1. N-acetyl-L-cysteine ameliorates hepatocyte pyroptosis of dog type 1 diabetes mellitus via suppression of NLRP3/NF-κB pathway
- Author
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Haihua Huo, Haitong Wu, Feiyang Ma, Xinrun Li, Jianzhao Liao, Lianmei Hu, Qingyue Han, Ying Li, Jiaqiang Pan, Hui Zhang, Zhaoxin Tang, and Jianying Guo
- Subjects
NF-kappa B ,General Medicine ,General Biochemistry, Genetics and Molecular Biology ,Streptozocin ,Acetylcysteine ,Rats ,Rats, Sprague-Dawley ,Diabetes Mellitus, Type 1 ,Dogs ,NLR Family, Pyrin Domain-Containing 3 Protein ,Hepatocytes ,Pyroptosis ,Animals ,Insulin ,General Pharmacology, Toxicology and Pharmaceutics - Abstract
Type 1 diabetes mellitus (T1DM) is a chronic and represented by insulin-causing pancreatic β-cell disruption and hyperglycemia. N-Acetyl-Cysteine (NAC) is regarded as facilitating endothelial cell function and angiogenesis and may have treatment effect in the case of diabetes. However, the impact of NAC on T1DM are unknown. Here we reported that inflammatory pathogenesis of canine type 1 diabetes liver disease and the therapeutic effect of NAC combined with insulin. For this purpose, the model was established by intravenous injection of streptozotocin (20 mg/kg). Forty adult dogs were used and divided into 5 groups: control group, DM group, insulin treatment group, NAC combined with insulin therapy, and NAC group, while study lasted for 16 weeks. Results showed that the level of liver function enzyme activity were apparently increased in DM group, while the NAC with insulin treatment remarkable decreased liver function enzyme levels. Histopathology revealed that obvious changes in liver structure of all DM group, as evidenced by hepatocyte disorder and cellular swelling. Liver structure was evaluated by Periodic Acid Schiff (PAS) and Masson staining, the tissues appeared glycogen deposition and collagen deposition, indicating that DM aggravated liver injury. Compared with control group, the protein and mRNA expression of NLRP3, Caspase-1, ASC, and GSDMD were significantly induced in the DM group, while INS and NAC combined with INS treatment reversed the above changes. The levels of NF-κB P65, p-NF-κB, and IFN γ were availably enhanced in the DM group, which decreased through insulin and NAC combined with insulin treatment. This study demonstrated that NAC combined with INS exerted protective effects against STZ-induced liver injury by inhibiting the NLRP3/NF-κB pathway. The findings indicated that NAC combined with INS may serve as a potential candidate therapy for the treatment of T1DM.
- Published
- 2022