1. Marine Pollutants: Heavy Metals

Metals are natural constituents of the Earth’s crust present in all ecosystems at variable concentrations. The use of metals has accompanied civilization since prehistoric times, characterizing the Bronze and Iron Ages, the Industrial Revolution, up to the present modern society, where they are closely linked to anthropogenic activities, including agriculture, transport, arts, and medicine ^[1][2]. Metals are found in the wires, batteries, and microchips, as well as in many common everyday objects. Although some heavy metals are crucial for life, their excess can be toxic and therefore extreme attention is paid to the possible consequences for human health and environment ^[1]. Because of their accumulation in the environment and their significant toxicity, many metals and metalloids have been identified as “priority substances” and included in the list of the Annex II of the European Directive 2008/105/EC (Annex X, Water Framework Directive 2000, https://echa.europa.eu/ann-x-priority-subs-water-dir-2000-60). In this regard, several metals, such as arsenic, lead, and mercury, have been included in the 2019 Substance Priority List by the Agency for Toxic Substances and Disease Registry (ATSDR) (https://www.atsdr.cdc.gov/spl/). Based on their chemical characteristics, the concentrations of metals are variable in the marine system and some metals tend to accumulate in the bottom sediments. Numerous species of marine invertebrates hyperaccumulate metals (such as arsenic, copper, iron, and zinc), thus resulting in significant relevance to human health and aquatic toxicity ^[3]. In depth analyses on the speciation, bioavailability, and bioaccumulation of some metals have been well described in other reviews ^[3][4][5].

Although many of the harmful effects that are induced by exposure of some heavy metals are well known, the mechanisms underlying their toxicity in humans have not yet been fully clarified. Numerous studies mainly conducted on fishes and mammals have highlighted the close correlation between exposure of heavy metals and neuronal damage ^[6][7]. Many of heavy metals can cross the blood brain barrier (BBB) and accumulate in the nervous tissues, inducing oxidative stress, inflammation, and metabolic dysfunction linked to the development of several neurodegenerative diseases.

Albeit the marine organisms are ideal indicators for long-term monitoring of metal accumulation ^[4], only few studies have been aimed to better understand the neurotoxic effects of heavy metals in marine invertebrates. Through in vitro and in vivo experiments, most of these studies have been focused on the analysis of the AChE activity as a possible biomarker of neurotoxicity in response to excess metals. Some studies have analyzed the combined neurotoxic effects of the different metals that are present in the polluted areas, while very few others have investigated the mechanisms underlying the toxicity that is induced by these substances at the neuronal level, including sensory alterations and neuromuscular dysfunctions.

Here, we focused our attention on neurotoxic effects that are caused by the exposure of some metals (see Table 1) in some marine invertebrates also having key positions in food chains.

Table 1. Neurotoxic metals and metalloid *.

Table 1 shows the classification of neurotoxic metals and metalloids in essential and not essential (modified from Caito and Aschner 2015). *Metalloid.

2. Marine Pollutants: Pesticides

Pesticides are chemical compounds that are specifically introduced into the environment to prevent, destroy, or control harmful organisms (pests) mainly in agriculture, including insects, rodents, fungi, and unwanted plants, as well as to block vector borne diseases in public health. They are also used for the protection of plants or plant products during their production, storage, and transport.

Although their application serves many important purposes, the very nature of pesticides is to damage unwanted organisms, posing great concern for a potential risk, even for non-target organisms. Indeed, many molecular targets of pesticides are shared between pests and non-target species, including humans, which may lead to a variety of adverse health effects. The over-use and/or misuse of pesticides is playing a negative role to the environmental health, affecting many aquatic and terrestrial species, as much to be now considered as contaminants of emerging concern (CECs), i.e., “new” pollutants in aquatic environments. Besides, the replacement of marine ingredients with plant material in the feeds used in fish farms introduces new unwanted substances in the marine environment, such as pesticides that are used in terrestrial agriculture, thus affecting not only fishes, but also other marine organisms ^[8]. Actually, based on all of these considerations, it is really very difficult to find the right balance between benefits and harms deriving from the use of pesticides.

Pesticides are divided into many subclasses, which are classified by the target organism (herbicides, insecticides, fungicides, and rodenticides) as well as by their chemical structure, physical state, and source of origin (i.e., botanicals). For the purpose of this review, we will focus on some classes of pesticides that are known for their neurotoxicity to marine invertebrate organisms, as, for example, organochlorines, organophosphates, and carbamates ^[9]. Organochlorines are synthetic pesticides, which belong to the group of chlorinated hydrocarbon derivatives, widely used in agriculture and chemical industry. Nowadays, many of the organochlorines have been banned in developed countries, as they are highly toxic and their characteristically long lifespan increases the risk of their accumulation in the environment ^[10]. Organophosphates and carbamates are organic molecules, with the first containing one or more phosphate ester groups, whereas the second is derived from carbamic acid. They are among the most widely used pesticides, which have been considered to be a less damaging alternative to organochlorines (together with carbamates), although they are known for their neurotoxicity, mainly targeting the cholinergic system. In particular, organophosphates and carbamate affect AChE activity by irreversibly binding the enzyme active site ^[11].

This entry is adapted from the peer-reviewed paper 10.3390/biology10020161