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Cadmium pollution is serious heavy metal pollution in environmental pollution and impacts on livestock productivity. However, the effect and mechanisms of cadmium toxicity on the broiler remain unclear. This study aimed to explore the liver oxidative damage and reveal the related long non-coding RNA (lncRNA) expression patterns in the broiler liver with cadmium exposure. The broilers were fed with diets containing CdCl2 and detected the oxidative stress indexes in the liver tissues. Transcriptome sequencing of broiler liver was performed to identify cadmium exposure-related differentially expressed lncRNAs (DElncRNAs). The functions and pathways of DElncRNAs were analyzed by GO and KEGG. The sequencing results were verified by the quantitative real-time polymerase chain reaction. Cadmium exposure induced tissue structure disorder, focal hemorrhage, and irregular hepatocytes in the broiler liver, and significantly decreased GSH level and enzyme activities, and increased MDA expression in the liver. A total of 74 DElncRNAs were obtained in cadmium group compared with the control group, which were enriched in the GO terms, including intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator, branched-chain amino acid biosynthetic process. The enriched KEGG pathways, including lysine biosynthesis, valine, leucine and isoleucine biosynthesis, and pantothenate and CoA biosynthesis, were related to oxidative stress. PCR analysis indicated that the changes in ENSGALG00000053559, ENSGALG00000053926, and ENSGALG00000054404 expression were consistent with sequencing. Our results provide novel lncRNAs involved in oxidative stress in the broiler liver with cadmium exposure.

A new losartan [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol zinc(II) complex [Zn(Los)Cl], was synthesized and characterized. The crystal structure was determined by x-ray diffraction methods. When aqueous solutions of the ligand and the metal were mixed, the known and more soluble powder [Zn(Los)₂].3H₂O (ZnLos) complex has been obtained. The interactions with phosphatases showed a concerted mechanism displayed by the Zn ions and ZnLos up to 500 μM concentration: a decrease of the acid phosphatase (AcP) associated with an increase in the alkaline phosphatase (ALP) activities. The complex and ZnSO₄ showed a cytotoxic behavior on human lung A549 cancer cell line at concentrations higher than 75 μM with reactive oxygen species (ROS) generation and GSH (and GSH/GSSG ratio) depletion. Apoptotic cells were observed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method, a mechanism accompanied by upregulation of BAX protein, downregulation of Bcl-XL and release of caspase-3. The BAX/Bcl-XL ratio was found to be significantly higher in cells exposure to ZnLos than cells treated with ZnSO₄, in agreement with the higher apoptotic percentage of cells found for the complex. Cell death was found to be produced by apoptosis and no necrosis has been observed. On the contrary, losartan exerted low effects on phosphatases, produced some reduction of cancer cell viability (concentrations > 250 μM, number of apoptotic cells similar to the basal) with low ROS depletion, without alteration of the GSH/GSSG and low BAX/Bcl-XL ratios. In the MRC-5, normal lung fibroblasts cell line only ZnSO₄ at concentrations higher than 200 μM displays cytotoxic effects., Centro de Química Inorgánica, Instituto de Física La Plata