## 4 Occurrence of Micro and Nano-Plastics in Fish Gills and Consequent Effects
Moreover, the authors emphasized that the toxicity of smaller MPs was closely related to other different factors, including the target tissue, exposure duration, and MPs chemical properties. Oxidative stress induced by MPs leads to consequent gill structural damage and histological changes [127]: abscission in gill lamellae, loose arrangement of gill filaments, shortening and thickening of gill lamellae. As noticed for oxidative stress, also gene expression could be affected by MPs and NPs exposure in different ways based on the plastic sizes. [PERSON] et al. [31] found the smallest MPs particles, used in their study, induced fifty gene up-regulation in _Oncorhynchus mykiss_, S100a gene up-regulation in zebrafish gills and up-regulation of three immune genes in zebrafish gills (ifny, il1\(\beta\), and sigm). So, the scientists speculated that immune gene expression starts in gill epithelia and associated cells after small microplastics are taken up by them. For [PERSON] et al. [135], another effect of PSMPs exposure was a weakened Na+/K+-ATPase activity in gills that could affect the osmotic balance of these organs. Besides the above-mentioned damages on the gills, a changed oxygen consumption that is an indicator of respiration stress, can occur. Therefore, bigger microplastics have a greater impact than smaller ones, as [PERSON] et al. [139] demonstrated. On the other hand, [PERSON] et al. [134] argue that nanoplastics are more dangerous for gills than microplastics. According to these authors, NPs effects on histological damage have an entity that is proportional to the exposure concentration. Interestingly, the authors found that, by detecting gill at both microscopic and ultra-micro levels, no enrichment of MPs or NPs was found within their tissues. Despite this, the gill tissues of larvae showed damage phenomenon. Differently from what reported above, some authors found no damage or alteration on gills after MPs and NPs exposure [133; 137]. The inconsistencies in previous studies may be due to the different experimental concentrations employed (Table 2). In addition to MPs and NPs effects on gills, there are other issues. One of the concerns about MPs and NPs is represented by the evidence that, once absorbed by the gill, they can be internalized and spread in fish body [43; 141]. Another growing concern is represented by the effects of the co-exposure to microplastics with other contaminants. This is due to the evidence that MPs and NPs, not only can increase the bioavailability and uptake of contaminants but can also enhance their toxic effect on gills [46; 142; 143; 144]. For example, [PERSON] and his team [145], demonstrated that low-density polyethylene (LDPE) fragments can cause toxicity and modulate the adverse impacts of phenanthrene (Phe), by influencing among other parameters, the degree of tissue changes (DTC) in the gills. In the gill tissues, histological alterations were observed, e.g., some basal cell hyperplasia, sloughing, necrosis in the connective tissue. By increasing the concentration of MPs, the following phenomena were observed: epithelial lifting, hyperplasia, necrosis of the connective tissue, extensive cell sloughing, desquamation and consequently blood vessel exposure and, in some instances, total loss of the secondary lamellae. This corroborates the concentration-dependent impact of MPs that other scientists [46; 136] encountered too. Besides the oxidative stress induction, microplastics associated with other substances can enhance the expression of immune-related genes in gills as shown by [PERSON] et al. [144] with phenanthrene on zebrafish. Toxicity of Microl plastics and Nanoplastics in Digestive Tract: Intestinal Retention Time, Uptake and Elimination  
The food-borne route is the major contamination by MP/NPs pathway, with the gut being the target organ [146]. Plastic fragments, in the form of microfibers or microbeads, may accumulate in digestive tract of fish via food and water [147,148].