Ammonia triggers ferroptosis in macrophages of yellow catfish Pelteobagrus fulvidraco

Abstract

An in vitro experiment was carried out to investigate the effect of ammonia on the macrophages of yellow catfish Pelteobagrus fulvidraco from a ferroptotic point of view.The fish macrophages were cultured with 0.00, 0.12, 0.23 and 0.46 mg/L ammonia for 24 h. The result showed that ammonia decreased the cell viability, reduced glutathione (GSH) contents and increased the reactive oxygen species (ROS) levels of fish macrophages. Meanwhile, the mRNA levels of systemX − c and ferritin light chain1 (FTL1) were down-regulated when ammonia concentration was elevated up to 0.12 mg/L.Compared with control, the mRNA level of glutathione peroxidase 4 (GPX4) was upregulated when ammonia was elevated up to 0.12 mg/L, but was down-regulated when ammonia reached 0.46 mg/L. Compared with control, the mRNA level of lipoxygenase (LOX)-12 was up-regulated when ammonia was elevated up to 0.12 mg/L, but was down-regulated when ammonia reached 0.23 mg/L, and the mRNA levels of LOX-5, LOX-15b and transferrin Receptor 1 (TFR1) were up-regulated when ammonia was elevated up to 0.12 mg/L, but was down-regulated when ammonia reached 0.23 mg/L. In conclusion, our study found that ammonia could trigger ferroptosis in the macrophage of fish.

Effects of Curcumin on Oxidative Stress and Ferroptosis in Acute Ammonia Stress-Induced Liver Injury in Gibel Carp (Carassius gibelio)

“…Impaired clearance or overproduction of lipid peroxide MDA can lead to its accumulation to lethal levels and trigger ferroptosis [ 25 ]. In our study, liver ROS and MDA levels were significantly stimulated by acute ammonia stress, similar to the results observed in yellow catfish ( Pelteobagrus fulvidraco ) [ 26 ]. Moreover, Nrf2, a key transcription factor that regulates resistance to oxidative stress, plays an essential role in the induction of antioxidant response in the organism [ 27 ].…”

“…GPX4 is a central regulator of lipid peroxidation and ferroptosis involved in the Fenton reaction [ 33 ]. A significant increase in the mRNA levels of hepatic ncoa4 and tfr1 and a significant decrease in the mRNA levels of p53 , gpx4 , fpn , and fth1 were induced by ammonia stress, indicating that hepatic ferroptosis was triggered by stimulating iron uptake and reducing iron storage, eventually leading to liver injury in gibel carp, similar to the effects in yellow catfish [ 26 ]. Thus, CUR affected the process of liver injury in gibel carp through the inhibition of the ferroptosis pathway.…”

Ferroptosis Induced by Pollutants: An Emerging Mechanism in Environmental Toxicology

“…Exposure to dexamethasone (DEX), a potent glucocorticoid, resulted in T-cell ablation and osteoporosis, possibly due to ferroptosis. Gan et al supported these findings by reporting that ammonia exposure could trigger ferroptosis in fish macrophages, thereby impacting the immune system …”

“…In a recent study, the impact of ammonia on yellow catfish was investigated from a ferroptotic perspective. 49 The findings revealed that ammonia exposure resulted in decreased cell viability, reduced GSH contents, and increased ROS levels in fish macrophages. Furthermore, the study showed downregulation of mRNA levels of system x c − and ferritin light chain 1 (FTL1) with elevated ammonia concentrations, while the mRNA levels of GPX4 and LOX isoforms exhibited varying patterns.…”

“…Gan et al supported these findings by reporting that ammonia exposure could trigger ferroptosis in fish macrophages, thereby impacting the immune system. 49 Taken together, these studies underscore the need for a more in-depth understanding of ferroptosis to develop effective strategies to minimize its potential adverse impacts on different biological systems and organisms. Such knowledge is crucial for devising comprehensive and targeted approaches to mitigate the harmful consequences of environmental pollutants on fish and their ecosystems.…”