scholarly journals Toxic Effect of Platinum Compounds: Molecular Mechanisms of Toxicity

2021 ◽  
Vol 1 ◽  
pp. 81-88
Author(s):  
Mayyadah Mahmood Ali ◽  
Tavga Ahmed Aziz
Keyword(s):  
Side Effects ◽  
Molecular Mechanisms ◽  
Nuclear Dna ◽  
Hair Follicles ◽  
Toxic Effects ◽  
Platinum Compounds ◽  
Mechanisms Of Toxicity ◽  
Fast Growing ◽  
Chemotherapy Drugs ◽  
Platinum Based Chemotherapy

Despite their effectiveness as a crucial component of combination chemotherapy regimens against solid tumors, platinum compounds have many serious side effects that limit their use. This review article focuses on the various toxic effects of platinum compounds in cancer patients and the mechanisms of toxicity associated with each of these toxic effects. It also describes the future directions for developing novel platinum compounds, using both animal and human studies. The reference lists of relevant publications were included after searching the Google and Google Scholar databases, PubMed, and scientific journals. It focuses primarily on trials that were published between 2005 and 2020. Platinum-based medicines, as a soft nucleophile, can freely bind to peptides and proteins containing sulfur residues from thiol-containing amino acids like cysteine and methionine, as well as the antioxidant peptide glutathione. Platinum medicines, on the other hand, are primarily directed at nuclear DNA. Platinum medicines bind to normal cells as well as malignant cells, particularly those in fast growing tissues, causing a variety of dangerous side effects. Fast-growing tissues such as the mucous membranes of the mouth, throat, stomach, and intestines, bone marrow, and hair follicles can be damaged by cytotoxic chemotherapy drugs, resulting in gastrointestinal toxicities, myelosuppression, and hair loss. Platinum compounds also cause nephrotoxicity and hepatotoxicity, which are well-known side effects. Current platinum-based chemotherapy treatments have been restricted in the last decade, prompting a search for novel platinum-based medications with mechanisms of action distinct from those of existing chemotherapeutics.      

The side effects of platinum-based chemotherapy drugs: a review for chemists

2018 ◽  
Vol 47 (19) ◽  
pp. 6645-6653 ◽  
Author(s):  
Rabbab Oun ◽  
Yvonne E. Moussa ◽  
Nial J. Wheate
Keyword(s):  
Side Effects ◽  
Chemotherapy Drugs ◽  
Platinum Based Chemotherapy ◽  
Different Types ◽  
Platinum Chemotherapy

The platinum chemotherapy drugs cisplatin, carboplatin, and oxaliplatin are known to cause seven different types of side effects in patients.

scholarly journals Correction: The side effects of platinum-based chemotherapy drugs: a review for chemists

2018 ◽  
Vol 47 (23) ◽  
pp. 7848-7848 ◽  
Author(s):  
Rabbab Oun ◽  
Yvonne E. Moussa ◽  
Nial J. Wheate
Keyword(s):  
Side Effects ◽  
Dalton Trans ◽  
Chemotherapy Drugs ◽  
Platinum Based Chemotherapy

Correction for ‘The side effects of platinum-based chemotherapy drugs: a review for chemists’ by Rabbab Oun et al., Dalton Trans., 2018, 47, 6645–6653.

Ginger and Heart Health: From Mechanisms to Therapeutics

2020 ◽  
Vol 13 ◽  
Author(s):  
Sajad Fakhri ◽  
Jayanta Kumar Patra ◽  
Swagat Kumar Das ◽  
Gitishree Das ◽  
Mohammad Bagher Majnooni ◽  
...  
Keyword(s):  
Side Effects ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Health Benefits ◽  
Herbal Medicines ◽  
Cardiovascular Complications ◽  
National Database ◽  
Heart Health ◽  
Natural Entities ◽  
Cardioprotective Effects

Background: As a major cause of morbidity and mortality, cardiovascular diseases (CVDs) are globally increasing. In spite of recent development in the management of cardiovascular complications, CVDs have remained a medical challenge. Numerous conventional drugs are used to play cardioprotective roles; however, they are associated with several side effects. Considering the rich phytochemistry and fewer side effects of herbal medicines, they have gained particular attention to develop novel herbal drugs with cardioprotective potentials. Amongst natural entities, ginger is an extensively used and well-known functional food and condiment, possessing plentiful bioactivities, like antiinflammatory, antioxidant, and antimicrobial properties in several disorders management. Objective: The current review deliberated phytochemical properties as well as the ginger/ginger constituents' biological activities and health benefits in several diseases, with particular attention to cardiovascular complications. Methods: A comprehensive research was conducted using multiple databases, including Scopus, PubMed, Medline, Web of Science, national database (Irandoc and SID), and related articles in terms of the health benefits and cardioprotective effects of ginger/ginger constituents. These data were collected from inception until August 2019. Results: In recent years, several herbal medicines were used to develop new drugs with more potency and also minor side effects. Amongst natural entities, ginger is an extensively used traditional medicine in several diseases. The crude extract, along with related pungent active constituents, is mostly attributed to heart health. The cardioprotective effects of ginger are contributed to its cardiotonic, antihypertensive, anti-hyperlipidemia, and anti-platelet effects. The signaling pathways and molecular mechanisms of ginger regarding its cardioprotective effects are also clarified. Conclusion: This study revealed the biological activities, health benefits, and cardioprotective properties of ginger/ginger constituents along with related mechanisms of action, which gave new insights to show new avenue in the treatment of CVDs.

Toxicology

2017 ◽  
Author(s):  
Robert Laumbach ◽  
Michael Gochfeld
Keyword(s):  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Toxicity Testing ◽  
The Body ◽  
Toxic Substances ◽  
Basic Principles ◽  
Practical Applications ◽  
Mechanisms Of Toxicity ◽  
Body Distribution ◽  
Threshold Doses

This chapter describes the basic principles of toxicology and their application to occupational and environmental health. Topics covered include pathways that toxic substances may take from sources in the environment to molecular targets in the cells of the body where toxic effects occur. These pathways include routes of exposure, absorption into the body, distribution to organs and tissues, metabolism, storage, and excretion. The various types of toxicological endpoints are discussed, along with the concepts of dose-response relationships, threshold doses, and the basis of interindividual differences and interspecies differences in response to exposure to toxic substances. The diversity of cellular and molecular mechanisms of toxicity, including enzyme induction and inhibition, oxidative stress, mutagenesis, carcinogenesis, and teratogenesis, are discussed and the chapter concludes with examples of practical applications in clinical evaluation and in toxicity testing.

scholarly journals An audit of UK audiological practice in specialist paediatric oncology centres regarding hearing assessment of children at risk of ototoxicity due to chemotherapy

2021 ◽  
Vol 135 (1) ◽  
pp. 14-20
Author(s):  
E C M Brown ◽  
C Caimino ◽  
C L Benton ◽  
D M Baguley
Keyword(s):  
High Frequency ◽  
Good Practice ◽  
Paediatric Oncology ◽  
Chemotherapy Drugs ◽  
Team Working ◽  
Platinum Based Chemotherapy ◽  
Hearing Assessment ◽  
Self Test ◽  
The Uk ◽  
Monitoring Service

AbstractObjectivePlatinum-based chemotherapy drugs are associated with substantial ototoxicity. The hearing of children treated with these drugs should be closely monitored.MethodA questionnaire was sent out to the 19 audiology departments associated with national paediatric cancer specialist centres in the UK looking at current practice in ototoxicity monitoring.ResultsResponses were received from 17 of 19 centres (89 per cent). All offered some form of audiometric monitoring service. Extended high-frequency testing (9–20 kHz) was only utilised by 7 services (29 per cent). A majority of respondents were reluctant to consider self-test devices in paediatric ototoxicity monitoring (n = 9; 53 per cent). Provision of long-term audiological follow up is sporadic with only 4 (23 per cent) respondents keeping all children with normal hearing under review once treatment is completed.ConclusionWhile some good practice in paediatric ototoxicity was identified, opportunities exist to improve clinical practice and protocols, promote multidisciplinary team working and to utilise technologies such as extended high frequency and self-test audiometry.

scholarly journals A Preclinical Evaluation of the Antitumor Activities of Edible and Medicinal Mushrooms: A Molecular Insight

2017 ◽  
Vol 17 (2) ◽  
pp. 200-209 ◽  
Author(s):  
Thomson Patrick Joseph ◽  
Warren Chanda ◽  
Arshad Ahmed Padhiar ◽  
Samana Batool ◽  
Shao LiQun ◽  
...  
Keyword(s):  
Side Effects ◽  
Biological Activities ◽  
Genetic Alterations ◽  
In Vivo Models ◽  
Medicinal Mushrooms ◽  
Chemotherapy Drugs ◽  
Development Of Resistance ◽  
Preclinical And Clinical Studies

Cancer is the leading cause of morbidity and mortality around the globe. For certain types of cancer, chemotherapy drugs have been extensively used for treatment. However, severe side effects and the development of resistance are the drawbacks of these agents. Therefore, development of new agents with no or minimal side effects is of utmost importance. In this regard, natural compounds are well recognized as drugs in several human ailments, including cancer. One class of fungi, “mushrooms,” contains numerous compounds that exhibit interesting biological activities, including antitumor activity. Many researchers, including our own group, are focusing on the anticancer potential of different mushrooms and the underlying molecular mechanism behind their action. The aim of this review is to discuss PI3K/AKT, Wnt-CTNNB1, and NF-κB signaling pathways, the occurrence of genetic alterations in them, the association of these aberrations with different human cancers and how different nodes of these pathways are targeted by various substances of mushroom origin. We have given evidence to propose the therapeutic attributes and possible mode of molecular actions of various mushroom-originated compounds. However, anticancer effects were typically demonstrated in in vitro and in vivo models and very limited number of studies have been conducted in the human population. It is our belief that this review will help the research community in designing concrete preclinical and clinical studies to test the anticancer potential of mushroom-originated compounds on different cancers harboring particular genetic alteration(s).

scholarly journals Acquired Glucocorticoid Resistance Due to Homologous Glucocorticoid Receptor Downregulation: A Modern Look at an Age-Old Problem

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2529
Author(s):  
Lee-Maine L. Spies ◽  
Nicolette J. D. Verhoog ◽  
Ann Louw
Keyword(s):  
Transcription Factor ◽  
Side Effects ◽  
Pharmaceutical Industry ◽  
Glucocorticoid Receptor ◽  
Steroid Hormones ◽  
Molecular Mechanisms ◽  
Protein Levels ◽  
Current Review ◽  
Role Players ◽  
Receptor Conformation

For over 70 years, the unique anti-inflammatory properties of glucocorticoids (GCs), which mediate their effects via the ligand-activated transcription factor, the glucocorticoid receptor alpha (GRα), have allowed for the use of these steroid hormones in the treatment of various autoimmune and inflammatory-linked diseases. However, aside from the onset of severe side-effects, chronic GC therapy often leads to the ligand-mediated downregulation of the GRα which, in turn, leads to a decrease in GC sensitivity, and effectively, the development of acquired GC resistance. Although the ligand-mediated downregulation of GRα is well documented, the precise factors which influence this process are not well understood and, thus, the development of an acquired GC resistance presents an ever-increasing challenge to the pharmaceutical industry. Recently, however, studies have correlated the dimerization status of the GRα with its ligand-mediated downregulation. Therefore, the current review will be discussing the major role-players in the homologous downregulation of the GRα pool, with a specific focus on previously reported GC-mediated reductions in GRα mRNA and protein levels, the molecular mechanisms through which the GRα functional pool is maintained and the possible impact of receptor conformation on GC-mediated GRα downregulation.

scholarly journals Methotrexate Toxicity: Molecular Mechanisms and Management

2021 ◽  
pp. 204-217
Author(s):  
Riyadh S. Almalki ◽  
Hala Eweis ◽  
Fatemah Kamal ◽  
Dina Kutbi
Keyword(s):  
Side Effects ◽  
Cancer Chemotherapy ◽  
Pulmonary Toxicity ◽  
Molecular Mechanisms ◽  
Hematological Toxicity ◽  
Comprehensive Understanding ◽  
First Line ◽  
Cutaneous Toxicity ◽  
Gi Toxicity ◽  
Line Drug

Methotrexate (MTX) is the most widely used drug in cancer chemotherapy and is considered to be the first-line drug for the treatment of a number of rheumatic and non-rheumatic disorders. The pulmonary toxicity, hepatotoxicity of MTX are two of its major side effects. Other toxicities such as endocrinological toxicity, GI toxicity, cutaneous toxicity, hematological toxicity, fatal malfunction or loss, and malignancy can also occur, but at a significantly lower rate of prevalence. This review aims to provide a comprehensive understanding of the molecular mechanisms of methotrexate toxic effects and Lastly, we discussed the management of this toxicity.

scholarly journals Mitochondrial Respiratory Chain Protein Co-Regulation in the Human Brain

2021 ◽  
Author(s):  
Caroline Trumpff ◽  
Edward Owusu-Ansah ◽  
Hans-Ulrich Klein ◽  
Annie Lee ◽  
Vladislav Petyuk ◽  
...  
Keyword(s):  
Human Brain ◽  
Respiratory Chain ◽  
Complex I ◽  
Molecular Mechanisms ◽  
Nuclear Dna ◽  
Mitochondrial Protein ◽  
Mitochondrial Respiratory Chain ◽  
Mtdna Copy Number ◽  
Mt Dna ◽  
Mitochondrial Respiratory

Mitochondrial respiratory chain (RC) function requires the stochiometric interaction among dozens of proteins but their co-regulation has not been defined in the human brain. Here, using quantitative proteomics across three independent cohorts we systematically characterized the co-regulation patterns of mitochondrial RC proteins in the human dorsolateral prefrontal cortex (DLPFC). Whereas the abundance of RC protein subunits that physically assemble into stable complexes were correlated, indicating their co-regulation, RC assembly factors exhibited modest co-regulation. Within complex I, nuclear DNA-encoded subunits exhibited >2.5-times higher co-regulation than mitochondrial (mt)DNA-encoded subunits. Moreover, mtDNA copy number was unrelated to mtDNA-encoded subunits abundance, suggesting that mtDNA content is not limiting. Alzheimer disease (AD) brains exhibited reduced abundance of complex I RC subunits, an effect largely driven by a 2-4% overall lower mitochondrial protein content. These findings provide foundational knowledge to identify molecular mechanisms contributing to age- and disease-related erosion of mitochondrial function in the human brain.

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