The enzymatic defense constitutes an array of enzymes that neutralize various specific ROS functions (Sies, 2015). Superoxide dismutase (SOD), the first line of enzymatic defense, dismutates superoxide radicals to H₂O₂ and H₂O. The produced H₂O₂ is subsequently neutralized by another enzyme called catalase (CAT). The organic hydroperoxides are outraised by an enzyme called glutathione peroxidase (GPx). Water molecule is released in the process. For the action of GPx, a reduced glutathione (GSH) is consumed, which in turn is converted into oxidized glutathione (GSSG). The GSSG is then returned to its reduced form (GSH) by the enzyme glutathione reductase (GR). Glutaredoxin system also uses the reduction state of the glutathione to preserve and control the cellular redox cellular homeostasis and redox-dependent signaling pathways (Figure 2). The Keap1-Nrf2-ARE ((Kelch-like ECH-Associating protein 1) nuclear factor erythroid 2 related factor 2-antioxidant response element) regulates the signaling pathways for the transcription of the antioxidant enzymes (Hybertson et al., 2011; Mishra et al., 2019; Huang et al., 2021; Li et al., 2021; Paital et al., 2022).

Unlike the enzymatic redox regulatory/antioxidant molecules, several non-enzymatic antioxidant molecules can directly and non-specifically neutralize the chemical nature of various ROS. These antioxidants are usually dietary in source in higher animals, whereas in lower animals and in some of the fishes, small antioxidants such as ascorbic acid are synthesized (Jones, 2008). The capacity for synthesis of ascorbic acid is lost in evolution in higher animals because of the absence of the enzyme L-Gulonolactone oxidase or L-Gulonolactone synthase. Besides ascorbic acid (vitamin C), other small non-enzyme antioxidants are GSH, vitamin A (retinol, β-carotene), vitamin E (tocopherol), polyphenolic compounds, etc. It is to be noted that all the above antioxidants work alone or in cascade to protect the cell from the toxic action of ROS, failing to which the cell experience oxidative stress, which is evident in animals, including fishes (Bal et al., 2022a; Bal et al., 2022b). Any external or internal stress including exposure to pollutants, toxicants, chemicals, microplastics, food availability, etc also generate more ROS to develop oxidative stress in fishes (Thakur et al., 2022). It is to be noted that higher levels of oxidative stress can hamper growth, production, reproduction, etc in animals, including fish. Therefore, the above factors can be considered to monitor the health status of (aquatic) animals in general and fish in particular under any stress, including microplastics, pesticides, and toxic nano-particles (Panda et al., 2022a; Panda et al., 2022b; Pati et al., 2022a; Pati et al., 2022b; Panda et al., 2023).

Oxygen acts as the precursor for the generation of ROS. Superoxide radical (O₂˙^─) is produced with the first electron reduction of oxygen. The produced O₂˙^─ is converted into H₂O₂ by the enzyme superoxide dismutase (SOD), H₂O_{2 or} hydroperoxides are neutralized by the enzyme catalase (CAT) or glutathione peroxidase (GPx), respectively. GPx uses one molecule of the reduced glutathione (GSH) by the process, and the produced oxidised glutathione (GSSH) gets back to GSH by the enzyme glutathione reductase (GR). GR uses one molecule of NADPH in the process and NADP + produced by the process is reduced back to NADPH by the enzyme Glucose-6-phosphate dehydrogenase (G6PD). The enzyme glutathione-S-transferase (GST) also neutralizes xenobiotics with the help of GSH. Small antioxidants such as ascorbic acid, vitamins A, E, etc., can directly neutralize ROS non-specifically (modified after Paital, 2018b).

Plastic additives are tiny plastic particles or stabilizers added to various consumer products, such as personal care products, cleaning agents, and cosmetics, to provide specific properties or functions (Koelmans et al., 2019; Chokwe and Okonkwo, 2019). These additives can be composed of various plastics, such as polyethylene, polypropylene, and polystyrene, and can take different forms, including microbeads, microfibers, and microgranules (Ramachandraiah et al., 2022). Plastic additives can enter the environment through various pathways, including wastewater discharge, stormwater runoff, and accidental spills (Yusuf et al., 2022). Marine animals can also ingest plastic additives and accumulate in the food chain, a hazard to human health (Rochman et al., 2019). People who regularly eat seafood may ingest up to 11,000 microplastic particles annually (Cox et al., 2019). Plastic additives can cause oxidative stress in fish through a variety of mechanisms. One such mechanism is the release of chemicals from the microplastics that can disrupt the balance between levels of ROS and antioxidants in the fish (Chae and An, 2020). Another mechanism is the physical damage to fish tissues, leading to inflammation and increase in ROS production (Su et al., 2020).

Plastic additives ingestion can cause damage to fish organs, including the liver, kidney, and gut. Plastic exposure causes stress on the liver cells of zebrafish embryos and crucian carp (Li et al., 2018; Yang et al., 2020). Additionally, plastics have been exposed to accumulate in the gut of fish, which can lead to physical damage and inflammation (Brennecke et al., 2016). Fish that have ingested plastic additives can also exhibit behavioral changes. Chen et al. (2020) and Qiang and Cheng, 2019 found that plastic additives resulted in alterations in the swimming behavior of zebrafish and juvenile yellow perch feeding behavior, respectively. These behavioral changes can negatively impact fish survival and reproduction, as they change the behavior of fish for reproduction (mating), to avoid predators, and to find food. Plastic additives affect the immune system of fish by overexpressing the immune-related genes in zebrafish and Japanese medaka (Huang et al., 2021a; Liu et al., 2022).

According to Adeleye et al. (2014), plastic additives may contain additional water pollutants that can be additive factors to cause fish oxidative stress. Studies have indicated that microplastic additives have the ability to induce oxidative stress in fish, as demonstrated by several research studies. For instance, Boháčková et al., 2023 observed that rainbow trout exposed to plastic additives experienced a noteworthy increase in oxidative stress biomarkers. Another study by Wang et al., 2019 found that exposure to plastics led to oxidative damage in the liver tissues of zebrafish. Plasticizers are plastic additives that can be liberated into the environment under these circumstances; Iheanacho et al. (2020) exposed Clarias gariepinus to plastic additives (melamine formaldehyde, polyvinyl chloride, melamine) and observed the generated neurotoxicity and oxidative stress in the exposed fish as compared to the control groups. In addition, the fish experienced liver damage, as indicated by increased levels of AST and ALT and hypoproteinemia. Dietary intake of polyvinyl chloride caused oxidative damage in Dicentrarchus labrax (European sea bass), leading to impaired immune activities (Espinosa et al., 2018). Barboza et al. (2018a) found that water with microplastics shows an increase in mercury levels in the liver and gills of Dicentrarchus labraxjuveniles. Mercury and the microplastics, alone and in mixtures, caused oxidative stress in the liver and gills.

Zitouni et al. (2021) discovered the existence of various plastic additives in the tissues of Dicentrarchus labrax, such as plasticizers, fiber-reinforced plastics, curing agents, flame retardants, and heat stabilizers. The study confirmed the presence of 68 different additives, with the primary additive being an organic PVC stabilizer, followed by a DLC 785 lubricant with a diamond-like carbon coating. PEVA was found to be the most common tissue microplastic type, followed by PA, among the four polymer types identified by the researchers. In contrast, Alomar et al. (2017) observed no signs of oxidative damage in the Mullus surmuletus’ liver after microplastic ingestion, indicating that the ingestion level was possibly too low to cause harm. However, they did detect a slight increase in GST activity, indicating that the low levels of microplastics may trigger the activation of the detoxification process in response to the low levels of microplastics (Table 1).

Fish is a valuable nutrient-rich food in the human diet. However, consuming microplastic-contaminated fish can be a potential health hazard, especially in areas where fish is a significant dietary staple or regions heavily polluted with these minute particles (Barboza et al., 2018b). In a recent study by Schwabl et al. (2019), the presence of microplastics was detected in human stool samples for the first time, suggesting that these particles are ingested and excreted by humans. The retention and elimination of microplastics within the body can be influenced by several factors, such as their shape, polymer type, size, surface charge, and chemistry, as well as any additional chemicals present in the microplastics ingested (Smith et al., 2018). Upon ingestion, the body can assimilate microplastics, and their cellular uptake can interact with proteins, phospholipids, and carbohydrates and cause adverse effects. Similar to nano-plastics, the absorption of microplastics is heavily dependent on their interactions with biological matter (Lehner et al., 2019). EFSA Panel on Contaminants in the Food Chain, 2016 has proposed that the human body can uptake only microplastics with a size lesser than 150 μm. Further investigation is needed to fully comprehend the mechanisms underlying microplastic absorption.

Microplastic exposure can trigger toxicity pathways, such as oxidative stress and inflammation. After ingestion, microplastics may affect a specific area or enter the blood and reach several organs and tissues. Moreover, microplastics bioaccumulate in the human body and exerts toxicological effects (Ferrante et al., 2022). Microplastics trigger ROS production through mitochondrial damage or by increasing the immune system responses while neutralizing harmful foreign particles (Yang et al., 2020). Microplastic contamination produces oxidative stress in proteins, lipids, and DNA by altering the antioxidant defense mechanisms (i.e., CAT, SOD, GST, GPx, and GSH) at the catalytic and transcriptional levels. In biological systems, microplastics deregulate the gene expression that controls oxidative stress. Thus, microplastics act as pro-oxidant stimuli, activating antioxidant gene expression through an Nrf2-dependent mechanism in marine vertebrates and invertebrates. These alterations are responsible for the induction of oxidative stress, neurotoxicity, immunological responses, endocrine system disruption, reproductive abnormities, genomic instability, embryotoxicity, and trans-generational toxicity (Alimba and Faggio, 2019).

Tang et al. (2018) observed that microplastic exposure in seabream heads altered the JNK (c-Jun N-terminal kinase) and ERK (extracellular signal-regulated kinase) signaling pathways which are involved in the detoxification process of fish. Polyvinylchloride and polyethylene exposure resulted in NRF2 upregulation, which led to oxidative stress in the renal primary leucocytes of seabream heads (Espinosa et al., 2018). Cocci et al. (2022) studied the polymers present in the gut of red mullet and the European hake as polyethylene and polypropylene. Microplastic abundance is positively correlated with antioxidant enzymes (catalase and superoxide dismutase) and cytokines (interleukin-1β, 10, and interferon) levels, causing ROS generation and immune cell infiltration in the gut. Their study found that microplastics affect fish gut through the induction of cytokine-dependent signaling pathways. Oxidative stress induced by microplastics mediates endoplasmic reticulum stress, leading to liver apoptosis. High concentration of polystyrene microplastic exposure in golden pompano (Trachinotus ovatus) caused oxidative damage and upregulation of genes (Grp78, Xbp-1, Eif-2α, and chop), resulting inendoplasmic reticulum stress (ERS). Severe oxidative stress raised the BAX/BCL-2 ratios and induced cell death (Yao et al., 2023).

Polystyrene microplastics affected the immune system of carp (Cyprinus carpio) and triggered the TLR2 signaling pathway. The study revealed that the mRNA and protein expressions of TLR2, COX2, TNF-α, tumor necrosis factor receptor-associated factor 6 (TRAF6), IL-1β, NF-κB, iNOS, and p65, were increased in hepatopancreas and hepatocytes of carp (Cui et al., 2023). Wang et al. (2022) found that extended exposure to polystyrene microplastics in loach juveniles (Paramisgurnus dabryanus) inhibited the expression of Keap1-Nrf2 signaling pathway genes in loach juveniles. Polystyrene microplastic exposure induced apoptosis by upregulating p53, gadd45ba, and caspase3b expressions. They also upregulated TNF-α and PTGS2A, which are important gene markers in the inflammatory mechanism in zebrafish (Umamaheshwari et al., 2021b). Qiang and Cheng. (2021) found that sub-chronic exposure to polystyrene in zebrafish resulted in enhanced ROS production in the ovary and testis, as well as lowered spermatocyte count. Additionally, male gonads showed an increase in apoptosis (BAX, p-53, caspase 7, 8, and 9) and a decrease in the thickness of the basement membrane. Long-term (35 days) exposure to polystyrene microplastics altered the metabolic pathways and gene regulatory patterns brought on by the production of ROS and oxidative stress in the same species (Umamaheshwarri et al., 2021a).

Polyethylene microplastics elevated the expression of BAX, p53, NF-κB, p65, IKKα, IKKβ, caspase-3, and 9 genes in the gills of carp. An important innate immunity element, NLRP3 (nucleotide-binding oligomerization domain-like receptor protein 3) inflammasomes was overactive. TNF-α, IFN-γ, IL-2, IL-6, IL-8, IL-1β, which cause immune disorders, increased, while IL-4 and IL-10, anti-inflammatory factors, decreased significantly. Thus, NF-κB pathway triggered oxidative stress, apoptosis, and NLRP3 inflammasome to promote inflammatory, immunological responses (Cao et al., 2023). Santos et al. (2022) studied the combined exposure of microplastics with copper (Cu) heavy metal in zebrafish (Danio rerio) gills. In the combination group (Cu25 + MPs), oxidative stress and lipid peroxidation were induced due to the inhibition of CAT and GPx activities in gills of zebrafish. Further, an upregulation of caspase-3 and tph1a (tryptophan hydroxylase 1a) genes and a downregulation of apoptosis and serotonin synthesis were also observed (Figure 4).

So, it can be summarized that the negative impacts of microplastics on fish growth and survival rates can have significant consequences for fish populations and the larger ecosystem. Reduced population sizes can affect aquatic ecosystems’ overall productivity and fish availability for human consumption.

Several studies have described that insecticide exposure in fish leads to oxidative stress. Imidacloprid and propoxur are insecticides that, in combination, induced oxidative damage and inhibited AChE activity in the neotropical fish, Rhamdia quelen. Increased catalase activity and altered antioxidant capacity against peroxides (ACAP) and thiobarbituric acid reactive substances (TBARS) confirmed the oxidative stress in the brain, gills, muscle and liver of the tested fish (Marins et al., 2021). Gonçalves et al. (2018) evaluated the oxidative stress biomarkers in the muscle, brain, gill and liver of Astyanax jacuhiensis in exposure to carbamate propoxur. There was an increase in the activity of GST in the liver and gills and protein carbonyl (PC) in the brain, whereas AChE activities were reduced in the brain and muscle. Similarly, combined exposure of lambda-cyhalothrin and imidacloprid in the gills and liver of streaked prochilod (Prochilodus lineatus) increased protein carbonylation and LPO level. Lambda-cyhalothrin was the most toxic insecticide, even at much lower concentrations than imidacloprid, causing DNA damage in the fish’s gills, liver, and brain (Alvim and dos Reis Martinez, 2019; Figure 5).

Pyriproxyfen (PPF) is a well-known synthetic insecticide used to control various insect species affecting crops in agricultural fields. Li et al., 2022a studied PPF exposure in Labeo rohita fish and found increased DNA damage in multiple tissues. The results showed increased oxidative stress indicators (ROS and TBARS) and antioxidant enzymes (GRd, SOD, peroxidase, and catalase) in several fish tissues. They recorded A decrease in the activity of different antioxidant enzymes in treated fish. Chlorpyrifos exposure in Clarias gariepinus elevated stress markers (glucose and cortisol), testosterone, luteinizing hormone, serum AST and ALT levels. CPF reduced total serum protein, lysozyme, follicle-stimulating hormone, AChE, albumin, estradiol hormone, and immunoglobulin activity levels while increasing hepatic DNA damage. CPF also induces oxidative stress in renal and hepatic tissues (Mansour et al., 2022).

Cypermethrin (CYP), a pyrethroid pesticide, increased the production of SOD, CAT, and malondialdehyde (MDA) in zebrafish embryos. In addition, changes in acetylcholine esterase, nitric oxide content, and Na⁺/K⁺-ATPase activity were observed. These changes disrupted cardiac development and ion regulation (Gupta et al., 2023). Acute deltamethrin exposure elevated malondialdehyde levels and lowered catalase enzyme. Initially, T-AOC and SOD levels were raised and then dropped. Being exposed to hypoxic conditions, deltamethrin exposure significantly reduced the survivability of crucian carp by lowering oxygen uptake, promoting lactate accumulation, and altering energy metabolism. Additionally, histological assays confirmed that deltamethrin caused apoptosis and gill damage under hypoxic conditions. Deltamethrin exposure induced oxidative and ER stress, which resulted in the impairment of hypoxic resistance of Carassius auratus (crucian carp) (Yuan et al., 2023). Phorate exposure to the kidney and liver of Channa punctatus caused an increase in the expression of apaf-1 (apoptotic peptidase activating factor-1), p53, and CAT. Thus, phorate-induced apoptosis, oxidative and DNA damage in Channa punctatus (Ratn et al., 2017).

Herbicides used in fields leach into nearby natural resources and bring about detrimental changes in aquatic life (Table 4). Acetochlor exposure in bighead carp increased DNA damage and resulted in oxidative damage. The cellular protein concentration was lower in gills, liver, brain, and kidneys of treated fish than in unexposed fish (Mahmood et al., 2022). Broadleaf weeds that compete with the nutrition uptake of agricultural crops are removed by continuous application of Pendimethalin, an herbicide. Pendimethalin causes toxic effects by disrupting the physiological and hematobiochemical reactions of fish. Exposure to pendimethalin in bighead carp (Hypophthalmichthys nobilis) will have a great impact on the physical and physiological activities of fish as reflected by abnormal behavior, loss of equilibrium, erratic swimming, air gulping, increased surface breathing, mucus secretion and fin tremors. The data showed that pendimethalin-exposed fish had increased serum LDH, ALT, and AST enzyme activity levels (Wang et al., 2022).

Glyphosate-induced neurotoxicity and increase in anxiety in adult zebrafish. There was an increase in dopamine and serotonin levels. Downregulation of gene expression in the dopaminergic system, namely th1, th2, comtb, and scl6a3, was observed along with the elevated levels of enzymic antioxidants, CAT and SOD, which led to a decline in the glutathione reserves. All these responses evoked in the antioxidant defense mechanisms, and these results were also due to oxidative stress and lipid peroxidation observed in the fish brain (Faria et al., 2021). Dicamba (DIC) and 2,4-dichlorophenoxyacetic acid (2,4-D) are auxinic herbicides used to control weeds in agriculture. DIC and 2,4-D exposure induced oxidative damage at purine levels in Cnesterodon decemmaculatus. Herbicide-exposed fish revealed increased CAT and GST activities and decreased GSH content. Additionally, diminished AChE activity and total protein content were observed (Es Ruiz de Arcuate et al., 2019).

Fungicides are most widely and extensively preferred among the various agricultural pesticides. Amidst the diversified range of fungicides available, difenoconazole is generally used triazole fungicide in the production of agricultural crops. In carp, difenoconazole exposure might cause ROS production resulting in oxidative stress with increased MDA levels and subsequent decline in the activity level of enzymatic antioxidants such as CAT, SOD, and GPx (Wu et al., 2023). Nataraj et al. (2023) studied the effects of difenoconazole exposure in Labeo rohita. Among the various organs of Labeo rohita, such as gill, liver and kidneys examined for their antioxidant efficiencies, a significant reduction in the activities of SOD and CAT was observed in comparison with the control fish. In addition, GST activity and LPO level were found to be more in the vital tissues of the carp. A drastic change in the gill histology of the carp due to difenoconazole exposure caused hypertrophy, epithelial lifting, epithelial necrosis, and lamellar fusion. Furthermore, the presence of pyknotic nuclei was a significant and noticeable change in both the liver and kidney. Further, dysfunctions like cellular edema, shrinkage of glomeruli, vacuolation, and tubular necrosis occurred in the liver of Labeo rohita. Obvious DNA damage with prominent tail formation occurred in a time and concentration-dependent manner. Crupkin et al. (2021) reported that azoxystrobin fungicide caused genotoxicity and oxidative stress in Australoheros facetus. In conjunction with this, inhibition of SOD occurred in the liver and gills of juvenile fish.

The global use of folpet as a fungicide has been widespread for the past 50 years. Folpet exposure in common carp (Cyprinus carpio) for 14 days showed a significant reduction in RBC, hemoglobin levels, hematocrit values, and increased activity of antioxidant enzymes (CAT, SOD, GPx) along with HSP70 genes. Besides its impact on the blood cells, folpet also causes DNA damage and oxidative stress (Acar et al., 2023). Pyraclostrobin (PYR), a strobilurin fungicide, poses a potential risk to aquatic organisms as it promotes ROS and MDA content in hepatopancreas of organisms. PYR-exposed aquatic lives showed enhanced expressions of the genes p38, JNK MAPK, HSP70, and HSP90. Remarkable reduction in the antioxidant enzymes and biomarkers levels, upregulation of BAX, APAF-1, Caspase-3, and 9, and downregulation of BCL-2 in carp hepatopancreas upon exposure to pyraclostrobin. Inflammatory response of the exposed fish showed changes in the IL-1β, IL-6, TNF-α, TGF-β, NF-κB, and p65 and immune parameters (IgM, LYZ, ACP, C3, and AKP), indicating that PYR exposure caused an induction in apoptosis due to oxidative stress and also evoked inflammation and immunotoxicity in common carp (Zhao et al., 2022).

The above-cited studies reveal that pesticides entering aquatic environments affect fish health by inducing oxidative stress, immunotoxicity, and inflammatory responses. Pesticides also cause behavioral changes and organ damage in fish. This affects fish’s growth, reproduction, and nutritional quality, making it a non-profitable and non-consumable product. All these changes depend upon the pesticides’ exposure duration, concentration, and chemical structure. Aquatic systems may contain pesticides as a result of anthropogenic or natural causes. Moreover, consuming pesticide-contaminated fish has a direct impact on human health. Fish containing pesticide residues has the potential to cause health problems in humans, such as epilepsy, somatic growth dysfunction, cancer, genetic damage, liver and kidney dysfunction, leukemia, decreased fertility, teratogenesis, and suppression of the immune system (Hoque et al., 2022). Some studies reported that the consumption pesticide contaminated fish does not affect human health much. However, potential long-term exposure can result in causing various ailments in humans (Chang et al., 2020; Tyohemba et al., 2021).

Pesticides can cause oxidative stress and carcinogenesis in fish. Long-time exposure to malathion pesticides in fish increased the expression of tp53 and its related genes, which in turn activated theatm/atr gene expression. The hif-1 gene showed an increase in expression, but the Ras (a proto-oncogene) was unaffected. The continuation of this condition downregulated BCL2 levels, and the BCL2/bax ratio resulted in an apoptotic response (de Souza et al., 2023). In grass carp (Ctenopharyngodon idellus), the neonicotinoid chemical imidacloprid (IMI), which is commonly used in agricultural production, induced mitochondrial dysfunction, which led to inflammation and an increase in NF-kB, TNF, IL-1, and IL-6 (pro-inflammatory genes) expression. IMI exposure triggered apoptosis by encouraging the release of Cyt-C (cytochrome-C), BCL-2 downregulation, and BAX, Caspase 3 and 9 upregulation. IMI exposure also caused the expression of BNIP3, LC3B, and P62 (mitophagy-related genes). The study results reveal IMI-induced inflammation, mitophagy, oxidative damage, and mitochondrial apoptosis in the hepatocytes of grass carp through the NF-kB/JNK pathway (Miao et al., 2022).

In carp, avermectin disrupted the blood-brain barrier and promoted apoptosis, inflammation, neurotoxicity, and oxidative damage involving the NF-κB and PI3K/Akt signaling pathways. Avermectin also increased IL-1β, IL-6, TNF-α, and iNOS, resulting in brain inflammation (Zhang et al., 2022). Difenoconazole (DFZ) is a long-lasting fungicide in the marine environment. DFZ altered the expressions of p53, FAS, BCL-2, BAX, Caspase3, 8 and 9. SOD, CAT, and GPx were down-regulated, and the NF-κB signaling pathway was activated in the spleen tissue of Cyprinus carpio. An increase in Il-6, Il-1β, and TNF-α (pro-inflammatory cytokines) and a subsequent decrease in Il-10 and TGF-β1 (anti-inflammatory cytokines) were observed. DFZ exposure damaged the carp’s spleen tissue by inducing oxidative stress, apoptosis, inflammatory responses, and immunosuppression (Liu et al., 2022). Enrofloxacin is a type of fluoroquinolone that has high risks to aquatic organisms. The effects of ENR exposure in Pelteobagrrus fulvidraco’s (yellow catfish) gills, reduced Na⁺/K⁺-ATPase activity and impaired immune system. Meanwhile, ENR induced oxidative stress, apoptosis, and MAPK signaling at higher concentrations (Xu et al., 2022).

In common carp kidneys, chlorpyrifos inhibited the miR-19a, which enhanced AMPK (AMP-activated protein kinase). Chlorpyrifos exposure enhanced the expression of apoptosis and autophagy-related genes such as TSC complex subunit 2 (TSC2), BAX, light chain 3 (LC3), p53, Dynein, Caspase-3, and 9. Exposure to chlorpyrifos reduced the expressions of Rheb (Ras homolog mTORC1 binding), BCL-2, and mTOR (mechanistic Target of Rapamycin). Thus, CPF promoted autophagy, oxidative damage, and apoptosis in the experimental fishes more than the control fish group (Zhang et al., 2019). Zhao et al. (2021) found that CPF exposure in largemouth bass (Micropterus salmoides) caused an increase in IL-8, TNF-α, and IL-15 and a decrease in TGF-β1 and IL-10. CPF exposure also promoted overexpression of Caspase-3, 8, 9, and BAX which resulted in apoptosis. According to Li et al. (2022c), using acetochlor herbicide on grass carp caused an increase in the levels of BAX, Beclin1, LC3B, P62, and Caspase 3 expression while reducing the expression of BCL2. Additionally, the study revealed a rise in ROS levels and a decrease in PPAR/RXR pathway expressions following acetochlor treatment. As a result, acetochlor exposure led to a cascade of apoptosis via the BCL2/BAX/Casp3 pathway and Beclin1-dependent autophagy, which was triggered by ROS-mediated PPAR/RXR inhibition. TNF-α, Il-6, Il-1β, and iNOS were increased with the use of difenoconazole fungicide, while the transcription level of TGF-β1 and Il-10 was inhibited. According to Wu et al. (2023), using the product led to an increase in BAX, p53, Caspase-3, and 9. Meanwhile, the BCL-2, Capsase-8, and FAS were inhibited. Furthermore, there was a noticeable increase in LC3II protein expression levels and the atg5 (autophagy-related gene), while the transcript levels of p62 were found to be decreased. This suggests that the use of the product stimulated autophagy (Figures 6, 7).

Li et al. (2021) studied how both cypermethrin (CMN) and sulfamethoxazole (SMZ) in combination affected grass carp. They revealed that the first 30 genes controlled by CMN and SMZ were involved in pathways that were closely related. Moreover, the combined exposure group experienced greater imbalances in oxidative stress index than the single exposure group. In addition, activation of the NF-κB signaling resulted in an immuno-inflammatory response in the combined exposure. Feng et al. (2023) reported exposure to abamectin pesticide-induced respiratory system toxicity in carp by activating the PI3K/AKT/mTOR pathway and inhibiting autophagy, resulting in oxidative stress, inflammation, and apoptosis; Yuan et al. (2023) found that high concentrations of deltamethrin insecticide led to the downregulation of Nrf2 signaling and its related genes (CAT, SOD, and GPX1) and the upregulation of KEAP1 gene. In addition, deltamethrin resulted in the activation of the IRE1 and PERK-ATF4-CHOP signaling pathways, leading to endoplasmic reticulum stress in crucian carp. According to Li et al. (2019), treatment with GBH (glyphosate-based herbicide increased the levels of HSP70, HSP90, and HSC70 in various organs of fish, suggesting a possible link between HSP induction and GBH toxicity. Further investigation showed that GBH notably increased IL-1β, IL-6, IL-8, IFN-γ, and TNF-α expression and altered the IL-10 and TGF-β levels. GBH exposure also inhibited T-AOC activity but increased the MDA level. These results suggest that GBH induces oxidative stress and immuno-toxicity in common carp (Figure 6). So, in general, several pesticides have been found to have adverse effects on the fish population and prevalent oxidative stress in them seems to be common under pesticide exposure.

The potential uses of nanotechnology in the aquaculture and fisheries sectors are numerous. Typically, a nanoparticle (NP) is defined as a structure with a size between 0.1 and 100 nm (1/1,000,000 mm). Nanoparticles have attracted much attention in diagnosing various fish diseases due to their sensitiveness and preciseness in diagnosing various bacterial, viral and fungal diseases (Munawar et al., 2021). Various kinds of nanoparticles, like ZnO, TiO₂, Cu-based nanoparticles, silver nanoparticles, etc, are used in the diagnosis of fish diseases. Ravikumar et al. (2012) reported that nanoparticles of CeO₂ could be used for control of several fish diseases associated with Vibrio parahaemolyticus, Serratia spp., Aeromonas hydrophila, Vibrio harveyi, Bacillus subtilis, and Serratia sp. Saad et al. (2022) investigated the effects of biological selenium nanoparticles on bacterial load and heavy metal accumulation in Nile tilapia fish and reported that those nanoparticles could able to reduce the load of Aeromonas hydrophila by 28%–45% and cadmium and mercury levels by 50%–87% and 57%–73%, respectively in fish organs. Chen et al. (2016) reported that nano-biosensors can detect fish contaminants and very low concentrations of pathogens such as bacteria, viruses, and parasites. They may be based on various nanomaterials, such as carbon nanotubes.

In addition to this, the microorganisms and heavy metals present in the watercourse retards the growth rate of fishes leading to a great economic loss in the fishery sector (Shah and Praveen, 2020). Nanotechnology has been used very effectively to remove toxins from water. Poor performance and harm to the organisms result from water quality loss (Boyd & Tucker, 2012). Globally, the use of nanotechnology in water treatment is on the rise, with a wide range of potential customer-specific uses. The capacity to include diverse qualities in multifunctional materials is one of the most beneficial features of these systems, including nano-adsorbents, nanometals, nanomembranes, and nano-photocatalysts, among others. For instance, nanomaterials can simultaneously remove particles and pollutants and increase process efficiency (Gehrke et al., 2015). Water treatment is one of the most crucial foundational elements needed for sustained aquaculture. The excessive use of antibiotics and other synthetic chemical substances in fisheries and the discharge of waste materials from cities, businesses, and agriculture, have made water poisoning leading to an indirect impact on aquatic individuals as well as causing foodborne illnesses when consumed by human beings. These waters contain heavy metals that cause fish to grow more slowly and eventually die. Aquaculture uses nanotechnology mostly for treating water to provide a suitable environment for fish growth and reproduction. In this light, the scientific community supports adsorption and photocatalysis as the most effective and reasonably priced methods of water purification. Activated forms of carbon or alumina, along with either zeolite or iron-containing materials can be used effectively to hold both aerobic and anaerobic biofilm to remove various pollutants like nitrates, nitrites and ammonia.

When silver nanoparticles are used to cure fungi in water directly, young trout have been found to be affected, although rainbow trout fish kept in fish farms may not become infected by fungi if their water is filtered through a device coated with silver nanoparticles. The ultrafine form of iron particles can be used as a cleaning agent for less harmful compounds present in water courses like dioxins, carbon tetrachloride, trichloroethane, or polychlorinated biphenyls (Rather et al., 2011). TiO2 has been used effectively to treat wastewater due to its non-toxicity property, biological and chemical stability and photocatalytic activities. Many previous studies have documented the photocatalytic activities of TiO2 against various disease-causing bacterial, algal, and viral agents (Ouyang et al., 2016). Kuang et al. (2017) reported that graphene oxide and graphene nanosheets can be used as efficient water source cleaning agent. The graphene oxide -TiO2 combination has been used for removing various heavy metal ions and organic dyes from polluted water (Atchudan et al., 2017). Also, silver nanoparticles are gaining much more importance in cleaning the water source that is used for fish rearing due to their advanced cleaning system (Munawar et al., 2021).

Unquestionably, nutraceuticals are recognized to be highly effective in enhancing fish development and immune characteristics. However, the costs associated with their incorporation are higher than the minimum requirements. Many studies supported the use of nanotechnology in fisheries for the efficient delivery of nutraceuticals and dietary supplements. By making nutrients more soluble and protecting those from the harsh gut environment, these systems primarily aim to increase the bioavailability, bio-accessibility, and, subsequently, effectiveness of the nutrients. Previous studies also reported a faster growth rate and higher final body weight in Carassius auratus gibelio young carp when fed with diet supplemented with iron and selenium nanoparticles (ETC, 2003; Frederick et al., 2010). Iron nanoparticles have been proven to have a growth-promoting effect on young carp and sturgeon. Additionally, it was discovered that adding nano-selenium to a fish’s diet could increase its weight, relative growth performance, antioxidant activity, glutathione peroxidase activity, and concentrations of selenium in muscle of crucian carp (C. auratus gibelio) (Bhupinder, 2014). Khosravi-Katuli et al. (2017) reported that using nanoparticles in the fisheries sector enhanced immunomodulation, digestion and reproduction compared to other forms of Se. Wang et al. (2013) also reported that nano supplementation could help in increasing fish and animal productivity by reducing oxidative stress. Previous studies reported that diets supplemented with 0.2 mg/kg selenium nanoparticles had rapid weight gain rate and a reduced feed coefficient than feed with 0, 0.1, 0.4, 0.8, and 1.6 mg/kg selenium nanoparticles (Qin et al., 2016). Feed supplemented with selenium nanoparticles increases immunity and disease resistance while providing resistance to the effects of hypoxic stress (Kumar et al., 2017).

When delivering biological materials, nanoparticles are less expensive than other materials. Additionally, nanoparticles possess adjuvant qualities that can raise antigen effectiveness. The cellular uptake of nanoparticles is facilitated by their diminutive size, as they are only capable of entering living cells via cellular endocytosis (Zhao et al., 2014). Adjuvants lessen administration frequency while enhancing immune response (Evensen, 2009). Luis et al. (2019) reported that the stability, solubility, targeting, biocompatibility, and permeability of vaccines can be enhanced by the application of nanotechnology.

In conclusion, it can be asserted that the implementation of nanotechnology in aquaculture systems, the administration of pharmaceuticals through porous nanostructures in fish feed, and the utilization of nano sensors for pathogen detection in aquaculture systems hold promising prospects for impacting fish health.