Methods for Assessing Neurotoxicity in Zebrafish - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 112

Chapter 10

Methods for Assessing
Neurotoxicity in Zebrafish

Chunqi Li, Wen Lin Seng, Demian Park, and Patricia McGrath
Phylonix, Cambridge, MA, USA

10.1 INTRODUCTION

Neurotoxicity, defined as an adverse effect on the structure or function of the nervous
system, can result from exposure to drugs used for chemotherapy, radiation treatment,
and organ transplantation as well as from food additives and environmental toxicants.
Neurotoxicity is the second leading cause (after cardiovascular toxicity) of drug
withdrawals. Examples of costly, high-profile drug withdrawals due to neurotoxicity
include diamthazole, vinyl chloride aerosol, and clioquinol (Wysowski and
Swartz, 2005). Neurotoxicity profiles of numerous approved drugs are incomplete
and many have been shown to cause neurotoxic side effects. For example, chlor-
amphenicol (an antibiotic) and ethambutol and isoniazid (antituberculosis drugs) can
cause optic neuritis (Chang et al., 1966; Noguera-Pons et al., 2005). Phenytoin (an
antiepileptic drug), fluorouracil and cytarabine (chemotherapy agents), and amino-
glycosides can induce cerebellar syndromes such as ataxia, dysarthria, and nystagmus
(Sylvester et al., 1987; Macdonald, 1991). Hormone replacement therapy (HRT) and
estrogen combined oral contraceptives (COCs) are known to induce stroke and
intracranial venous thrombosis (Bushnell et al., 2001; Nightingale and Farmer, 2004).
Antipsychotic drugs such as prochlorperazine can induce Parkinson's-like symptoms
(Nath et al., 2000; Catalano et al., 2005). Chemotherapy and anti-glycolipid anti-
bodies can induce peripheral neuropathy (Willison and Yuki, 2002; Cavaletti and
Marmiroli, 2004). In addition, the onset of demyelinating disease relapse has
been associated with vaccines (Kaplanski et al., 1995; DeStefano et al., 2003). Many
other drug-induced neurological complications such as cognitive impairment, head-
ache, and neuromuscular disorders have also been reported (Grosset and
Grosset, 2004).