochemical parameters and histopathological analysis. These can be employed as potential indicators of pharmaceutical toxicity in the field of environmental biomonitoring. © 2023 Elsevier Ltd
Seed priming with Mg(NO3)2 and ZnSO4 salts triggers physio-biochemical and antioxidant defense to induce water stress adaptation in wheat (Triticum aestivum L.)
(Elsevier B.V., 2021) Rajesh Kumar Singhal; Saurabh Pandey; Bandana Bose
Wheat is a widely grown cereal crop that provides >20% daily protein intake and calories worldwide. Drought stress drastically affects the crucial physiological (relative water content; RWC), biochemical (proline content), and molecular attributes in wheat plants from germination to maturity stage and ultimately reduces the yield and quality traits. Given this, the present work was conducted to know the effect of salt seed priming on wheat crop. For this, we have used two wheat variety HUW-468 (V1), and HUW-510 (V2) primed with water (T2), Mg(NO3)2 (T3), ZnSO4 (T4), and combinations of Mg(NO3)2 and ZnSO4 salt (T5) with non-primed seed (T1) under water stress (W1) and control (W0) conditions. We have observed significant differences in plant height (84 to 90 cm), leaf number, total leaf area (431.82 to 505.46 cm2 plant−1), relative water content, chlorophyll content (4.78 to 5.86 mg g−1fresh weight), membrane stability index (MSI) (56.25 to 61.42%), superoxide dismutase (SOD) activity (133.47 to 150.10), MDA content, proline content (101.64 to 100.46), nitrate reductase activity (NRA), and nutrient (N, Zn, and Fe) contents under control and stress conditions. These results concluded that seed priming with a combination of Mg(NO3)2 and ZnSO4 salt is best for improved wheat crop traits under drought stress compared to individual salt and non-priming treatments. Overall, this analysis elucidated that seed priming strengthens the antioxidant capacity under drought conditions by enhancing antioxidant enzymes and alleviating oxidative stress. © 2021 The Author(s)
A study of oxidative stress in cervical cancer- an institutional study
(Elsevier B.V., 2021) Kulsoom Zahra; Sandeep Patel; Tulika Dey; Uma Pandey; Surendra Pratap Mishra
Cervical cancer is the second most common cause of cancer-related death among women worldwide, especially in developing countries. Oxidative stress has been associated with cervical cancer. Many studies demonstrated that the low level of antioxidants induces the production of free radicals that cause lipid peroxidation, DNA, and protein damage leading to mutations that favors malignant transformation. This is a case-control institutional study conducted to evaluate the level of oxidative stress in cervical cancer patients and the age-matched healthy controls. We measured level of TBARS expressed as MDA, activity of SOD and GSH level by the spectrophotometric method, and level of 8-OHdG was estimated using a competitive sandwich ELISA assay. Our results showed a significant increase in the level of lipid peroxidation in group IV when compared to the control, group II and group III (p < 0.001). The activity of SOD was also significantly higher in group IV when compared to the control group (p < 0.001), group II (p < 0.001), and group III (p < 0.001). The level of GSH was also significantly lower in group IV when compared to the control group (p < 0.01), group II (p < 0.01), and group III (p < 0.01). The level of 8-OHdG was significantly higher in group IV than in the other groups (p < 0.01). The results suggest that oxidative stress is involved in the pathogenesis of cervical cancer, which is demonstrated by an increased level of lipid peroxidation and higher levels of 8-OHdG and an altered antioxidant defense system. © 2020
The see-saw of Keap1-Nrf2 pathway in cancer
(Elsevier Ireland Ltd, 2017) Poorti Pandey; Alok Kumar Singh; Mritunjai Singh; Mallika Tewari; Hari Shankar Shukla; Indrajeet Singh Gambhir
Keap1-Nrf2 pathway is continuously involved in the cytoprotection from oxidative stress generated due to various factors either extrinsic or intrinsic in origin. This role of Nrf2 in the response to oxidative stress is well established. Following oxidative insult, Nrf2 mediates the regulation of the inducible expression of cytoprotective genes. The level and functional capacity of Nrf2 is regulated at the post-transcriptional level, mainly through its association with an actin-associated protein, Keap1. Various studies reported that any discrepancy from their routine may lead to promotion of tumor as well. So there is need to explore their role in cytoprotection and tumor promotion if any. This review is an attempt to critically analyze the available data that may lighten up the present knowledge and unveil the new regime for cancer prevention and treatment. © 2017
Heavy metal pollution due to coal washery effluent and its decontamination using a macrofungus, Pleurotus ostreatus
(Academic Press, 2017) Huma Vaseem; V.K. Singh; M.P. Singh
Release of the effluent generated during washing of coal became a major problem for coal industries due to presence of many toxic metals and other pollutants. These effluents are the main source of pollution in rivers and other water bodies. Therefore in this study, we tried to analyse the toxicity of coal washery effluent (CWE) collected from one of the washery plant situated in Dhanbad, India. CWE was found to be very toxic containing large amount of suspended particles and many heavy metals above than their permissible limits. Mycoremediation of CWE was also performed to decontaminate heavy metals from the CWE using a macrofungi Pleurotus ostreatus. Efficiency of Pleurotus for remediation of heavy metals was found to be highest in the 50% diluted effluent (57.2% Mn, 82.6% Zn, 98.0% Ni, 99.9% Cu, 99.3% Co, 99.1% Cr, 89.2% Fe and 35.6% Pb) followed by 25% diluted effluent (33.0% Mn, 55.1% Zn, 97.8% Ni, 99.7% Cu, 97% Co, 84.4% Cr, 87.1% Fe and 73.4% Pb) and raw effluent (23.3% Mn, 73.1% Zn, 78.7% Ni, 87.5% Cu, 59.3% Co, 64.6% Cr, 34.6% Fe and 11.3% Pb) respectively. Increased activity of antioxidant enzymes, lipid peroxidation, concentration of metallothionein proteins and changes in peaks of FTIR spectra were also observed in fungal mycelia grown on the CWE containing media due to accumulation of different metals. Overall this study suggests that Pleurotus can be used as promising option for removal of heavy metals from the effluent released from washery plants and dilution of effluent could increase the efficiency of remediation. © 2017 Elsevier Inc.
Level of hydrogen peroxide affects expression and sub-cellular localization of Pax6
(Springer Netherlands, 2018) Sachin Shukla; Rajnikant Mishra
The Pax6 is a multifunctional pairedbox and homeobox containing transcription factor which is involved in several functions of brain, eyes, and pancreas. It regulates expression of genes involved in cell proliferation, differentiation, inflammation, oxidative stress management, and neuropathy. Dynamic changes in the sub-cellular localization of Pax6 are proposed to regulate its activity, however, the underlying mechanism remains poorly understood. The oxidative stress mediated changes were studied in sub-cellular localization of Pax6 in cultured cells derived from the eye (cornea) and pancreas. The impact of induced oxidative stress was investigated on reactive oxygen species scavenger molecules, Superoxide dismutase1 (SOD1) and Catalase, and a critical cell signalling molecule Transforming growth factor-beta (TGF-β1). The cells were treated with three different concentrations of H 2 O 2, viz., 0.3, 1.5, and 3.0 mM. The cell viability was analysed through Trypan blue dye exclusion assay. The localization of Pax6 was observed by immunofluorescence labeling, and alterations in levels of Pax6, SOD1, Catalase, and TGF-β1 were investigated by semi-quantitative RT-PCR. Nucleo-cytoplasmic shuttling of Pax6 was observed in cells of corneal epithelial (SIRC) and pancreatic origins (MIA-PaCa2). The percentage distribution of Pax6 in nuclear and cytoplasmic compartments of SIRC and MIA-PaCa2 cells was analyzed through ImageJ software. Level of hydrogen peroxide affects expression and sub-cellular localization of Pax6. Expression of Pax6 and TGF-β1 are directly associated with changes in sub-cellular localization of Pax6 and modulation in expression of Catalase. This may be the result of a cellular protective mechanism against peroxide-dependent cellular stress. © 2018, Springer Science+Business Media B.V., part of Springer Nature.
Reactive oxygen species and antioxidants: A continuous scuffle within the cell
(wiley, 2017) Supriya Tiwari
Reactive oxygen species (ROS) are highly reactive chemical entities, produced as a byproduct of many biochemical reactions occurring during the normal physiological functioning of plants. Various abiotic stresses lead to an overproduction of ROS which may be toxic and cause damage to proteins, lipids, DNA etc. ultimately resulting in oxidative stress. The plants posses a very efficient enzymatic and non-enzymatic antioxidant defense system which detoxifies the ROS and protects the cell from the ill-effects of oxidative stress. Imbalance between ROS generation and safe detoxification leads to accumulation of ROS resulting in a disruption of cellular homeostasis. Different cell organelles like mitochondria, chloroplasts, peroxisomes are important sites of ROS generation due to their oxidative type metabolism. These organelles have their own intrinsic antioxidant defense machinery which keeps a check on the ROS produced preventing its leakage into the cytosol. A constant duel continues between the ROS and the antioxidant defense system and the fate of the cell are decided upon by the outcome of interplay of antioxidants and ROS. The cell progresses on the normal metabolic path if the antioxidant defense system gets an upper hand in this duel. However, if ROS generation is enough to deplete the cellular antioxidants, the cell may proceed towards programmed cell death. The present chapter throws some light on this duel occurring in different sites of ROS generation in the cell. © 2018 John Wiley & Sons Ltd.

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