Hepatotoxic mechanism of diclofenac sodium on broiler chicken revealed by iTRAQ-based proteomics analysis

Abstract

Background At the therapeutic doses, diclofenac sodium (DFS) has few toxic side effects on mammals. On the other hand, DFS exhibits potent toxicity against birds and the mechanisms remain ambiguous. Objectives This paper was designed to probe the toxicity of DFS exposure on the hepatic proteome of broiler chickens. Methods Twenty 30-day-old broiler chickens were randomized evenly into two groups (n = 10). DFS was administered orally at 10 mg/kg body weight in group A, while the chickens in group B were perfused with saline as a control. Histopathological observations, serum biochemical examinations, and quantitative real-time polymerase chain reaction were performed to assess the liver injury induced by DFS. Proteomics analysis of the liver samples was conducted using isobaric tags for relative and absolute quantification (iTRAQ) technology. Results Ultimately, 201 differentially expressed proteins (DEPs) were obtained, of which 47 were up regulated, and 154 were down regulated. The Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to screen target DEPs associated with DFS hepatotoxicity. The regulatory relationships between DEPs and signaling pathways were embodied via a protein-protein interaction network. The results showed that the DEPs enriched in multiple pathways, which might be related to the hepatotoxicity of DFS, were “protein processing in endoplasmic reticulum,” “retinol metabolism,” and “glycine, serine, and threonine metabolism.” Conclusions The hepatotoxicity of DFS on broiler chickens might be achieved by inducing the apoptosis of hepatocytes and affecting the metabolism of retinol and purine. The present study could provide molecular insights into the hepatotoxicity of DFS on broiler chickens.

Phosphoproteomics Profile of Chicken Cecum in the Response to Salmonella enterica Serovar Enteritidis Inoculation

“…Apoptosis (programmed cell death) is a universal form of death regulated by genes, which is crucial for normal organismal development and homeostasis [50]. Research has indicated that the hepatotoxicity of diclofenac sodium (DFS) may be achieved by inducing hepatocyte apoptosis through the endoplasmic reticulum pathway [38]. In our work, some of the up-and down-regulated DPPs were enriched in apoptosis and protein processing in endoplasmic reticulum KEGG pathways.…”

“…Retinol, a fat-soluble vitamin, is converted to retinaldehyde and retinoic acid in the liver to maintain the normal physiological functions, such as growth, vision, immunity, and antioxidation [36,37]. Retinol and its derivatives can improve the capabilities of antioxidation and scavenging free radicals to reduce the risk of inflammation and oxidative stress [38]. The extracellular matrix (ECM) is a part of the connective tissue layers surrounding muscle fibers.…”

Exploring the hepatoprotective effects of silymarin in experimentally induced- diclofenac sodium toxicity in rabbits

“…The hepatic metabolism of diclofenac sodium results in the development of hepatic disorders (Jeon et al, 2021). By inhibiting cyclooxygenase, diclofenac sodium hinders the biological synthesis of prostaglandin from arachidonic acid; this activity impacts physiological functions including osmoregulation, reproduction, water transport, and immune defense in organisms (Sun et al, 2022). Furthermore, chronic and acute toxicity of diclofenac have detrimental effects on marine life, disrupting their regular physiological processes such as nutrition, reproduction, swimming, development, and growth, ultimately threatening their survival.…”