Copper nanoparticles lead to reproductive dysfunction by affecting key enzymes of ovarian hormone synthesis and metabolism in female rats.

Studies on the general toxicity of copper nanoparticles (Cu NPs) have been conducted extensively, but their effects on reproductive toxicity remain unclear. In this study, we evaluated the toxic effect of Cu NPs on pregnant rats and their litter. The comparative in vivo toxicity of Cu ions, Cu NPs, and Cu microparticles (MPs) was studied in a 17-day repeated oral-dose experiment at the doses of 60, 120, and 180 mg/kg/day in pregnant rats. The pregnancy rate, mean live litter size, and number of dams decreased when exposed to Cu NPs. Moreover, Cu NPs caused a dose-dependent increase in ovarian Cu levels. The metabolomics results showed that Cu NPs caused reproductive dysfunction by altering sex hormones. In addition, in vivo and in vitro experiments showed that the ovarian cytochrome P450 enzymes (CYP450), responsible for hormone production, were significantly upregulated, whereas the enzymes responsible for hormone metabolism were significantly inhibited, resulting in a metabolic imbalance in some ovarian hormones. Furthermore, the results revealed that the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways significantly participated in the regulation of ovarian CYP enzyme expression. Overall, the results of the in vivo and in vitro toxicity experiments with Cu ions, Cu NPs, and Cu MPs suggested that toxicity from nanoscale Cu particles poses a more serious reproductive threat than microscale Cu as Cu NPs could directly damage the ovary and affect the metabolism of ovarian hormones.

Macleaya cordata extract modulates inflammation via inhibition of the NF-κB and MAPK signaling pathways in porcine alveolar macrophages induced by Glaesserella parasuis.

Glässer's disease in pigs is associated with infection by Glaesserella parasuis and is characterized by pneumonia-like symptoms, fibrinous polyserositis, polyarthritis, and meningitis. Macleaya cordata, a commonly used traditional Chinese medication, has been shown to have anti-inflammatory, antiviral, antioxidative, antimicrobial, insecticidal, and antitumor properties. However, the anti-inflammatory effects of M. cordata on G. parasuis stimulation are still poorly understood. This study explored the anti-inflammatory effects and mechanisms of M. cordata extract on G. parasuis-induced inflammatory responses, via the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, in porcine alveolar macrophages (PAMs). Porcine alveolar macrophages, when stimulated with G. parasuis, initiated transcription of interleukin (IL)-1α, IL-1ß, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α). Furthermore, p65, IκBα, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) phosphorylation were upregulated via the NF-κB and MAPK signaling pathways. However, treatment with M. cordata extract inhibited transcription of IL-1α, IL-1ß, IL-6, IL-8, and TNF-α and reduced p65, IκBα, p38, ERK, and JNK phosphorylation, by inhibiting activation of the NF-κB and MAPK signaling pathways in PAMs induced by G. parasuis. These findings reveal that M. cordata extract can reverse the inflammatory effect initiated by G. parasuis in vitro and that it possesses significant immunosuppression activity; thus, it may offer a novel strategy for controlling and treating G. parasuis infection.

La maladie de Glässer chez les porcs est associée avec une infection par Glaesserella parasuis et est caractérisée par des symptômes similaires à une pneumonie, une polysérosite fibrineuse, une polyarthrite et une méningite. Macleaya cordata, un médicament utilisé couramment en médecine traditionnelle chinoise, a été montré comme ayant des propriétés anti-inflammatoire, antivirale, anti-oxydative, antimicrobienne, insecticide et anti-tumeur. Toutefois, les effets anti-inflammatoires de M. cordata sur une stimulation par G. parasuis sont toujours peu compris. La présente étude explore les effets et mécanismes anti-inflammatoires d'un extrait de M. cordata sur les réponses inflammatoires induites par G. parasuis, via le facteur nucléaire-kappa B (NF-κB) et la voie de signalisation de la protéine kinase activée par les mitogènes (MAPK), dans les macrophages alvéolaires porcins (PAMs). Les PAMs, lorsque stimulés par G. parasuis, ont initié la transcription des interleukines (IL)-1α, IL-1ß, IL-6, IL-8, et le facteur de nécrose des tumeurs alpha (TNF-α). Également, la phosphorylation de p65, IκBα, p38, de la kinase régulée par signal extracellulaire (ERK), et de la kinase c-Jun N-terminal (JNK) était régulée à la hausse via les voies de signalisation NF-κB and MAPK. Toutefois, le traitement avec l'extrait de M. cordata a inhibé la transcription d'IL-1α, IL-1ß, IL-6, IL-8, et TNF-α et a diminué la phosphorylation de p65, IκBα, p38, ERK, et JNK, en inhibant les voies de signalisation de NF-κB et MAPK dans les PAMs induits par G. parasuis. Ces trouvailles révèlent qu'un extrait de M. cordata peut renverser l'effet inflammatoire initié par G. parasuis in vitro et qu'il possède une activité immunosuppressive significative; ainsi, ceci pourrait offrir une nouvelle stratégie pour limiter et traiter l'infection par G. parasuis.(Traduit par Docteur Serge Messier).

The effect of Macleaya cordata extract on in vitro ruminal fermentation and methanogenesis.

Methane production is the main gas energy loss in ruminants and generates a powerful greenhouse gas that contributes to climate changes. Macleaya cordata is a plant commonly utilized additive in livestock diet as it contains various chemical compounds with beneficial health effects. This study aimed to explore the influence of M. cordata extract on in vitro methanogenesis and rumen fermentation. Three cannulated Jingjiang cattle were used as rumen fluid donors. The mixture of rumen fluid and a buffer (60 ml, 1:2 volume ratio) was treated with 6 different concentrations of M. cordata extract (0.01%, 0.11%, 0.21%, 0.31%, 0.41%, and 0.51%) and incubated for 12 and 24 hr. The control sample, with no addition of plant extract, was also analyzed. At each time point, pH, total gas, methane, dry matter (DM) digestibility, neutral detergent fiber (NDF), acid detergent fiber (ADF), ammonia nitrogen (NH3-N), microbial protein (MCP), and volatile fatty acids (VFA) concentrations were determined. Total gas production decreased with increasing the amount of M. cordata extract at all time points. Methane production also decreased dose-dependently with M. cordata extract after 3, 6, 9, and 12 hr of incubation, but increased after 24 hr. M. cordata extract decreased the concentration of NH3-N and VFA, and the amount of acetic, propionic, and butyric acid. M. cordata extract decreased the MCP concentration after 12 hr, but its level returned to the initial value after 24 hr. Supplementation with 0.01, 0.11, and 0.21% of M. cordata extract did not affect the DM digestibility. However, supplementation with 0.31, 0.41, and 0.51% of M. cordata extract significantly decreased the DM digestibility. Supplementation with 0.11% of M. cordata extract effectively reduced methane production without affecting the DM digestion in vitro. However, its effect on in vivo methane production, rumen fermentation, and ruminant production requires further investigation.