*5.3. Pigs*

ZnO and Cu salts, traditionally used in high doses as supplements to piglet's diet, stimulate piglet's daily gain and decrease feed conversion factor. However, the application of high concentrations of these metal additives could result in increased environmental pollution of soil and tap water; on the other hand, Zn applied at doses 2500–3000 mg/kg feed can contribute to the development of antimicrobial resistance and may regulate the expression of genes that modify piglets' immune response. Consequently, higher bioavailability which could be achieved by applying nanosized ZnO/Cu particles could notably reduce the dietary inclusion rate and environmental pollution with preserving beneficial impact on pig's health [244].

The degree of the reduction of piglet diarrhea incidence observed with a low dose of ZnO NPs (600 mg Zn/kg) supplemented to the basal diet of weaning piglets was comparable with that observed with the dose of 2000 mg Zn/kg when bulk ZnO was used, which could be connected with improved intestinal microbiota and inflammation response in piglets at the ZnO NPs application. Moreover, the application of ZnO NPs could contribute to reduced Zn environmental pollution [284]. ZnO NPs used as a DIS increased Zn digestibility, serum GH levels, and carbonic anhydrase activity and enhanced the immune response of weanling piglets [285].

Cr(III) belongs to essential elements in the nutrition of both animals and humans, and in many animal species its deficiency results in reduced feed intake, lower weight gains, reproductive disorders, and increased lipid levels, and a moderate Cr deficiency represents a risk factor of ischemic heart disease with myocardial infarction and coronary artery disease. Cr improves lean body mass in animals, increases growth rate and feed conversion, and improves feed intake and energy efficiency, and the dietary Cr requirement of an animal body is probably 300 μg Cr/kg d.w. of feed. A pronouncedly increased Cr content in the blood, longissimus muscle, heart, liver, kidneys, jejunum, and ileum was observed in pigs receiving dietary Cr nanocomposite supplementation [286]. Dietary CrPic NPs supplementation at 400 ppb increased feed intake in finisher gilts during mid-summer and was able to improve some of the adverse effects of heat stress in pigs, through decreasing circulating cortisol levels [287]. Pigs with initial body weight of 66.10 ± 1.01 kg receiving basal diet supplemented with 200 or 400 μg/kg of Cr from Cr-loaded CS NPs (Cr–CS NPs) for 35 d showed increased carcass lean ratio and longissimus muscle area, decreased carcass fat ratio and backfat thickness as well as increased serum free fatty acids, lipase activity, and serum insulin-like growth factor I, while a decreased level of serum insulin was estimated. Moreover, decreased activities of fatty acid synthase and malate dehydrogenase and increased activity of hormone-sensitive lipase in subcutaneous adipose tissue were observed in treated pigs. These results indicate a favorable impact of Cr in the form of the Cr–CS NPs on growth, carcass characteristics, pork quality, and lipid catabolism in finishing pigs [288]. The control diet supplemented with 200 μg Cr from Cr nanocomposite pronouncedly reduced serum levels of glucose, urea nitrogen, triglyceride, cholesterol, and nonesterified fatty acid, increased total protein, HDL, and lipase activity in finishing pigs with initial weight 64.8 ± 0.83 kg fed for 35 d, and considerably increased serum insulin-like growth factor I, while reducing serum insulin and cortisol levels. Moreover, it affected immune status in finishing pigs, which was reflected in notable increments of IgM and IgG contents in plasma [289].

## *5.4. Other Pets*

Dried matrices of CS Cu chelate gels designed as a multimicronutrient feed additive for cattle were loaded with vitamin riboflavin. Following restricted rehydration in simulated rumen fluid, they exhibited sustained release of riboflavin without releasing Cu in these neutral conditions for up to 24 h, demonstrating Cu rumen bypass. A sustained release of the mineral was observed in abomasal conditions of pH 2 over a 3 h period suggesting that this formulation could supply nutritionally relevant levels of the free mineral in these conditions, as required for effective supplementation in cattle [290].

A decreasing trend in serum Fe concentration was observed in Lori-Bakhtiary sheep, which orally received SeNPs and Na2SO3 (1 mg/kg) for 10 consecutive days, particularly during the early and middle stages of supplementation (0–20 days) in contrast to the increasing levels of total iron binding capacity, suggesting that the expression of transferrin and its receptor genes was considerably increased. However, after this period, the expression of the transferrin and transferrin binding receptor genes showed a notable decrease, especially in SeO3 2− treated animals [291].

Improved rumen fermentation and feed utilization, stimulation of rumen microbial activity, digestive microorganisms, and enzyme activity by supplementation of SeNPs in basal diet of sheep with optimum dose approx. 3.0 g/kg dietary dry mater was reported by Shi et al. [292]. Using the rumen simulation technique, it was observed that nanoemulsified soyabean oil modulated the PUFAs proportions in ruminal cultures, which was reflected in markedly increased proportions of oleic acid, α-LLA, and α-LNA in the fermentation fluid without any negative effect on rumen fermentation parameters [293].

Nano-copper as a new growth promoter in the diet of growing New Zealand white rabbits was reported by Refaie et al. [294]. Similarly, the male five-week-old New Zealand white rabbits fed with the basal diet supplemented with 60 and 30 mg ZnO NPs /kg diet had higher body weight, daily weight gain, daily feed intake, serum total protein, globulin, IgG, and SOD compared to control animals and rabbits fed with a diet supplemented with bulk ZnO (60 mg/kg diet), suggesting that traditional zinc sources in rabbit diets could be replaced by 30 mg ZnO NP/kg diet [295]. On the other hand, Ismail and El-Araby [296] recommended the combined use of bulk and nanosized ZnO at ratio 1:1 in the dietary system of rabbit's farms ensuring dietary supplementation with Zn as an essential element but reducing adverse effects such as lipid peroxidation and oxidant stress induced by the whole dose of ZnO NPs. A complete overview of the used nanoscale veterinary dietary supplements is shown in Figure 3.

**Figure 3.** Summary of most frequently used veterinary dietary nanosupplements.
