GR15 peptide of S-adenosylmethionine synthase (SAMe) from Arthrospira platensis demonstrated antioxidant mechanism against H2O2 induced oxidative stress in in-vitro MDCK cells and in-vivo zebrafish larvae model

Environmental Toxicology

Juliet

et al. 2022

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Parabens are synthetic antimicrobial compounds used as a preservative for extending the shelf life of food, pharmaceutical and cosmetic products. The alkyl chain length of the paraben esters positively correlates with their antimicrobial property. Hence, long-chain paraben esters, namely butylparaben and propylparaben, are used in combination as they have better solubility and antimicrobial efficacy. Extensive use of parabens has now resulted in the ubiquitous presence of these compounds in various human and environmental matrices. During early life, exposure to environmental contaminants is known to cause oxidative-stress mediated apoptosis in developing organs. The brain being one of the high oxygen-consuming, metabolically active and lipid-rich organ, it is primarily susceptible to reactive oxygen species (ROS) and lipid peroxidation (LP) induced neuronal cell death. The primary cause for the impairment in cognitive and emotional neurobehvioural outcomes in neurodegenerative disease was found to be associated with neuronal apoptosis. The present study aimed to study butylparaben and propylparaben's effect on zebrafish during early embryonic stages. Besides this, the association between alteration in anxiety-like neurobehavioral response with oxidative stress and antioxidant status in head region was also studied. The study results showed variation in the toxic signature left by butylparaben and propylparaben on developmental parameters such as hatching rate, survival and non-lethal malformations in a time-dependent manner. Data from the light-dark preference test showed embryonic exposure to butylparaben and propylparaben to trigger anxiety-like behavior in zebrafish larvae. In addition, a significant increase in intracellular ROS and LP levels correlated with suppressed antioxidant enzymes: superoxide dismutases (SOD), catalases (CAT), Glutathione peroxidase (GPx), glutathione S-transferase (GST), and Glutathione (GSH) activity in the head region of the zebrafish larvae. Acetylcholinesterase (AChE) activity was also suppressed in the exposed groups, along with increased nitric oxide production. The overall observations show increased oxidative stress indices correlating with upregulated expression of apoptotic cells in a dose-dependent manner. Collectively, our findings reveal butylparaben and propylparaben as an anxiogenic neuroactive Christy Lite, Ajay Guru, and Melita Juliet contributed equally to this study.

Section: Methodsmentioning

confidence: 99%

Section: Quantification Of Ros Level and Image Analysis In Zebrafish ...mentioning

confidence: 99%

Embryonic exposure to butylparaben and propylparaben induced developmental toxicity and triggered anxiety‐like neurobehavioral response associated with oxidative stress and apoptosis in the head of zebrafish larvae

Lite

Environmental Toxicology

Juliet

et al. 2022

Self Cite

“…The ABTS radical cation decolorization test [18] was used to assess the free radical scavenging activity of the compounds (NF1 and NF2). The reaction between 7 mM ABTS (SRL Pvt.…”

Section: Methodsmentioning

confidence: 99%

“…In all the above experiments, NF2 indicated better results at concentration 150 μM. Hence, 150 μM of NF2 is taken for gene expression analysis [18] . Antioxidant and anti‐inflammatory gene expression was examined to assess the effect of NF2 on LPS‐induced oxidative stress and to investigate the fundamental mechanism of action.…”

Section: Methodsmentioning

confidence: 99%

“…Hence, 150 μM of NF2 is taken for gene expression analysis. [18] Antioxidant and anti-inflammatory gene expression was examined to assess the effect of NF2 on LPS-induced oxidative stress and to investigate the fundamental mechanism of action. Total RNA extracted from zebrafish larvae (n = 30) after treatment and quantified using a Nano-Drop 2000c spectrophotometer (Thermo Fisher Scien-tific, USA).…”

Section: Antioxidant and Anti-inflammatory Gene Expressionmentioning

confidence: 99%

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Deacetylepoxyazadiradione Derived from Epoxyazadiradione of Neem (Azadirachta indica A. Juss) Fruits Mitigates LPS‐Induced Oxidative Stress and Inflammation in Zebrafish Larvae

Murugan

Rajesh

Chemistry & Biodiversity

et al. 2022

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Reactive oxygen species (ROS) produced by cell metabolism have a duplex role in oxidation and inflammation reactions which involve cell damage or repair responses. Excess ROS production has detrimental effects on the survival of cells. We examined the protective effect of a semi-natural compound NF2 (deacetylepoxyazadiradione), for its protective activity against free radical-mediated stress and inflammatory response to lipopolysaccharide (LPS) using zebrafish larvae. Preliminary antioxidant assays indicated an increase in scavenging of free radicals from NF2 than NF1 (Epoxyazadiradione) in a concentration-dependent manner. Cell cytotoxicity was determined using rat myoblast cell lines (L6), and more than 95 % of cell viability was obtained. Zebrafish developmental toxicity test indicated that NF2 is not toxic even at 150 μM. The percentage of ROS, lipid peroxidation, nitric oxide and apoptosis were reduced significantly in NF2 treated LPS-stressed zebrafish larvae. The reduced number of employed macrophages on NF2 treatment was observed in neutral red dyemarked macrophage localization images. Relative expression of antioxidant genes in zebrafish larvae after treatment with NF2 is significantly increased. The RT-PCR quantification of antioxidant and anti-inflammatory gene expression indicated decreased relative folds of pro-inflammatory cytokines, iNOS and increased relative folds of mitochondrial antioxidant genes (GR, GST and GPx) in LPS stressed zebrafish larvae after treatment with NF2. From the overall obtained results, it can be concluded that NF2 reduced the oxidative stress and inflammatory response by scavenging free radicals caused by LPS.

6‐Gingerdione Reduces Apoptotic Conditions in HepG2 Cells and Inhibits Inflammatory Cytokine Gene Expression in Alcoholic Liver Injured Zebrafish Larvae

Chemistry & Biodiversity

Manjunathan

Sudhakaran

et al. 2022

Self Cite

Antioxidant natural products and their analogs especially phenolic compounds, exhibit diverse biological properties, including anti‐inflammatory, antioxidant, and anticancer activities. Ginger which is widely used worldwide for various beneficial effects also contains several phenolic antioxidants, and 6‐gingerol is one of the natural products studied extensively. However, the molecular mechanism of synthetically synthesized 6‐gingerdione (compound 1) from 6‐gingerol was not known. In this study, compound 1 and methylated 6‐gingerdione (compound 2) were obtained semi synthetically from 6‐gingerol. Compound 1 and 2 are subjected to SwissADME prediction. Then the protective effect of compound 1 was analyzed in 2 % EtOH induced HepG2 cells and zebrafish larvae. Hydroxyl and nitric oxide scavenging assays reveal that compound 1 showed more antioxidant activity than compound 2 at 50 μM. Moreover, compound 1 exhibited good anti‐inflammatory activity via lipoxygenase inhibition and proteinase inhibition. Apoptosis and oxidative stress in HepG2 cells were induced by 2 % EtOH and treated with compound 1. Compound 1 significantly inhibited the EtOH induced nitric oxide production, apoptosis, and ROS generation in HepG2 cells. Encouraged by the in‐vitro antioxidant and anti‐inflammatory activities, compound 1 was then investigated for its protective effect in 2 % EtOH induced ALD zebrafish larva. Compound 1 protected the zebrafish larvae from liver injury by suppressing inflammatory (COX‐2, TNF‐α, and IL‐1β) and lipogenic genes (C/EBP‐α, SREBP1, and IL‐1β) while upregulating the antioxidant gene. Our findings indicate that compound 1 synthesized from 6‐gingerol ameliorated liver injury that likely, contributes to its potential antioxidant and anti‐inflammatory properties.