Zinc oxide is an essential ingredient of many enzymes, sun screens, and ointments for pain and itch relief. Its microcrystals are very efficient light absorbers in the UVA and UVB region of spectra due to wide bandgap. Impact of zinc oxide on biological functions depends on its morphology, particle size, exposure time, concentration, pH, and biocompatibility. They are more effective against microorganisms such as Bacillus subtilis, Bacillus megaterium, Staphylococcus aureus, Sarcina lutea, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Pseudomonas vulgaris, Candida albicans, and Aspergillus niger. Mechanism of action has been ascribed to the activation of zinc oxide nanoparticles by light, which penetrate the bacterial cell wall via diffusion. It has been confirmed from SEM and TEM images of the bacterial cells that zinc oxide nanoparticles disintegrate the cell membrane and accumulate in the cytoplasm where they interact with biomolecules causing cell apoptosis leading to cell death.

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Properties of Zinc Oxide Nanoparticles and Their Activity Against Microbes

The main molecular mechanisms explaining the well-established antioxidant and reducing activity of N-acetylcysteine (NAC), the N-acetyl derivative of the natural amino acid l-cysteine, are summarised and critically reviewed. The antioxidant effect is due to the ability of NAC to act as a reduced glutathione (GSH) precursor; GSH is a well-known direct antioxidant and a substrate of several antioxidant enzymes. Moreover, in some conditions where a significant depletion of endogenous Cys and GSH occurs, NAC can act as a direct antioxidant for some oxidant species such as NO2 and HOX. The antioxidant activity of NAC could also be due to its effect in breaking thiolated proteins, thus releasing free thiols as well as reduced proteins, which in some cases, such as for mercaptoalbumin, have important direct antioxidant activity. As well as being involved in the antioxidant mechanism, the disulphide breaking activity of NAC also explains its mucolytic activity which is due to its effect in reducing heavily cross-linked mucus glycoproteins. Chemical features explaining the efficient disulphide breaking activity of NAC are also explained.

N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why

In recent years, zinc oxide nanoparticles (ZnO NPs) have gained tremendous attention attributed to their unique properties. Notably, evidence has shown that zinc is an important nutrient in living organisms. As such, both prokaryotes and eukaryotes including bacteria, fungi and yeast are exploited for the synthesis of ZnO NPs by using microbial cells or enzyme, protein and other biomolecules compounds in either an intracellular or extracellular route. ZnO NPs exhibit antimicrobial properties, however, the properties of nanoparticles (NPs) are depended upon on their size and shape, which make them specific for various applications. Nevertheless, the desired size and shape of NPs can be obtained through the optimization process of microbes mediated synthesis by manipulating their reaction conditions. It should be noted that ZnO NPs are synthesized by various chemical and physical methods. Nonetheless, these methods are expensive and not environmentally friendly. On that account, the microbes mediated synthesis of ZnO NPs have rapidly evolved recently where the microbes are cleaner, eco-friendly, non-toxic and biocompatible as the alternatives to chemical and physical practices. Moreover, zinc in the form of NPs is more effective than their bulk counterparts and thus, they have been explored for many potential applications including in animals industry. Notably, with the advent of multi-drug resistant strains, ZnO NPs have emerged as the potential antimicrobial agents. This is mainly due to their superior properties in combating a broad spectrum of pathogens. Moreover, zinc is known as an essential trace element for most of the biological function in the animal’s body. As such, the applications of ZnO NPs have been reported to significantly enhance the health and production of the farm animals. Thus, this paper reviews the biological synthesis of ZnO NPs by the microbes, the mechanisms of the biological synthesis, parameters for the optimization process and their potential application as an antimicrobial agent and feed supplement in the animal industry as well as their toxicological hazards on animals.

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Microbial synthesis of zinc oxide nanoparticles and their potential application as an antimicrobial agent and a feed supplement in animal industry: a review

Zinc-oxide nanoparticles are being used in a wide range of commercial applications and are therefore expected to find their way into the soil ecosystem. Problems concerning Zinc-oxide nanoparticle toxicity, in-vitro and in-vivo testing methods for living organisms, the development of environmental health criteria and the acceptance of toxicity limits of metal nanoparticles, are topical. This review will contribute to understanding the fate and behaviour of Zinc-oxide nanoparticles in soil, their uptake and distribution within plants, animals, and microbes as well as their interactions with other pollutants. It is an essential prerequisite to environmentally realistic studies of the ecotoxicology of nanoparticles. Increased application of nanoparticles threatens communities as well as plants, terrestrial and aquatic animals. Thus, it is important to explore whether nanoparticles could compromise soil biodiversity and the important functions maintained by soil communities.

Effects of zinc-oxide nanoparticles on soil, plants, animals and soil organisms: A review

Oxidative stress is implicated in a wide range of intestinal disorders and closely associated with their pathological processes. Resveratrol (RSV), a plant extract, plays a vital role in protecting various organs in vitro and in vivo. However, the benefits of RSV are controversial, and underlying mechanisms for its antioxidant effects on intestinal epithelial cells remain unclear. In this study, we evaluated the effects of RSV on oxidative stress induced by H2O2 in IPEC-J2 cells. We found that pretreatment with RSV significantly increased cell viability; increased expression levels of tight junction (TJ) proteins (claudin-1, occludin, and ZO-1); improved activities of superoxide dismutase-1 (SOD-1), catalase (CAT), and glutathione peroxidase (GSH-Px); and decreased intracellular reactive oxygen species (ROS) levels and apoptosis induced by H2O2 ( ). In addition, RSV upregulated Akt phosphorylation, Nrf2 phosphorylation, and expression levels of antioxidant genes HO-1, SOD-1, and CAT in a dose-dependent manner ( ) under oxidative stress. Knockdown of Nrf2 by short-hairpin RNA (shRNA) abrogated RSV-mediated protection against H2O2-induced apoptosis, RSV-induced increase of TJ protein levels, and antioxidant gene expression (SOD-1, CAT, and GSH-Px) ( ). Consistent with Nrf2 knockdown, the PI3K/Akt inhibitor LY294002 significantly suppressed RSV-induced Nrf2 phosphorylation and RSV-induced increase of TJ protein levels and antioxidant gene expression under H2O2 treatment ( ). Collectively, these results demonstrate that RSV can directly protect IPEC-J2 cells against oxidative stress through the PI3K/Akt-mediated Nrf2 signaling pathway, suggesting that RSV may be an effective feed additive against intestinal damage in livestock production.

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Resveratrol Attenuates Oxidative Stress-Induced Intestinal Barrier Injury through PI3K/Akt-Mediated Nrf2 Signaling Pathway

Zinc oxide nanoparticles (nano-ZnOs) are widely used and possess great potentials in agriculture and biomedicine. It is inevitable for human exposure to these nanoparticles. However, no study had been conducted to investigate the long term effects of nano-ZnOs. This study aimed at investigating effects of nano-ZnOs on development, zinc metabolism and biodistribution of minerals (Zn, Fe, Cu, and Mn) in mice from week 3 to 35. After the characteristics of nano-ZnOs were determined, they were added into the basal diet at 0, 50, 500 and 5000 mg/kg. Results indicated that added 50 and 500 mg/kg nano-ZnOs showed minimal toxicity. However, 5000 mg/kg nano-ZnOs significantly decreased body weight (from week 4 to 16) and increased the relative weights of the pancreas, brain and lung. Added 5000 mg/kg nano-ZnOs significantly increased the serum glutamic-pyruvic transaminase activity and zinc content, and significantly enhanced mRNA expression of zinc metabolism-related genes, including metallothionein 1(32.66 folds), metallothionein 2 (31.42 folds), ZIP8 (2.21folds), ZIP14 (2.45 folds), ZnT1 (4.76 folds), ZnT2 (6.19 folds) and ZnT4 (1.82 folds). The biodistribution determination showed that there was a significant accumulation of zinc in the liver, pancreas, kidney, and bones (tibia and fibula) after receiving 5000 mg/kg nano-ZnO diet, while no significant effects on Cu, Fe, and Mn levels, except for liver Fe content and pancreas Mn level. Our results demonstrated that long term exposure to 50 and 500 mg/kg nano-ZnO diets showed minimal toxicity. However, high dose of nano-ZnOs (5000 mg/kg) caused toxicity on development, and altered the zinc metabolism and biodistribution in mice.

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Effects of Long-Term Exposure to Zinc Oxide Nanoparticles on Development, Zinc Metabolism and Biodistribution of Minerals (Zn, Fe, Cu, Mn) in Mice.

The toxicological effects of zinc oxide nanoparticles (nano-ZnOs) are related to their dissolution and interference with zinc ion homeostasis. High-soluble zinc sources may produce more severe and acute toxicity; however, the evaluation of potential toxicity of long-term exposure to nano-ZnOs and high-soluble sources of zinc remains obscure. This study aimed at evaluating effects of nano-ZnOs and zinc sulfate on development, serum and hematological parameters, and mineral concentrations in selected tissues and intestinal microbiota in mice via gastrointestinal administration for 7 weeks. Results indicated that 250 mg/kg nano-ZnOs reduced the body weight from weeks 8 to 11, increased serum glutamic-pyruvic transaminase activity, and increased the zinc concentrations of the serum, liver, and kidney while did not affect the relative organ weight, intestinal microbiota, and other mineral concentrations (Fe, Cu, and Mn) in the kidney, liver, and thigh muscle. Oral administration with 250 mg/kg zinc sulfate seemed to show more severe and acute toxicity since mice in zinc sulfate group exhibited reduced body weight from weeks 5 to 11, decreased relative pancreas weight, and increased serum glutamic-oxalacetic transaminase activity and intestinal enteric group.

Evaluation of Long-Term Toxicity of Oral Zinc Oxide Nanoparticles and Zinc Sulfate in Mice.

cope
Emerging evidence has identified mitochondrial biogenesis and oxidative phosphorylation as potential targets for the prevention and treatment of metabolic syndrome. This study investigated the effect of resveratrol (RSV) on hepatic mitochondrial function in intrauterine growth-retarded (IUGR) suckling piglets.

Methods and results
Seven normal birth weight (NBW) and fourteen IUGR neonatal male piglets were selected. Piglets were fed control diets supplemented with 0 (NBW-CON), 0 (IUGR-CON), and 1.0 (IUGR-RSV) g RSV per kg of milk dry matter from 7 to 21 days of age (n = 7), respectively. Mitochondrial function, swelling, and redox status in the liver were assessed. Compared with NBW, IUGR impaired hepatic mitochondrial biogenesis and energy homeostasis of the control piglets. IUGR control piglets showed overproduction of superoxide radicals, increased concentration of malondialdehyde, and marked swelling in the mitochondria. RSV improved mitochondrial DNA content, ATP production, and fatty acid oxidation in the liver of IUGR piglets, along with an increased activity of sirtuin 1. RSV inhibited mitochondrial superoxide anion accumulation, increased complex III and manganese superoxide dismutase activities, and ameliorated mitochondrial swelling and lipid peroxidation in the IUGR piglets.

Conclusion
RSV may have beneficial effects in improving hepatic mitochondrial function and redox status in the IUGR piglets.

Resveratrol attenuates mitochondrial dysfunction in the liver of intrauterine growth retarded suckling piglets by improving mitochondrial biogenesis and redox status.

This study was conducted to investigate effects of dietary zinc oxide nanoparticles (nano-ZnOs) on growth, diarrhea rate, mineral deposition (Zn, Fe, and Mn), intestinal morphology, and barrier of weaned piglets. A total of 384 weaned piglets (Duroc × Landrace × Yorkshire) in 4 groups were fed a basal diet supplemented with 0, 400, and 800 mg/kg nano-ZnOs or 3000 mg/kg ZnO for 14 days. Compared with the control group, 800 mg/kg nano-ZnOs and 3000 mg/kg ZnO significantly increased average daily gain and decreased diarrhea rate of weaned piglets. There was no significant difference among ZnO and nano-ZnO groups. ZnO and nano-ZnOs did not affect serum activities of glutamic oxalacetic transaminase, glutamic-pyruvic transaminase, and lactate dehydrogenase. However, ZnO and 800 mg/kg nano-ZnOs significantly increased zinc concentrations in plasma, liver, pancreas, and tibia, without affecting Fe and Mn concentrations. Compared with the control group, 800 mg/kg nano-ZnOs significantly reduced plasma diamine oxidase activity, decreased total aerobic bacterial population in mesenteric lymph node, enhanced mRNA expressions of occludin, ZO-1, IL-1β, IL-10, TNF-α, and ki67 in ileal mucosa, and increased villous height, width, crypt depth, and surface area. Compared to ZnO group, 800 mg/kg nano-ZnOs significantly decreased aerobic bacterial population, enhanced mRNA expressions of occludin, IL-1β, IL-10, and TNF-α, and reduced fecal zinc concentration. These results indicated that 800 mg/kg nano-ZnOs might be a potential substitute for 3000 mg/kg ZnO in diets of weaned piglets.

Effects of Dietary Zinc Oxide Nanoparticles on Growth, Diarrhea, Mineral Deposition, Intestinal Morphology, and Barrier of Weaned Piglets

The present study investigated whether dietary methionine supplementation might protect against intrauterine growth retardation (IUGR)-induced damage in the intestine of piglets Thirty normal birth weight (NBW) female piglets and sixty same-sex IUGR piglets were weaned at 21 days of postnatal age and fed the control diet (40 g methionine per kg of feed, NBW-CON, and IUGR-CON groups) or the methionine-supplemented diet (52 g methionine per kg of feed, IUGR-MET group) for 28 days (n = 6) Piglets in the IUGR-CON group showed decreased average daily feed intake and average daily gain and an increased feed conversion ratio than those in the NBW-CON group Compared with NBW-CON piglets, IUGR-CON piglets had decreased villus height (VH) and villus height-to-crypt depth ratio in both the jejunum and ileum In addition, in comparison with the NBW-CON piglets, IUGR increased the concentration of malondialdehyde (MDA) and the index of apoptosis, while it decreased the concentrations of methionine and reduced glutathione (GSH), the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG), and the protein expression of occludin (OCLN) in both the jejunum and ileum Dietary methionine supplementation decreased the MDA and protein carbonyl concentrations and the apoptotic index, while it increased the VH level, methionine and GSH concentrations, GSH/GSSG ratio, and the OCLN protein expression in the jejunum of IUGR-MET piglets Methionine may have beneficial effects in improving intestinal integrity and oxidative status in IUGR weanling piglets

Le Zhou

Papers

Effects of Long-Term Exposure to Zinc Oxide Nanoparticles on Development, Zinc Metabolism and Biodistribution of Minerals (Zn, Fe, Cu, Mn) in Mice.

Evaluation of Long-Term Toxicity of Oral Zinc Oxide Nanoparticles and Zinc Sulfate in Mice.

Resveratrol attenuates mitochondrial dysfunction in the liver of intrauterine growth retarded suckling piglets by improving mitochondrial biogenesis and redox status.

Effects of Dietary Zinc Oxide Nanoparticles on Growth, Diarrhea, Mineral Deposition, Intestinal Morphology, and Barrier of Weaned Piglets

Effects of dietary l-methionine supplementation on intestinal integrity and oxidative status in intrauterine growth-retarded weanling piglets