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The development of acute liver injury can result in liver cirrhosis, liver failure, and even liver cancer, yet there is currently no effective therapy for it. The purpose of this study was to investigate the protective effect and therapeutic mechanism of Lycium barbarum polysaccharides (LBPs) on acute liver injury induced by carbon tetrachloride (CCl(4)). To create a model of acute liver injury, experimental canines received an intraperitoneal injection of 1 mL/kg of CCl(4) solution. The experimental canines in the therapy group were then fed LBPs (20 mg/kg). CCl(4)-induced liver structural damage, excessive fibrosis, and reduced mitochondrial density were all improved by LBPs, according to microstructure data. By suppressing Kelch-like epichlorohydrin (ECH)-associated protein 1 (Keap1), promoting the production of sequestosome 1 (SQSTM1)/p62, nuclear factor erythroid 2-related factor 2 (Nrf2), and phase II detoxification genes and proteins downstream of Nrf2, and restoring the activity of anti-oxidant enzymes like catalase (CAT), LBPs can restore and increase the antioxidant capacity of liver. To lessen mitochondrial damage, LBPs can also enhance mitochondrial respiration, raise tissue adenosine triphosphate (ATP) levels, and reactivate the respiratory chain complexes I‒V. According to serum metabolomics, the therapeutic impact of LBPs on acute liver damage is accomplished mostly by controlling the pathways to lipid metabolism. 9-Hydroxyoctadecadienoic acid (9-HODE), lysophosphatidylcholine (LysoPC/LPC), and phosphatidylethanolamine (PE) may be potential indicators of acute liver injury. This study confirmed that LBPs, an effective hepatoprotective drug, may cure acute liver injury by lowering oxidative stress, repairing mitochondrial damage, and regulating metabolic pathways.

Copper (Cu) is an essential trace element for growth and development in most organisms. However, environmental exposure to high doses of Cu can damage multiple organs. To investigate the underlying mechanism of Cu toxicity on mitochondrial dynamics and mitophagy in the cerebrum of pigs, 60 30-day-old pigs were randomly divided into three groups and treated with different contents of anhydrous Cu sulfate in the diets (Cu 10 mg/kg, control group; Cu 125 mg/kg, group I; Cu 250 mg/kg, group II) for 80 days. The Cu levels and histological changes in the cerebrum were measured. Moreover, the protein and mRNA expression levels related to mitophagy and mitochondrial dynamics were determined. The results showed that the contents of Cu were increased in the cerebrum with increasing dietary Cu. Vacuolar degeneration was found in group I and group II compared to the control group. Additionally, the protein and mRNA expression levels of PINK1, Parkin, and Drp1 and the protein level of LC3-II were remarkably upregulated with increasing levels of dietary Cu. Nevertheless, the protein and mRNA expression levels of MFN1 and MFN2 and the mRNA expression of P62 were obviously downregulated in a Cu dose-dependent manner. Overall, these results suggested that excess Cu could trigger mitochondrial dynamics disorder and mitophagy in the pig cerebrum, which provided a novel insight into Cu-induced toxicology.

Type 1 diabetes mellitus (T1DM) is a chronic disease represented by insulin-causing pancreatic β-cell disruption and hyperglycemia. Therefore, it is necessary to establish a variety of animal models of diabetes to study the pathogenesis and pathophysiology of it. However, there are few reports on the use of beagle dogs to establish an animal model of type 1 diabetes. This study aimed to explore a simple and feasible modeling method to establish a long-term and stable type 1 diabetes model in beagle dogs. Forty adult beagle dogs were randomly divided into control group and model group. After 24 h of fasting, streptozotocin (20 mg/kg) and alloxan (20 mg/kg) were injected through the cephalic vein. The second intravenous injection was given on the 4th day after the first injection. Insulin release testing was performed on the 7th day after the last intravenous injection. Fasting blood glucose and body weight were recorded monthly. Four months after the last injection, the serum fructosamine content and the ratio of glycated hemoglobin were detected. Then, the pancreatic tissue was harvested for histopathological examination. The results showed that the level of fasting blood glucose of the 16 dogs in the model group was consistently higher than 11.1 mmol/L for 4 consecutive months. Moreover, compared with the control group, the insulin release curve of the model group was flat with no increase. The body weight of the model group was significantly reduced, and the ratios of blood glucose, fructosamine, and glycosylated hemoglobin were significantly higher than those in the control group. Meanwhile, histopathological examination of the pancreas showed that the islet beta cells appeared to have vacuoles or even necrosis. In the model group, pancreatic β-cells were damaged and insulin release was reduced. These results suggest that the above modeling methods can induce long-term and stable type 1 diabetes models in beagle dogs.

Copper (Cu) is one of the ubiquitous environmental pollutants which have raised wide concerns about the potential toxic effects and public health threat. For deeply investigating the nephrotoxicity induced by Cu, the effects of Cu on mitochondria-mediated apoptosis in kidney were first to analyze by combining metabolomics and molecular biology techniques. In this study, broiler chicks were fed with different contents of Cu (11, 110, 220, and 330 mg/kg Cu) for 49 d. The results of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and transmission electron microscope showed that Cu could induce apoptosis in kidney, characterized by the increasing of TUNEL-positive cells and mitochondrial vacuolation. 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 to mitochondrial metabolism. Meanwhile, the decreased mitochondrial membrane potential (MMP), increased mitochondrial membrane permeability and the change of mRNA and protein expression levels associated with mitochondria-mediated apoptosis and mitochondrial dynamics confirmed that Cu could induce mitochondria-mediated apoptosis. Therefore, our results demonstrated that Cu induced mitochondria-mediated apoptosis in kidney. Moreover, this study highlighted the metabolic characteristics of Cu to kidney, which suggested that mitochondrial metabolism could be considered as an important factor influencing toxicity.