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Human Toxicology and Metabolic Disease with Exposure to Drugs

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A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Drugs Toxicity".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 6577

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Special Issue Editors

Prof. Dr. Surajit Pathak

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Guest Editor

Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Kelambakkam, Chennai 603103, Tamil Nadu, India
Interests: colorectal cancer; miRNA; regenerative medicine; aging; molecular biology

Dr. Antara Banerjee

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Guest Editor

Faculty of Allied Health Sciences, Chettinad Academy of Research and Education, Kelambakkam, Chennai 603103, Tamil Nadu, India
Interests: regenerative medicine; stem cell therapeutics; colorectal cancer; tumor miRNA environment; epigenetics

Special Issue Information

Dear Colleagues,

During the past two decades of research in chemical toxicology, the investigation of drug response and the relationship between drug metabolism and drug-mediated toxicity has witnessed significant progress in a variety of fields. Toxicology is the study of the adverse effects of chemical, physical, or biological agents on living organisms and the ecosystem, including the prevention and amelioration of the largest adverse effects. The combination of toxins results in metabolic disease. Our understanding of the science underlying metabolic disease is evolving in this fast-moving field. Metabolic disease is responsible for a number of specific abnormalities in an individual. These abnormalities include type-2 diabetes, obesity, high blood pressure, increased risk of cardiovascular disease (CVD), dyslipidemia, hyperglycemia, endothelial dysfunction, and platelet hyperactivity. The complicated treatment strategies that include a wide variety of medications may result in adverse drug interactions and poor patient adherence, both of which contribute to ineffective disease management. In order to understand the causes of metabolic diseases in humans, scientists from a broad range of disciplines must identify the presence of toxic pharmacological ingredients in the body, assess their toxicity, and evaluate the probability of their exposure. Numerous drug-mediated hazardous and potentially harmful chemical components and their compounds have been the subject of extensive study for quite some time. This study, together with technological development, has enabled the dissemination of a plethora of data relating to the topic at hand. The current body of knowledge, despite its extensive nature, is still insufficient to explain the etiology of certain metabolic diseases. This is because it is not a simple task to observe the changing chemical elements content, distribution, absorption, and interrelations between the vital toxic elements in the human body. Moreover, factors including diet, stress, lifestyle, and genetic predisposition may all interfere with the body’s ability to maintain homeostasis and prevent disease.

This Special Issue aims to present research papers as well as critical reviews that address issues focusing on understanding the role that drug-mediated toxicity and potentially toxic chemical components play in the development of metabolic diseases. It is envisaged that this would shed more light on the numerous functions that toxicological components have in humans and could support the development of therapeutic strategies, ultimately helping us to better understand the human body’s sensitivity to metabolic diseases.

Prof. Dr. Surajit Pathak
Dr. Antara Banerjee
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

toxicology
metabolic diseases
drug toxicity
drug metabolism
chemical toxicity
therapeutic approaches

Published Papers (3 papers)

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Research

17 pages, 21218 KiB

Open AccessArticle

Inducing Cytotoxicity in Colon Cancer Cells and Suppressing Cancer Stem Cells by Dolasetron and Ketoprofen through Inhibition of RNA Binding Protein PUM1

by Ravi Gor, Ali Gharib, Priya Dharshini Balaji, Thirumurthy Madhavan and Satish Ramalingam

Toxics 2023, 11(8), 669; https://doi.org/10.3390/toxics11080669 - 03 Aug 2023

Cited by 1 | Viewed by 1968

Abstract

Clinical trials of new drugs often face a high failure rate of approximately 45 percent due to safety and toxicity concerns. Repurposing drugs with well-established safety profiles becomes crucial in addressing this challenge. Colon cancer ranks as the third most prevalent cancer and the second leading cause of cancer related mortality worldwide. This study focuses on the RNA-binding protein pumilio1 (PUM1), a member of the PUF family involved in post-transcriptional gene expression regulation. By utilizing molecular docking techniques and FDA-approved drugs, potential inhibitors against PUM1 were identified. Notably, dolasetron and ketoprofen demonstrated promising results, exhibiting strong binding affinity, hydrophobic interactions, and favorable chemical reactivity according to Conceptual-DFT calculations. Both compounds effectively reduced cell viability, with IC50 values of 150 µM and 175 µM, respectively and shows long term inhibitory effects as seen by reduced in number of colonies. Moreover, they exhibited inhibitory effects on colon cancer stem cells, as indicated by reduced colonospheroid size and numbers. Apoptosis is induced by these compounds and has triggered activation of executioner caspase 3/7 in HCT116 cells which is evident through a caspase 3/7 assay and AO/EB staining, while the non-toxic effect of these compounds was evident from viability against non-cancerous cell line and hemolysis assay. Additionally, the treatment group showed a significant decrease in PUM1 and cancer stem cell markers expression compared to the control group. In conclusion, this study highlights the potential of targeting PUM1 as a novel approach to colon cancer treatment. Dolasetron and ketoprofen demonstrate promise as effective anti-cancer and anti-cancer stem cell drugs, inducing apoptosis in colon cancer cells through inhibition of PUM1. Full article

(This article belongs to the Special Issue Human Toxicology and Metabolic Disease with Exposure to Drugs)

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8 pages, 575 KiB

Open AccessArticle

Use of Antibiotics in Poisonous Ingestions of Corrosives and Organophosphates: A Retrospective Cohort Study

by Joud K. Altuwaijri, Fatma M. Hamiduddin, Raghad H. Khafaji, Leyan T. Almaghrabi, Hussain T. Bakhsh and Abrar K. Thabit

Toxics 2023, 11(4), 300; https://doi.org/10.3390/toxics11040300 - 24 Mar 2023

Cited by 1 | Viewed by 1528

Abstract

The use of antibiotics following oral poisoning by corrosives and organophosphates is controversial. We assessed the clinical outcomes of using antibiotics in acute poisonous ingestion involving corrosives or organophosphates by conducting a retrospective cohort study of patients presenting to the emergency department following ingestion of corrosives or organophosphates who received either antibiotics or supportive care. The endpoints included clinical stability, length of stay (LOS), and mortality. Of 95 patients, 40 received antibiotics and 55 received supportive care. The median age was 2.1 and 2.7 years, respectively (p = 0.053). Bacterial growth was shown in only 2 of 28 cultures (both were respiratory), but with hospital-acquired organisms as it was shown ≥4 days post-admission. Clinical stability rates were 60% and 89.1% in the antibiotic and supportive care groups, respectively (p < 0.001). Median LOS was 3 vs. 0 days (p < 0.001), and no mortality was recorded. NG/G-tube placement was the only factor associated with clinical failure (OR, 20.97; 95% CI, 2.36–186.13). Antibiotic use was not associated with higher chances of clinical stability, which may suggest that their use was unnecessary. Clinicians are encouraged to use antibiotics wisely, and only in the presence of a clear indication of an infection. This study provides a basis for future prospective studies to confirm its findings. Full article

(This article belongs to the Special Issue Human Toxicology and Metabolic Disease with Exposure to Drugs)

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24 pages, 6443 KiB

Open AccessArticle

Hypoglycemic Potential of Carica papaya in Liver Is Mediated through IRS-2/PI3K/SREBP-1c/GLUT2 Signaling in High-Fat-Diet-Induced Type-2 Diabetic Male Rats

by Jeane Rebecca Roy, Coimbatore Sadagopan Janaki, Selvaraj Jayaraman, Vishnu Priya Veeraraghavan, Vijayalakshmi Periyasamy, Thotakura Balaji, Madhavan Vijayamalathi, Ponnusamy Bhuvaneswari and Panneerselvam Swetha

Toxics 2023, 11(3), 240; https://doi.org/10.3390/toxics11030240 - 01 Mar 2023

Cited by 3 | Viewed by 2252

Abstract

Regardless of socioeconomic or demographic background, the prevalence of type 2 diabetes mellitus, which affects more than half a billion people worldwide, has been steadily increasing over time. The health, emotional, sociological, and economic well-being of people would suffer if this number is not successfully handled. The liver is one of the key organs accountable for sustaining metabolic balance. Elevated levels of reactive oxygen species inhibit the recruitment and activation of IRS-1, IRS-2, and PI3K-Akt downstream signaling cascade. These signaling mechanisms reduce hepatic glucose absorption and glycogenesis while increasing hepatic glucose output and glycogenolysis. In our work, an analysis of the molecular mechanism of Carica papaya in mitigating hepatic insulin resistance in vivo and in silico was carried out. The gluconeogenic enzymes, glycolytic enzymes, hepatic glycogen tissue concentration, oxidative stress markers, enzymatic antioxidants, protein expression of IRS-2, PI3K, SREBP-1C, and GLUT-2 were evaluated in the liver tissues of high-fat-diet streptozotocin-induced type 2 diabetic rats using q-RT-PCR as well as immunohistochemistry and histopathology. Upon treatment, C. papaya restored the protein and gene expression in the liver. In the docking analysis, quercetin, kaempferol, caffeic acid, and p-coumaric acid present in the extract were found to have high binding affinities against IRS-2, PI3K, SREBP-1c, and GLUT-2, which may have contributed much to the antidiabetic property of C. papaya. Thus, C. papaya was capable of restoring the altered levels in the hepatic tissues of T2DM rats, reversing hepatic insulin resistance. Full article

(This article belongs to the Special Issue Human Toxicology and Metabolic Disease with Exposure to Drugs)

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