A critical review on male-female reproductive and developmental toxicity induced by micro-plastics and nano-plastics through different signaling pathways.

It is widely accepted that humans are constantly exposed to micro-plastics and nano-plastics through various routes, including inhalation of airborne particles, exposure to dust, and consumption of food and water. It is estimated that humans may consume thousand to millions of micro-plastic particles, equating to several milligrams per day. Prolonged exposure to micro-plastics and nano-plastics has been linked to negative effects on different living organisms, including neurotoxicity, gastrointestinal toxicity, nephrotoxicity, and hepatotoxicity, and developmental toxicities. The main purpose of this review is to explore the effect of micro-plastics and nano-plastics on the male and female reproductive system, as well as their offspring, and the associated mechanism implicated in the reproductive and developmental toxicities. Micro-plastics and nano-plastics have been shown to exert negative effects on the reproductive system of both male and female mammals and aquatic animals, including developmental impacts on gonads, gametes, embryo, and their subsequent generation. In addition, micro-plastics and nano-plastics impact the hypothalamic-pituitary axes, leading to oxidative stress, reproductive toxicity, neurotoxicity, cytotoxicity, developmental abnormalities, poor sperm quality, diminishes ovarian ovulation and immune toxicity. This study discusses the so many different signaling pathways associated in the male and female reproductive and developmental toxicity induced by micro-plastics and nano-plastics.

Nutraceutical Effect of Resveratrol on the Mammary Gland: Focusing on the NF-κb /Nrf2 Signaling Pathways.

The aim of this study is to evaluate the defensive role of resveratrol, which is antagonistic to the oxidative stress and inflammation that is prompted by LPS in mammary tissue of female mice. Thirty adult mice were distributed into three groups (n = 10) control (CON), lipopolysaccharides at 2.5 mg/kg (LPS), and lipopolysaccharides at 2.5 mg/kg with 2 mg/kg of resveratrol (RES + LPS). The treatments were applied for 15 consecutive days. Spectrophotometry was used to quantify ROS in the blood, and proinflammatory cytokines concentrations were determined through radioimmunoassay. NF-κB, Jnk, IL-1ß, Erk, IL-6, Nrf2 and TNF-α were quantified by RT-qPCR, and Western blots were used to quantifyP65 and pP65 protein intensities. MDA production was considerably increased, and the activity of T-AOC declined in the LPS treatment in comparison with the CON group but was significantly reversed in the RES + LPS group. Proinflammatory cytokines production and the genes responsible for inflammation and oxidative stress also showed higher mRNA and pP65 protein intensity in the LPS group, while Nrf2 showed a remarkable decline in mRNA expression in the LPS versus the CON group. All these mRNA intensities were reversed in the RES + LPS group. There were no remarkable changes in P65 protein intensity observed between the CON, LPS, and RES + LPS groups. In conclusion, resveratrol acts as a protective agent to modulate cellular inflammation and oxidative stress caused by LPS in mammary tissue of female mice.

Long-term high-concentrate diet feeding induces apoptosis of rumen epithelial cells and inflammation of rumen epithelium in dairy cows.

The aim of the present study was to evaluate how long-term high-concentrate diet feeding affected rumen epithelium (RE) of dairy cows. So, 12 mid-lactating multiparous cows were divided into two groups randomly fed either with high-concentrate diet (HC, concentrate: forage = 6: 4) or low-concentrate diet (LC, concentrate: forage = 4:6) for 20 weeks. Remarkable upregulation of lipopolysaccharide (LPS) level and depress of pH in rumen fluid were induced by HC compared with LC group. mRNA abundance of interleukin-6 (IL-6), interleukin-8 (IL-8), C-C motif chemokine ligand 5 (CCL5), caspase-3, caspase-8, and caspase-9 were elevated in RE of HC group compared with LC group. Greater protein abundance of phosphorylated NF-κB p65, IL-6, and tumor necrosis factor α (TNF-α) was observed in RE of cows fed HC than that fed LC. Abundance of protein related to proapoptotic response (cytochrome c, BAX and caspase-3) in HC group was greater than that in LC group, while the abundance of anti-apoptotic factor protein (Bcl-2) was lower in HC group than LC group. Therefore, the present study demonstrated that long-term high-concentrate diet feeding upregulated LPS level in rumen fluid and induced the proinflammatory response in the rumen epithelium and apoptosis of rumen epithelial cells.

Efficacy of sodium butyrate in alleviating mammary oxidative stress induced by sub-acute ruminal acidosis in lactating goats.

Sub-acute ruminal acidosis (SARA) [1] is one of the most common problems of dairy animals causing great economical loss due to decreased milk production. Here we determined the antioxidant effect of sodium butyrate (NaB) [2] in experimentally induced SARA and its effects on mammary epithelial tissues of goat. Goats (n = 12) were equally divided into two groups: high-concentrate (HC) as control group fed with HC diet (concentrate: forage = 6:4) whereas HC + NaB as treatment group fed HC diet with NaB at 1% by weight for 24 weeks. Mammary epithelial tissue samples were analyzed for the expression of genes and proteins responsible for oxidative stress as well as biochemical markers of antioxidant activity in the form of Reactive Oxygen Species (ROS). The total antioxidant capacity (T-AOC) of antioxidant enzymes was also calculated. Butyrate induced antioxidant effect by increasing mRNA and protein abundance of antioxidants in mammary gland of HC + NaB group compared to HC group. Likewise, the total antioxidant capacity (T-AOC) was significantly increased and Malondialdehyde (MDA) concentration was decreased in HC + NaB group compared to HC group. It is concluded that oxidative stress in mammary gland of goats induced by high concentrate diet was alleviated by NaB supplementation.

Sodium butyrate suppresses NOD1-mediated inflammatory molecules expressed in bovine hepatocytes during iE-DAP and LPS treatment.

Nucleotide oligomerization domain protein-1 (NOD1), a cytosolic pattern recognition receptor for the γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) is associated with the inflammatory diseases. Very little is known how bovine hepatocytes respond to specific ligands of NOD1 and sodium butyrate (SB). Therefore, the aim of our study was to investigate the role of bovine hepatocytes in NOD1-mediated inflammation during iE-DAP or LPS treatment or SB pretreatment. To achieve this aim, hepatocytes separated from cows at ∼160 days in milk (DIM) were divided into six groups: The nontreated control group (CON), the iE-DAP-treated group (DAP), the lipopolysaccharide-treated group (LPS), iE-DAP with SB group (DSB), LPS with SB group (LSB), and the SB group. Both iE-DAP and LPS highly increased the expression of both NOD1 and RIPK2, the two key factors for the immune response in hepatocytes. IκBα, NF-κB/p65, and MAP kinases (ERK, JNK, and p38) were activated through phosphorylation. The activation of NF-κB and MAPK pathway consequently increased the proinflammatory cytokines, IL-6, TNF-α, IL-8, and IFN-γ and the chemokines CCL5, CCL20, and CXCL-10. Both treatments improved iNOS/NOS2 expression. However, iE-DAP was failed to express acute phase protein SAA3, but HP and LPS HP but SAA3. These ligands also increased LRRK2, TAK1, TAB1, and ß-defensins expression. The SB pretreatment at lower dose restored the function of hepatocytes by suppressing these increased molecules, as HDAC3 was inhibited. The activated NOD1 negatively regulated the expression of FOXA2. Altogether these data suggest an important role of bovine hepatocytes to promote immune responses via NOD1 expression during infection in the liver and a key role of SB to attenuate inflammation.

Lipopolysaccharide induces oxidative stress by triggering MAPK and Nrf2 signalling pathways in mammary glands of dairy cows fed a high-concentrate diet.

The goal of current investigations was to reveal the molecular mechanism triggered through feeding a diet with high-concentrate to dairy cows for subacute ruminal acidosis (SARA) induction and to examine the oxidative stress parameters in their mammary epithelial tissue. In an eighteen-weeks feeding trial, 12 Holstein Friesian cows with a standard weight of 455 ±â€¯28 kg were evenly divided into two groups and given either a low-concentrate (LC, forage to concentrate ratio = 6:4) or a high-concentrate (HC, forage to concentrate ratio = 4:6) diet. A remarkable reduction in ruminal pH also increased ruminal lipopolysaccharide (LPS) concentration that was observed in the high-concentrate group of cows at 4 h post-feeding in the morning. Moreover, reduced milk yield was observed in the HC group. The relative mRNA abundance of glutathione peroxidase (GPX) 1 and 3 and superoxide dismutase (SOD) 1 and 2 were down-regulated in high-concentrate fed animals than in the LC, while mRNA was expressed with no change in the of SOD3 among groups. In addition, genes responsible for oxidative stress e.g., ERK, JNK, and p38 were also showed dramatically high mRNA intensity in HC group. The protein concentration of ERK, pERK, pJNK, with pp38, were up-regulated significantly as JNK & p38 showed no big difference. While Nrf2 and pNrf2 were down-regulated considerably in HC group. The total antioxidant capacity (T-AOC) was significantly decreased but of Malondialdehyde (MDA) concentration was raised in HC group than in LC. We thus proposed that higher levels of endogenous LPS may affect the Mitogen-activated protein kinases (MAPK) and nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent antioxidant response.

NOD1/NF-κB signaling pathway inhibited by sodium butyrate in the mammary gland of lactating goats during sub-acute ruminal acidosis.

Animals nurtured with a high-concentrate diet for a more extended period can cause subacute ruminal acidosis (SARA). In this study, twelve mid-lactating goats were separated into two groups (n = 6): a high concentrate diet (HC) control and a high concentrate with buffer (HCB) treatment group. Rumen fistula was installed in all lactating goats in the 14th week of the experiment. Goats were slaughtered in the 24th week. Our results showed that a pH value < 5.8 sustained at different periods of time for more than 3 h/day in the group HC, which confirms that SARA was prompted efficiently. Additionally, the group HCB exhibited lower concentration of LPS in peripheral blood than the group HC. Radioimmunoassay revealed a substantial reduction in the concentration level of proinflammatory cytokines in the lacteal blood of the group HCB compared to group HC. The transcriptional profiles in mammary gland following different treatments showed a significant decrease in the expression of NOD1, IKß, and NF-κB in HCB group, followed by a decreased transcriptional level of (TNF-α, IL-1ß and IL-6). Our research explores that HC diet nurtured to lactating goats for a more extended period can induce SARA by increasing the LPS and proinflammatory cytokine concentrations in plasma, that ultimately triggers the NOD1/NF-κB inflammatory pathway and induce mammary cell inflammation. Additionally, oral supplementation of sodium butyrate can decrease the concentrations of LPS and proinflammatory cytokines and inhibits NOD1/NF-κB inflammatory pathway.

Sodium Butyrate Ameliorates High-Concentrate Diet-Induced Inflammation in the Rumen Epithelium of Dairy Goats.

To investigate the effect of sodium butyrate on high-concentrate diet-induced local inflammation of the rumen epithelium, 18 midlactating dairy goats were randomly assigned to 3 groups: a low-concentrate diet group as the control (concentrate:forage = 4:6), a high-concentrate (HC) diet group (concentrate:forage = 6:4), and a sodium butyrate (SB) group (concentrate:forage = 6:4, with 1% SB by weight). The results showed that, with the addition of sodium butyrate, the concentration of lipopolysaccharide (LPS) in rumen fluid (2.62 × 104 ± 2.90 × 103 EU/mL) was significantly lower than that in the HC group (4.03 × 104 ± 2.77 × 103 EU/mL). The protein abundance of pp65, gene expression of proinflammatory cytokines, and activity of myeloperoxidase (MPO) and matrix metalloproteinase (MMP)-2,9 in the rumen epithelium were significantly down-regulated by SB compared with those in the HC group. With sodium butyrate administration, the concentration of NH3-N (19.2 ± 0.890 mM) in the rumen fluid was significantly higher than that for the HC group (12.7 ± 1.38 mM). Severe disruption of the rumen epithelium induced by HC was also ameliorated by dietary SB. Therefore, local inflammation and disruption of the rumen epithelium induced by HC were alleviated with SB administration.