Certain species of bacteria, cyanobacteria, dinoflagellates, ciliates, raphidophytes, haptophytes, dinophyceaes, rhodophytes, diatoms and corals synthesize toxic compounds (e.g., biotoxins) (Botana et al., 2019; Vilariño et al., 2018). These molecules can modify the cellular process of other organisms, from plankton to humans. Harmful algae blooms (HAB) are defined as a group of toxic species present both, in freshwater and marine ecosystems. The presence of biotoxins in waters used for consumption, irrigation and recreational purposes represents a public safety concern, implicating also economic risks. Agricultural and aquaculture products are directly affected, altering the consumption of vegetables and animals. Therefore, many toxins are a serious threat to human health linked to poisoning after consumption of contaminated seafood, skin contact with contaminated water, or inhalation (Vilariño et al., 2018).

In the freshwater environment, cyanobacteria species are important producers of different types of cyanotoxins (Singh and Dhar, 2013). The sources and acute toxicities of cyanobacterial toxins, such as cylindrospermopsin (CYN), anatoxin-a (ATX-a), nodularin (NOD), and microcystins (MC), have been described (González-Jartín et al., 2020). On the other hand, marine biotoxins represent a diverse group that includes saxitoxin (STX), domoic acid (DA), ciguatoxin (CTX), yessotoxins (YTX), pectenotoxins (PTXs), brevetoxin (BTX), tetrodotoxin (TTX), okadaic acid (OA), azaspiracid (AZA), palytoxin (PLTX) and many other emerging toxins such as spirolides (SPX) (Otero et al., 2019; Krock et al., 2018; Vilariño et al., 2018). Even more, some of these toxins can be found in both ecosystems, marine and freshwater bodies.

Toxins alter photosynthetic organisms in different ways, such as decreasing the abundance of submerged plants and the diversity of aquatic plant communities (Burkholder et al., 2018). Biotoxins can also contribute to the inhibition of the net photosynthetic rate (Liang and Wang, 2015), alter the growth and development (McElhiney et al., 2001), and reduce the dry weight and the access to nutrients and oxygen (O₂) (Yamasaki, 1993). However, not much information has been described in terms of oxidative stress triggering in photosynthetic organisms caused by biotoxins. Recently, changes in oxidative and nitrosative stress associated with HAB have been described in invertebrates (González and Puntarulo, 2016, 2020).

A Special Report from the United Nations’ Intergovernmental Panel on Climate Change (IPCC) in September 2019 was the first IPCC statement to directly link HAB to climate change (Gobler, 2020). Therefore, climate change not only produces direct harm to aquatic organisms but can also modify the distribution and intensity of multiple co-stressors within marine and freshwater ecosystems (Griffith and Gobler, 2020). Also, water pollution and eutrophication contribute to making more intense and frequent the blooms of biotoxin producers. The increment in frequency and magnitude of the HAB phenomena is evident all over the world (Gobler, 2020; Wells et al., 2015). Surprisingly, Krock et al. (2020) reported the presence of a phycotoxin produced by the dinoflagellate Dinophysis sp. in Antarctic waters. Hernando et al. (2018) and Wells et al. (2015) have associated climate change with alterations in the structure and composition of some phytoplanktonic communities, suggesting a prevalence and geographical spread of HAB. Therefore, climate change would lead to an overproduction of biotoxins by many photosynthetic species (Botana et al., 2010).

Widespread information alerts that this increased availability of biotoxins both in freshwater and seawater environments, could have an impact on the trophic chain in terms of alterations in the oxidative balance in many photosynthetic organisms of the aquatic community. It was reported that several biotoxins, such as MC, CYN, STX, and NOD, are found dissolved in freshwater environments (Doucette et al., 2018); thus, the effects on microalgae and vascular plants were studied. On the other hand, NOD and DA can be found dissolved in marine waters due to their hydrophilic nature (Doucette et al., 2018), and their effects were analyzed in marine macro and microalgae. Based on this information, the objective of this review was to assess how these biotoxins are implicated in the generation of oxidative and nitrosative metabolic changes from not only biotoxin-producing organisms but also from non-producing organisms and therefore modifying the oxidative cellular balance of several other species.

The generation of reactive O₂ species (ROS), such as superoxide anion (O₂⁻), hydrogen peroxide (H₂O₂), and hydroxyl radical (^•OH), takes place continuously in living cells, mainly as a byproduct of respiration (Abele and Puntarulo, 2004). They may particularly damage targeting proteins, lipids, and nucleic acids, often leading to cumulative injury (Lushchak, 2011). Harmful effects of ROS generation are due to the increase in their steady-state concentration either by the enhancement of their production rates and/or the decrease of the antioxidant activity.

In freshwater and marine areas of elevated biological productivity, such as phytoplankton blooms, biological production of ROS can be a substantial and dominant ROS source, especially of O₂⁻ and H₂O₂ (Diaz and Plummer, 2018; Marsico et al., 2015; Rusak et al., 2011). Many phytoplankton taxa also produce extracellular ROS under optimal growth conditions in culture. Extracellular ROS production has been quantified in at least 21 eukaryotic phytoplankton species. The majority of these species are capable of triggering HAB (Diaz and Plummer, 2018). Harmful algae species generate much more extracellular ROS than any other phytoplankton taxa. Some biotoxins, like MC, are known to have positive effects as protective elements against reactive species. Therefore, the capacity of some cyanobacteria to produce MC may be a potential selective factor in competing with non-MC-producing strains. This fact was already observed in nitrogen-limited and UV B radiation conditions (Ding et al., 2013). It has been shown that MC prevents oxidative stress (Van de Waal et al., 2011; Zilliges et al., 2011). Recently, Malanga et al. (2019) presented the first in vitro report of the role of MC as an antioxidant for hydrophilic radicals, suggesting that ascorbyl (A^•) and ^•OH radicals could be efficiently quenched by the administration of [D-Leu1] MC-LR.

On the other hand, some raphidophytes species and the dinoflagellate Cochlodinium polykrikoides are known to generate ROS (Kim et al., 1999a; Twiner and Trick, 2000), which can have adverse effects on aquatic organisms. The raphidophyte Chattonella marina generates ^•OH, and its small and large verruciform protrusions on the cell surface are probably involved in the production of O₂⁻ (Kim et al., 1999b; Shimada et al., 1993). Extracellular ROS production by the harmful bloom-forming phytoplankton species C. marina has been implicated in its toxicity (Kim and Oda, 2010). All raphidophytes that produced ROS inhibited the growth of the marine bacterium Vibrio alginolyticus (Oda et al., 1992). The production of small quantities of H₂O₂ has also been detected in the dinoflagellates Prorocentrum micans and Akashiwo sanguinea (Daugbjerg et al., 2000), and high reactive species concentrations were found in stressed Alexandrium tamarense (Jauzein and Erdner, 2013). The production of ROS by microalgae appears to principally affect fish (Ishimatsu et al., 1996); however, other organisms may also be disturbed. Some fish mortalities may be attributable to the production of brevetoxin-like compounds, to ROS, or a combination of both. Reactive species contribute to pathological changes in the gills of fish, and the brevetoxin-like neurotoxins impair cardiac function (Endo et al., 1992). During plant photosynthesis and metabolism ROS are also generated and are increased in plants exposed to environmental stresses (Dring, 2006).

As it will be shown in this review, the magnitude of the oxidative stress and the specific mechanism of cytotoxicity depend on parameters related to both the photosynthetic species and the factors related to the biotoxin features (Fig. 1). Thus, oxidative stress studies should be faced taking special attention to the organism and the tissue under consideration, as well as the type, concentration, and exposure time to the biotoxin.

Alterations of the environmental conditions, such as increases in nitrate (NO₃⁻), phosphate (PO₄³⁻) and Fe nutrients, among other factors, are important contributors for the increasing global occurrence of biotoxins blooms (Heisler et al., 2008; Fisher et al., 2006). These blooms would be responsible for releasing biotoxins and increasing ROS in the aquatic environment, where photosynthetic organisms in contact with them will face metabolic changes.

Toxins may reach photosynthetic organisms through different pathways. Aquatic macrophytes and microalgae are naturally into direct contact with these toxins not only in eutrophic water bodies but also seasonally when environmental conditions favor the development of toxic blooms. On the other hand, terrestrial plants are exposed to cyanotoxins via contaminated soils or the irrigation water taken from polluted sources (Chen et al., 2010). The main MC uptake route for P. australis appeared to be the stem and rhizome, from which the toxin is transported into the higher parts of the plant to the leaves (Pflugmacher et al., 2001). The CYN was mainly absorbed by the roots of O. sativa to be further translocated into the leaves (Prieto et al., 2011). In marine organisms, for instance, detectable concentrations of NOD were observed in different tissues of F. vesiculosus, especially in the stem and basal parts (Pflugmacher et al., 2007).

Little information is available about the specific cell targets of biotoxins on photosynthetic organisms. However, it is generally known that the toxic mechanism of MC and NOD is the inhibition of protein phosphatases 1 and 2A in plant cells (Pereira et al., 2011; Peuthert et al., 2008). It is also recognized that CYN may act through the inhibition of GSH and protein synthesis (Froscio et al., 2001; Froscio et al., 2008), but the process may be mediated by cytochrome P-450 generated metabolites (Humpage et al., 2005). Moreover, STX acts as a potent blocker of sodium channels in nerve axons of vertebrates, and its neurotoxicity and potentially lethality were observed in mice and fishes (Falconer, 2008). However, algae are much more resistant to STX than animal cells (Perreault et al., 2011).

The diagram in Fig. 3 summarizes a possible chain of events triggered by global climate change. An alteration in the aquatic community composition through modification in the oxidative and nitrosative metabolism in the organisms could be produced by the enhancement in the magnitude and frequency of HAB. On the other hand, as previously mentioned, some biotoxins (e.g., MC) could show some protective effects from reactive species damage. Thus, they can act as a potential selective factor favoring MC-producing blooms, as compared to non-toxic species development under the same conditions.

Based on the actual information available, it seems that the oxidative stress related to the HAB is a critical component of the mechanisms triggered by climate global change. Thus, the antioxidant defense system of photosynthetic organisms is a key feature to manage the damage produced by biotoxins and could be part of the adaptive process. The ability of each species to cope with this hazardous natural condition would allow the adaptation to the new scenario or provoke the organism’s injury/death. The difference, in terms of survival, will be granted by the antioxidant response and the triggering of signaling pathways to express protection mechanisms. It is evident from these data that the biotoxins promote oxidative stress, not only in higher plants but also in algae, independently of their habitat (marine, freshwater, or soil). Therefore, the triggering of oxidative stress seems to be a common occurrence in photosynthetic organisms that respond with similar behaviors. Thus, the metabolic responses may modify the community composition leading to alterations in the global health of each habitat, risking the survival of many species with ecological relevance and economical outbreaks. The available data that explore global change-dependent effects, in terms of oxidative stress due to biotoxin exposure of photosynthetic organisms, especially in marine algae, is scarce up to now. Further studies are required to assess the role of the antioxidant enzymes in the photosynthetic cells exposed to biotoxins in their natural environment.

Future research will need to be focused on clarifying the information on the in situ effects of the changes in the HAB over the antioxidant ability of many photosynthetic communities. Also, the signaling pathways leading to the protection mechanisms observed should be studied. It is important to mention that the nitrosative metabolism implication in this field has not been explored yet. Even though oxidative and nitrosative actions are not the only way biotoxins lead to deleterious alterations on the organisms, their impact on the overall cellular damage is far from being characterized. Clarifying these effects could be a key factor for future advances in this field and could help to design strategies to improve the natural ability of plants and algae to cope with a growing challenge such as global climate change.