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Fulltext Toxicity assessment of gallic acid loaded graphene oxide (GAGO) nano-formulation in zebrafish (Danio Rerio) embryos

Ahmad Ashraful Hadi Abdul Ghafor, Nurhuda Elias, Suhaili Shams, Faizah Md Yasin, Sarchio, Seri Narti Edayu

Pertanika Journal of Science & Technology, 2020;28(1):311-326.
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Gallic acid (GA) is a phenolic compound found in almost all plants and has been reported to possess powerful health benefits such as anti-oxidant, anti-inflammatory, anti-cancer, and anti-diabetic properties. However, GA suffers a short half-life when administered in vivo. Recent studies have employed graphene oxide (GO), a biocompatible and cost-effective graphene derivative, as a nanocarrier for GA. However, the toxicity effect of this formulated nano-compound has not been fully studied. Thus, the present study aims to evaluate the toxicity and teratogenicity of GA loaded GO (GAGO) against zebrafish embryogenesis to further advance the development of GA as a therapeutic agent. GAGO was exposed to zebrafish embryos (n ≥ 10; 24hr post fertilization (hpf)) at different concentrations (0-500 μg/ml). The development of zebrafish was observed and recorded twice daily for four days. The toxicity of pure GO and GA was also observed at similar concentrations. Distilled water was used as control throughout the experiment. A significantly high mortality rate, delayed hatching rate and low heartbeat were recorded in embryos exposed to GO at concentrations of ≥ 150 μg/ml at 48 hr (p
Fulltext Synthesis, Characterization, and Toxicity Assessment of Pluronic F127-Functionalized Graphene Oxide on the Embryonic Development of Zebrafish (Danio rerio)

Shamsi S, Alagan AA, Sarchio SNE, Md Yasin F

Int J Nanomedicine, 2020;15:8311-8329.
PMID: 33149578 DOI: 10.2147/IJN.S271159

Background: In the current literature, there are ongoing debates on the toxicity of graphene oxide (GO) that demonstrate contradictory findings regarding its toxicity profile. As a potential drug carrier, these findings are very concerning due to the safety concerns in humans, as well as the dramatic rise of GO being excreted into the environment. Therefore, there is an imperative need to mitigate the potential toxicity of GO to allow for a safer application in the future.
Purpose: The present study aims to address this issue by functionalizing GO with Pluronic F127 (PF) as a means to mitigate toxicity and resolve the biocompatibility of GO. Although results from previous studies generally indicated that Pluronic functionalized GO exhibits relatively low toxicity to living organisms, reports that emphasize on its toxicity, particularly during embryonic developmental stage, are still scarce.
Methods: In the present study, two different sizes of native GO samples, GO and NanoGO, as well as PF-functionalized GO, GO-PF and NanoGO-PF, were prepared and characterized using DLS, UV-Vis, Raman spectroscopy, FTIR, and FESEM analyses. Toxicological assessment of all GO samples (0-100 µg/mL) on zebrafish embryonic developmental stages (survival, hatching and heart rates, and morphological changes) was recorded daily for up to 96 hours post-fertilization (hpf).
Results: The toxicity effects of each GO sample were observed to be higher at increasing concentrations and upon prolonged exposure. NanoGO demonstrated lower toxicity effects compared to GO. GO-PF and NanoGO-PF were also found to have lower toxicity effects compared to native GO samples. GO-PF showed the lowest toxicity response on zebrafish embryo.
Conclusion: These findings highlight that toxicity is dependent on the concentration, size, and exposure period of GO. Functionalization of GO with PF through surface coating could potentially mitigate the toxicity effects of GO in embryonic developmental stages, but further investigation is warranted for broader future applications.
Fulltext Insomnia and depression levels among Malaysian undergraduate students in the Faculty of Medicine and Health Sciences (FMHS), Universiti Putra Malaysia (UPM) during Movement Control Order (MCO)

Iqbal RM, Binti Riza Effendi NI, Syed Alwi SS, Saidi HI, Sarchio SNE

PLoS One, 2023;18(10):e0283098.
PMID: 37816038 DOI: 10.1371/journal.pone.0283098

Rapid outbreak of coronavirus disease 2019 has caused the implementation of the movement control order (MCO) which aimed to reduce the spread in Covid-19 infections. While some may find it easy to adjust to the new norm, others found it difficult to switch from their normal routines and habits as according to the MCO SOP. This resulted in a more frequent insomnia and depression that subsequently impacted their mental health. Insomnia and depression levels are examined in this study as they relate to the Covid-19 Pandemic and the MCO among Malaysian undergraduate health sciences students at the Faculty of Medicine and Health Sciences, UPM. Random sampling methods were utilised with consideration of inclusion and exclusion criteria. The Patient Health Questionnaire-9 (PHQ-9) and the Insomnia Severity Index (ISI) were the instrument packages used in this investigation. An internet platform was used to distribute the questionnaire. Based on the results, it is concluded that depression and insomnia are significantly correlated, with a p-value of 0.05. This study also revealed the link between the severity of insomnia and the severity of depression among UPM students studying health sciences. The percentage of students with depression and insomnia was rather high (54.9% and 33.9%, respectively), and this occurred during the second wave of Covid-19 cases in Malaysia.
Fulltext Biocompatibility Study of Curcumin-Loaded Pluronic F127 Nanoformulation (NanoCUR) against the Embryonic Development of Zebrafish (Danio rerio)

Abdullah SNS, Subramaniam KA, Muhamad Zamani ZH, Sarchio SNE, Md Yasin F, Shamsi S

Molecules, 2022 Jul 14;27(14).
PMID: 35889367 DOI: 10.3390/molecules27144493

Curcumin (CUR) has been studied for its biomedical applications due to its active biological properties. However, CUR has limitations such as poor solubility, low bioavailability, and rapid degradation. Thus, CUR was nanoformulated with the application of polymeric micelle. Previous studies of CUR-loaded Pluronic F127 nanoformulation (NanoCUR) were generally prioritized toward cancer cells and its therapeutic values. There are reports that emphasize the toxicity of CUR, but reports on the toxicity of NanoCUR on embryonic developmental stages is still scarce. The present study aims to investigate the toxicity effects of NanoCUR on the embryonic development of zebrafish (Danio rerio). NanoCUR was synthesized via thin film hydration method and then characterized using DLS, UV-Vis, FTIR, FESEM, and XRD. The toxicity assessment of NanoCUR was conducted using zebrafish embryos, in comparison to native CUR, as well as Pluronic F127 (PF) as the controls, and ROS assay was further carried out. It was revealed that NanoCUR showed an improved toxicity profile compared to native CUR. NanoCUR displayed a delayed toxicity response and showed a concentration- and time-dependent toxicity response. NanoCUR was also observed to generate a significantly low reactive oxygen species (ROS) compared to native CUR in ROS assay. Overall, the results obtained highlight the potential of NanoCUR to be developed in clinical settings due to its improved toxicity profile compared to CUR.
Fulltext Stability, Toxicity, and Antibacterial Potential of Gallic Acid-Loaded Graphene Oxide (GAGO) Against Methicillin-Resistant Staphylococcus aureus (MRSA) Strains

Shamsi S, Abdul Ghafor AAH, Norjoshukrudin NH, Ng IMJ, Abdullah SNS, Sarchio SNE, et al.

Int J Nanomedicine, 2022;17:5781-5807.
PMID: 36474524 DOI: 10.2147/IJN.S369373

BACKGROUND: The impetuous usage of antibiotics has led to the perpetual rise of methicillin-resistant Staphylococcus aureus (MRSA), which has garnered the interest of potential drug alternatives, including nanomaterials.
PURPOSE: The present study investigates the stability, toxicity, and antibacterial potential of gallic acid-loaded graphene oxide (GAGO) on several MRSA strains.
METHODS: The stability of a synthesized and characterized GAGO was monitored in different physiological media. The toxicity profile of GAGO was evaluated in 3T3 murine fibroblast cells and the embryonic zebrafish model. The antibacterial activity of GAGO against MRSA, methicillin-susceptible S. aureus (MSSA), and community-acquired MRSA; with or without Panton-valentine leucocidin gene (MRSA-pvl+ and MRSA-pvl-) was investigated through disk diffusion, CFU counting method, time-kill experiment, and high-resolution transmission electron microscopy (HRTEM) observation.
RESULTS: A stable GAGO nanocomposite has shown an improved toxicity profile in 3T3 murine fibroblast cells and zebrafish embryos, besides exhibiting normal ROS levels than graphene oxide (GO) and GA (gallic acid). The nanocomposite inhibited the growth of all bacterial strains employed. The effectiveness of the GAGO nanocomposite was comparable to cefoxitin (CFX), at ≥150 µg/mL in MRSA and MSSA. GAGO exhibited a significantly delayed response towards MRSA-pvl+ and MRSA-pvl-, with increased inhibition following 8 to 24 h of exposure, while comparable activity to native GA was only achieved at 24 h. Meanwhile, for MRSA and MSSA, GAGO had a comparable activity with native GA and GO as early as 2 h of exposure. HRTEM observation further reveals that GAGO-exposed cells were membrane compromised.
CONCLUSION: In summary, the present study indicates the antibacterial potential of GAGO against MRSA strains, but further study is warranted to understand the mechanism of action of GAGO and its resistance in MRSA strains.