Berberine (BBR) is a natural alkaloid with multiple biotical effects that has potential as a treatment for fatty liver hemorrhagic syndrome (FLHS). However, the mechanism underlying the protective effect of BBR against FLHS remains unclear. The present study aimed to investigate the effect of BBR on FLHS induced by a high-energy, low-protein (HELP) diet and explore the involvement of the gut microbiota and bile acid metabolism in the protective effects. A total of 90 healthy 140-day-old Hy-line laying hens were randomly divided into three groups, including a control group (fed a basic diet), a HELP group (fed a HELP diet), and a HELP+BBR group (high-energy, high-protein diet supplemented with BBR instead of maize). Our results show that BBR supplementation alleviated liver injury and hepatic steatosis in laying hens. Moreover, BBR supplementation could significantly regulate the gut’s microbial composition, increasing the abundance of Actinobacteria and Romboutsia. In addition, the BBR supplement altered the profile of bile acid. Furthermore, the gut microbiota participates in bile acid metabolism, especially taurochenodeoxycholic acid and α-muricholic acid. BBR supplementation could regulate the expression of genes and proteins related to glucose metabolism, lipid synthesis (FAS, SREBP-1c), and bile acid synthesis (FXR, CYP27a1). Collectively, our findings demonstrate that BBR might be a potential feed additive for preventing FLHS by regulating the gut microbiota and bile acid metabolism.

Hexavalent chromium (Cr(VI)) is a hazardous substance that poses significant risks to environmental ecosystems and animal organisms. However, the specific consequences of Cr(VI) exposure in terms of liver damage remain incompletely understood. This study aims to elucidate the mechanism by which Cr(VI) disrupts mitochondrial dynamics, leading to hepatic injury in ducks. Forty-eight healthy 8-day-old ducks were divided into four groups and subjected to diets containing varying doses of Cr(VI) (0, 9.28, 46.4, and 232 mg/kg) for 49 days. Our results demonstrated that Cr(VI) exposure resulted in disarranged liver lobular vacuolation, along with increasing the serum levels of ALT, AST, and AKP in a dose-dependent manner, which indicated liver damage. Furthermore, Cr(VI) exposure induced oxidative stress by reducing the activities of T-SOD, SOD, GSH-Px, GSH, and CAT, while increasing the contents of MDA and H₂O₂. Moreover, Cr(VI) exposure downregulated the activities of CS and MDH, resulting in energy disturbance, as evidenced by the reduced AMPK/p-AMPK ratio and PGC-1α protein expression. Additionally, Cr(VI) exposure disrupted mitochondrial dynamics through decreased expression of OPA1, Mfn1, and Mfn2 and increased expression of Drp-1, Fis1, and MFF proteins. This disruption ultimately triggered mitochondria-mediated apoptosis, as evidenced by elevated levels of caspase-3, Cyt C, and Bax, along with decreased expression of Bcl-2 and the Bcl-2/Bax ratio, at both the protein and mRNA levels. In summary, this study highlights that Cr(VI) exposure induces oxidative stress, inhibits the AMPK-PGC-1α pathway, disrupts mitochondrial dynamics, and triggers liver cell apoptosis in ducks.

The health problem of infertility has garnered increasing attention, prompting a deeper understanding of its causes. The broad-spectrum and nonselective herbicide glufosinate ammonium (GLA) is widely used in many countries. Previous studies have demonstrated the reproductive toxicity of GLA, but its potential toxic mechanisms remain unclear. Here, mice, Sertoli cells, and Leydig cells were used to create GLA preconditioning models. Results showed that GLA exposure caused morphological and functional damage of sperm. Concurrently, our study revealed that GLA, similar to Erastin, could induce ferroptosis in Sertoli and Leydig cells, as indicated by the dose-dependent increases of intracellular iron levels, lipid peroxidation, and cell death. Additionally, both the lipid ROS scavenger Fer and the iron chelator deferiprone were found to mitigate GLA-induced cell death. Intriguingly, our findings suggested that GLA-induced ferroptosis was dependent on autophagy, as the use of pharmacological inhibitors (3-methyladenine, chloroquine, and bafilomycin A1) or autophagy-related gene 5 gene knockout markedly reduced ferroptosis induced by GLA. We also demonstrated that nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy, which involves the autophagic degradation of the primary intracellular iron storage protein ferritin, is essential for GLA-induced ferroptosis by showing that NCOA4 knockdown decreased intracellular iron levels and attenuated lipid peroxidation, eventually alleviating GLA-induced cell death. Moreover, we observed that inhibition of the AMP-activated protein kinase–Unc-51-like kinase 1 (AMPK-ULK1) pathway activity by knockdown of AMPK expression markedly reduced the mitochondrial reactive oxygen species (mtROS) level and alleviated GLA-induced ferroptosis. Collectively, GLA induced excessive mtROS production through activation of the AMPK-ULK1 pathway, triggering excessive autophagy that ultimately led to ferroptosis via NCOA4-mediated ferritinophagy.