Preface

**Section 4 Cytotoxic Endpoints 115**

**VI** Contents

**Plant Models 117**

**Development 131**

**Nanocomposites 149**

**Analysis 177**

Kosel

**Nanorods: Part 1 209**

**Nanorods—Part 2 233**

Chapter 7 **Cyto(Geno)Toxic Endpoints Assessed via Cell Cycle Bioassays in**

Chapter 8 **Role of Cytotoxicity Experiments in Pharmaceutical**

**Section 5 Nanomaterials and Nanoparticles and Nanocrystals 147**

Chapter 9 **Biocompatibility of Doped Semiconductors Nanocrystals and**

Chapter 10 **Toxicity of Titanate Nanosheets on Human Immune Cells 163**

Chapter 11 **General Cytotoxicity and Its Application in Nanomaterial**

Chapter 12 **Review of In vitro Toxicity of Nanoparticles and**

Chapter 13 **Review of In Vitro Toxicity of Nanoparticles and**

Magdalena Jedrzejczak-Silicka and Ewa Mijowska

Larissa Fonseca Andrade Vieira and Graciele Lurdes Silveira

Ildikó Bácskay, Dániel Nemes, Ferenc Fenyvesi, Judit Váradi, Gábor Vasvári, Pálma Fehér, Miklós Vecsernyés and Zoltán Ujhelyi

Anielle Christine Almeida Silva, Mariana Alves Pereira Zóia, Lucas Ian Veloso Correia, Fernanda Van Petten Vasconcelos Azevedo, Aline Teodoro de Paula, Larissa Prado Maia, Layara Santana de Carvalho, Loyna Nobile Carvalho, Maria Paula Camargo Costa, Layssa Carrilho Giaretta, Renata Santos Rodrigues, Veridiana de Melo Ávila, Luiz Ricardo Goulart and Noelio Oliveira Dantas

Yasumitsu Nishimura, Daisuke Yoshioka, Naoko Kumagai-Takei, Suni Lee, Hidenori Matsuzaki, Kei Yoshitome and Takemi Otsuki

Jose Efrain Perez, Nouf Alsharif, Aldo Isaac Martínez Banderas, Basmah Othman, Jasmeen Merzaban, Timothy Ravasi and Jürgen

Jose E. Perez, Nouf Alsharif, Aldo I. Martínez-Banderas, Basmah Othman, Jasmeen Merzaban, Timothy Ravasi and Jürgen Kosel

The book "Cytotoxicity" is a web-based resource, encompassing some of the natural cyto‐ toxicity and different chemical substances, such as natural coumarins, colchicine alkaloids, titanate nanosheets, asbestos fiber, nanomaterials, nanocrystals and composites, and curcu‐ min-loaded copolymer encapsulated ZnO nanocomposites. This e-resource comprises four different parts:


The first chapter, by Dr. Takemi Otsuki et al. from Japan, describes the different perspec‐ tives of "cytotoxicity caused by asbestos fiber and acquisition of resistance by continuous exposure in human T cell." Considering the most important issue of asbestos-exposed popu‐ lation, such as malignancies, namely, mesothelioma and lung cancer after the long-term la‐ tent period, the mechanisms should be explored as well as be prevented. This issue is important for human health.

The second chapter "The Cytotoxic, Antimicrobial, and Anticancer Properties of Antimicro‐ bial Nisin Z Alone and in Combination with Conventional Treatments," by Dr. Johannes Wentzel et al. from North-West University, South Africa, highlights the cytotoxic, antimicro‐ bial, and anticancer properties of antimicrobial nisin Z alone and in combination with con‐ ventional treatments, and they discussed the anticancer potential of nisin Z toward cultured melanoma cells, hence advocating safety and caution regarding their indiscriminate use by the population.

The third chapter "Cytotoxic Colchicine Alkaloids: From Plants to Drug," by Dr. Joanna Kurek, Chemistry Department, Adam Mickiewicz University, Poznań, Poland, deals with the plants of Liliaceae family that contains colchicine; colchinoids; natural, semisynthetic, and synthetic colchicines; and C-10 sulfur-containing derivatives as a main alkaloid, which has cytotoxic activity and cytotoxic activity of colchicine and its derivatives. Furthermore, we have provided information on the pharmacological use of colchicine, drugs with colchi‐ cine derivatives, and docking studies.

The fourth chapter, by Abdelmajid Zyad et al. from Morocco, discusses some examples of carvacrol, thymol, carveol, carvone, eugenol, isopulegol, and artemisinin as well as polyphe‐ nol extracts that have been studied in their laboratory. It is clear that if we understand the

molecular mechanisms of the various interactions between these cytotoxic molecules on the one hand and the tumor cells in their tumoral environments on the other hand, we can devel‐ op new therapeutic modalities to overcome the side effects of these molecules and to fight.

Finally, Dr. Jurgen Kosel et al. from Kingdom of Saudi Arabia summarize "Cytotoxicity of Nanoparticles: Part 1 and Part 2." This chapter on toxicological effects of nanostructures fo‐ cuses mostly on the cytotoxicity of nanoparticles and their internalization, activated signal‐

The book *Cytotoxicity* is an essential reading to all medical students, biologists, biochemists, and professionals involved in the field of toxicology. This book is a useful and ideal guide for novice researchers interested in learning research methods to study cytotoxic bioactive

**Assoc. Prof. Dr. Tülay Aşkin Çelik**

Aydın, Turkey

Preface IX

Adnan Menderes University, Art and Science Faculty

ing pathways, and cellular response.

compounds.

The fifth chapter, by Dr. Omid Gholami from Iran, summarizes "Natural Coumarins and Cyto‐ toxicity, Apoptosis Induction and Mcl-1 Regulation in Chronic Lymphocytic Leukemia (CLL)." Coumarins are one of the important cytotoxic agents. They could induce apoptosis and regulate Mcl-1 expression in CLL cell lines. He says that in future, they hope that the coumarins can be used in the treatment of cancer and that detailed studies are needed in this regard.

The sixth chapter, by Dr. Larissa Fonseca Andrade Vieira and Dr. Graciele Lurdes Silveira from the Biology Department, Federal University of Lavras, Lavras, MG, Brazil, describes at cellular level the cytotoxicity, genotoxicity, and mutagenicity in the parameters determined by the cyto(geno)toxic endpoints as mitotic index, DNA fragmentation, induction of cell death, and malfunction of cellular structures leading to chromosome and cell cycle altera‐ tions. Each of these endpoints discussed presents details in this chapter.

The seventh chapter outlines a way of understanding "Role of Cytotoxicity Experiments in Pharmaceutical Development" by Dr. Ildikó Bácskay et al. from the Department of Pharma‐ ceutical Technology, Faculty of Pharmacy, University of Debrecen, Hungary, and discusses in detail some of the cytotoxicity experiments that are a crucial part of a modern pharma‐ ceutical development process in the chapter.

The recent increasing interest in the use of different nanoparticles in biological and medical applications encouraged scientists to analyze their potential impact on biological systems. *The application of different nanomaterials in biological environment is strongly limited due to the agglomeration problem.* The present overview describes and compares widely used biocom‐ patibility/cytotoxicity assays in nanomaterial studies. Due to the type of nanoparticles and their properties, applicability of popular assays used for screening of engineered nanomate‐ rials might be limited.

The eighth chapter "Biocompatibility of Doped Semiconductor Nanocrystals and Compo‐ sites," by Dr. Anielle Christine Almeida Silva et al. from Brazil, looks at doped semiconduc‐ tor nanocrystals and composites of their potential toxicity and uses. This chapter summarizes the characterization of doped nanocrystals and composites; Ca-doped ZnO, Agand Eu-doped ZnO, and Ni-doped ZnO NCs; their biocompatibility; and applications and uncovers how these nanocrystals present desirable biocompatible properties, which can be useful as antitumoral and antimicrobial inducing agents, which differ markedly from toxic properties observed in other general nanocrystals.

The ninth chapter outlines a way of understanding "Toxicity of Titanate Nanosheets on Hu‐ man Immune Cells," which deals with the salient aspects of the influence of titanate nano‐ sheets in promoting well-being and health for human. Dr. Yasumitsu Nishimura and colleagues from Japan discussed the critical TiNSs material, which has the harmful potential to cause caspase-dependent apoptosis of human immune cells to the same degree as asbestos.

The 10th chapter, by Dr. Magdalena Jedrzejczak-Silicka and Ewa Mijowska from the Labora‐ tory of Cytogenetics, West Pomeranian University of Technology, Poland, describes the "General Toxicity and Its Application in the Nanomaterials Analysis."

Finally, Dr. Jurgen Kosel et al. from Kingdom of Saudi Arabia summarize "Cytotoxicity of Nanoparticles: Part 1 and Part 2." This chapter on toxicological effects of nanostructures fo‐ cuses mostly on the cytotoxicity of nanoparticles and their internalization, activated signal‐ ing pathways, and cellular response.

molecular mechanisms of the various interactions between these cytotoxic molecules on the one hand and the tumor cells in their tumoral environments on the other hand, we can devel‐ op new therapeutic modalities to overcome the side effects of these molecules and to fight. The fifth chapter, by Dr. Omid Gholami from Iran, summarizes "Natural Coumarins and Cyto‐ toxicity, Apoptosis Induction and Mcl-1 Regulation in Chronic Lymphocytic Leukemia (CLL)." Coumarins are one of the important cytotoxic agents. They could induce apoptosis and regulate Mcl-1 expression in CLL cell lines. He says that in future, they hope that the coumarins can be used in the treatment of cancer and that detailed studies are needed in this regard.

The sixth chapter, by Dr. Larissa Fonseca Andrade Vieira and Dr. Graciele Lurdes Silveira from the Biology Department, Federal University of Lavras, Lavras, MG, Brazil, describes at cellular level the cytotoxicity, genotoxicity, and mutagenicity in the parameters determined by the cyto(geno)toxic endpoints as mitotic index, DNA fragmentation, induction of cell death, and malfunction of cellular structures leading to chromosome and cell cycle altera‐

The seventh chapter outlines a way of understanding "Role of Cytotoxicity Experiments in Pharmaceutical Development" by Dr. Ildikó Bácskay et al. from the Department of Pharma‐ ceutical Technology, Faculty of Pharmacy, University of Debrecen, Hungary, and discusses in detail some of the cytotoxicity experiments that are a crucial part of a modern pharma‐

The recent increasing interest in the use of different nanoparticles in biological and medical applications encouraged scientists to analyze their potential impact on biological systems. *The application of different nanomaterials in biological environment is strongly limited due to the agglomeration problem.* The present overview describes and compares widely used biocom‐ patibility/cytotoxicity assays in nanomaterial studies. Due to the type of nanoparticles and their properties, applicability of popular assays used for screening of engineered nanomate‐

The eighth chapter "Biocompatibility of Doped Semiconductor Nanocrystals and Compo‐ sites," by Dr. Anielle Christine Almeida Silva et al. from Brazil, looks at doped semiconduc‐ tor nanocrystals and composites of their potential toxicity and uses. This chapter summarizes the characterization of doped nanocrystals and composites; Ca-doped ZnO, Agand Eu-doped ZnO, and Ni-doped ZnO NCs; their biocompatibility; and applications and uncovers how these nanocrystals present desirable biocompatible properties, which can be useful as antitumoral and antimicrobial inducing agents, which differ markedly from toxic

The ninth chapter outlines a way of understanding "Toxicity of Titanate Nanosheets on Hu‐ man Immune Cells," which deals with the salient aspects of the influence of titanate nano‐ sheets in promoting well-being and health for human. Dr. Yasumitsu Nishimura and colleagues from Japan discussed the critical TiNSs material, which has the harmful potential to cause caspase-dependent apoptosis of human immune cells to the same degree as asbestos. The 10th chapter, by Dr. Magdalena Jedrzejczak-Silicka and Ewa Mijowska from the Labora‐ tory of Cytogenetics, West Pomeranian University of Technology, Poland, describes the

tions. Each of these endpoints discussed presents details in this chapter.

ceutical development process in the chapter.

properties observed in other general nanocrystals.

"General Toxicity and Its Application in the Nanomaterials Analysis."

rials might be limited.

VIII Preface

The book *Cytotoxicity* is an essential reading to all medical students, biologists, biochemists, and professionals involved in the field of toxicology. This book is a useful and ideal guide for novice researchers interested in learning research methods to study cytotoxic bioactive compounds.

#### **Assoc. Prof. Dr. Tülay Aşkin Çelik**

Adnan Menderes University, Art and Science Faculty Aydın, Turkey

**Section 1**

**Introductory Chapter**

**Section 1**

**Introductory Chapter**

**Chapter 1**

**Provisional chapter**

**Introductory Chapter: Cytotoxicity**

**Introductory Chapter: Cytotoxicity**

DOI: 10.5772/intechopen.77244

Cell cytotoxicity refers to the ability of certain chemicals or mediator cells to destroy living cells. The cytotoxicity is a very important aspect, as destruction of healthy living cells around the wound will have a negative impact on the healing process. Cytotoxicity is the general quality of being toxic to cells, and can be caused by chemical stimuli, exposure to other cells (NK or T cells for example), or physical/environmental conditions (radiation exposure, temperature or pressure extremes, etc.) [1]. Chemical toxicity can occur in many ways, but we hypothesize that it can be broadly classified into two major categories: disruption of specific biomolecular targets or pathways (e.g., receptor agonist/antagonist effects and enzyme activation/inhibition), or generalized disruption of cellular machinery that can lead to cell stress and cytotoxicity [2]. Chemical toxicity can arise from disruption of specific biomolecular functions or through more generalized cell stress and cytotoxicity-mediated processes. Chemical toxicity can occur in disruption of specific biomolecular targets or pathways (e.g., receptor agonist/antagonist effects and enzyme activation/inhibition), or generalized disruption of cellular machinery that can lead to cell stress and cytotoxicity. Cell-disruptive processes include protein, DNA, or lipid reactivity; physicochemical disruption of proteins or membranes (e.g., by surfactants); or processes such as apoptosis, oxidative stress response, mitochondrial disruption, endoplasmic reticulum (ER) stress, microtubule disruption, or heat shock response [2]. Treating cells with a cytotoxic compound can result in a variety of cell fates. By using a cytotoxic compound, healthy living cells can either be induced to undergo necrosis (accidental cell death) or apoptosis (programmed cell death). Whereas apoptotic cell death is slower, more orderly, and is genetically controlled, the cells may undergo necrosis, in which they rapidly loss membrane integrity and die rapidly as a result of cell lysis. The cells can stop actively growing and dividing (a decrease in cell viability). Cytostasis is a special category of cytotoxicity, wherein cells remain alive but fail to grow and divide [1]. Cell death/cytotoxicity cannot be the sole causal driver of this phenomenon. Some cytotoxicity may be driven by physicochemical factors, such

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

Additional information is available at the end of the chapter

Tülay Aşkin ÇelikAdditional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.77244

Tülay Aşkin Çelik

**1. Introduction**

#### **Chapter 1 Provisional chapter**

#### **Introductory Chapter: Cytotoxicity Introductory Chapter: Cytotoxicity**

#### Tülay Aşkin Çelik Tülay Aşkin Çelik

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.77244
