Citicoline ameliorates arsenic-induced hepatotoxicity and diabetes in mice by overexpression of VAMP2, PPAR-γ, As3MT, and SIRT3.

The use of arsenic in arsenic-based pesticides has been common in many countries in the past and today. There is considerable evidence linking arsenic exposure to hepatotoxicity and diabetes. Destructive phenomena such as hepatic oxidative stress and inflammation can interfere with glucose uptake and insulin function. In the present study, the antioxidant, anti-inflammatory, and molecular mechanism of citicoline against sodium arsenite-induced hepatotoxicity and glucose intolerance were investigated in mice. Citicoline improved glucose tolerance impaired by sodium arsenite. Citicoline increased the hepatic activity of catalase, superoxide dismutase, and glutathione peroxidase enzymes. Moreover, we found that citicoline prevents an increase in the levels of thiobarbituric acid reactive substances. Citicoline reduced levels of caspase 3, tumor necrosis factor-alpha, and interleukin 6 in sodium arsenite intoxicated groups. It was shown that citicoline increased the expression of arsenite methyltransferase, vesicle-associated membrane protein 2, peroxisome proliferator-activated receptor gamma, and sirtuin 3 to combat sodium arsenite toxicity. Citicoline reduced glucose intolerance, which was disrupted by sodium arsenite, by affecting the pancreatic and extra-pancreatic pathways involved in insulin production, secretion, and action. Based on our results, citicoline can be considered a modulating agent against arsenic-induced hepatotoxicity and hyperglycemia. Considering the relationship between arsenic exposure and the occurrence of side effects such as liver toxicity and diabetes, it is necessary to monitor and awareness of arsenic residues from sources such as drinking water.

Clinical significance of SIRT3 and inflammatory factors in multiple myeloma patients with bortezomib-induced peripheral neuropathy: a cohort study.

The present study aimed to investigate the role of SIRT3 and inflammatory factors in bortezomib-induced peripheral neuropathy (PN). This prospective observational cohort study included a total of 159 patients of multiple myeloma patients during June 2016 to June 2019. All patients received the strategy of bortezomib and dexamethasone and were further divided into the PN group and the non-PN group. Serum SIRT3, CRP, IL-6 and TNF-α levels were measured by enzyme-linked immunosorbent assay (ELISA). During the study period, 76 (47.8%) patients developed PN. The inflammatory factors all gradually decreased and SIRT3 levels were gradually increased after treatment by bortezomib combined with dexamethasone compared with the baseline. The levels of all inflammatory factors were markedly higher, while SIRT3 levels were lower in PN patients compared with the non-PN patients at the same time point after treatment. In PN grade III patients, the serum levels of CRP, IL-6 and TNF-α were significantly higher, while serum levels of SIRT3 were markedly lower than the grade I-II patients. SIRT3 was negatively correlated with CRP, IL-6 and TNF-α. After nursing treatment and reduction of bortezomib dose, the levels of SIRT3 significantly increased, while levels of inflammatory decreased in PN patients with grade III. SIRT3 and inflammatory factors showed the potential for diagnosis of bortezomib-induced PN. Besides, SIRT3, IL-6 and TNF-α were the independent risk factors for MM patients developing PN after treatment of bortezomib. Higher inflammatory factors and lower SIRT3 might be associated with the development of bortezomib-induced PN in multiple myeloma patients, which might be reversed by decreased bortezomib dose and proper nursing treatment.