Changes of liver transcriptome profiles following oxidative stress in streptozotocin-induced diabetes in mice

Abstract

Background Oxidative-stress (OS) was causal in the development of cell dysfunction and insulin resistance. Streptozotocin (STZ) was an alkylation agent that increased reactive oxygen species (ROS) levels. Here we aimed to explore the oxidative-stress and related RNAs in the liver of STZ-induced diabetic mice. Methods RNA-sequencing was performed using liver tissues from STZ induced diabetic mice and controls. Pathway and Gene Ontology (GO) analyses were utilized to annotate the target genes. The differentially expressed RNAs involved in the peroxisome pathway were validated by qRT-PCR. The glucose metabolite and OS markers were measured in the normal control (NC) and STZ-induced diabetic mellitus (DM) group. Results The levels of serum Fasting insulin, HbA1c, Malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α) were significant higher in DM groups than NC group, while SOD activity decreased significantly in DM groups. We found 416 lncRNAs and 910 mRNAs were differentially expressed in the STZ-induced diabetic mice compared to the control group. OS associated RNAs were differentially expressed in the liver of STZ-induced diabetic mice. Conclusion This study confirmed that the OS was increased in the STZ-induced DM mice as evidenced by the increase of lipid peroxidation product MDA and 8-iso-PGF2α, identified aberrantly expressed lncRNAs and mRNAs in STZ-induced diabetic mice.

In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling

“…In toxin-based approaches, the so-called Stelic Animal Model (STAM) of NASH-hepatocarcinogenesis is widely established [ 170 , 173 , 174 ] ( Table 3 ). Low-dose administration of streptozotocin (STZ) in the first days of life of a mouse leads to oxidative injury in pancreatic islets and profound changes in hepatic transcriptomic profile [ 175 , 176 ]. This alkylating agent established diabetic conditions, usually absent in dietary interventions, which promote rapid lipogenesis, fatty acid oxidation, hepatocellular injury, and fibrosis [ 170 , 173 ].…”

“…Cell lines ( Table 8 and Table 9 ) are popular models for drug screening studies [ 256 ], drug safety testing [ 176 ], and studies related to liver disease [ 253 ] due to their ease of use, phenotypic stability and reproducibility. Human liver cell lines are typically immortalized by genetic engineering or selected based on their tumorigenic phenotype, implying they are derived from human tumors [ 253 , 274 ].…”

“…Spheroids can be derived from PHH and hepatic cell lines [ 361 ]. Most liver cell lines are less differentiated compared to PHH, which is mainly reflected by a lack of biotransformation capacity [ 176 , 253 , 256 ]. Throughout the years, 3D spheroid models have been introduced to tackle this shortcoming [ 291 , 293 ].…”

Effect of Hydroxytyrosol on Prdx6 Expression in Diabetic Rat Liver

“…Therefore, oxidative stress markers are quite high in the liver in the early stages of diabetes (3). The oxidative stress-induced liver injury affects insulin binding to the insulin receptor on the liver cell surface and insulin signaling (8). While this situation affects glucose and lipid balance negatively, it may also cause a large number of metabolic disorders (4).…”