Metabolomics Reveals the Effects of Copper on Mitochondria-mediated Apoptosis in Kidney of Chicken (Gallus Gallus)

Abstract

Background: Copper (Cu), a common feed additive in diets for animals, is effective in improving growth performance and feed efficiency. However, excessive intake of Cu can cause toxic effects. Kidney is the main target organ of Cu, but the relationship between Cu-induced nephrotoxicity and its metabolic process remains unclear.Results: For deeply investigating the nephrotoxicity induced by Cu, a total of 240 broiler chicks were fed with different contents of Cu (11, 110, 220, and 330 mg/kg Cu) for 49 d in this study (60 chicks per group). The results of TUNEL staining showed that Cu could induce apoptosis in kidney with increasing of TUNEL-positive cells. Additionally, a total of 62 differential metabolites were detected by liquid chromatography-mass spectrometry (LC-MS), and mainly enriched in the metabolic pathways including riboflavin metabolism, glutathione metabolism, sphingolipid metabolism, and glycerophospholipid metabolism, which were closely related to mitochondrial metabolism. Meanwhile, the decrease of mitochondrial membrane potential, impairment of mitochondrial respiratory function, and the increase of mitochondrial membrane permeability indicated that renal mitochondria were damaged by excess Cu. Furthermore, the increase of mRNA and protein levels of Drp1, Bax, Bak-1, CytC, Caspase-3/cleaved Caspase-3 and the decrease of mRNA and protein levels of OPA1, Mfn1, Mfn2, and Bcl-2 confirmed that Cu could induce mitochondria-mediated apoptosis in kidney.Conclusions: These results highlighted that mitochondrial metabolism could be considered as an important factor in influencing Cu toxicity, which for further demonstrating that Cu could induce mitochondria-mediated apoptosis in kidney of broilers.

Glucose oxidase as an alternative to antibiotic growth promoters improves the immunity function, antioxidative status, and cecal microbiota environment in white-feathered broilers

“…This can be confirmed in this study as the Oscillibacter and Oscillospira genera in GOD (GOD600 and GOD1200) were significantly higher than those in control groups, and the trend in ZO-1 expression was the same between GOD and control groups. Moreover, based on human research, the significant Oscillospira decrease was associated with obesity-related chronic inflammatory and metabolic diseases (Yang J. et al, 2021). Hence, it may become a next-generation probiotic candidate for symptom relief in broilers.…”

“…The metabolic pathways, such as riboflavin metabolism, insect hormone biosynthesis, and secondary bile acid biosynthesis, displayed varying degrees of benefits for broilers. The riboflavin metabolism was reported to be related to mitochondria-mediated apoptosis, and the flavoprotein participating in this metabolism may contribute to superoxide production along with mitochondrial energy metabolism (Balasubramaniam and Yaplito-Lee, 2020;Liao et al, 2021). It implied that this metabolism might play a part in oxidative stress.…”