Ciliary neurotrophic factor analogue aggravates CCl4-induced acute hepatic injury in rats.

Ciliary neurotrophic factor (CNTF) and CNTF analogs were reported to have hepatoprotective effect and ameliorate hepatic steatosis in db/db or high-fat-diet-fed mice. Because hepatic steatosis and injury are also commonly induced by hepatotoxin, the aim of the present study is to clarify whether CNTF could alleviate hepatic steatosis and injury induced by carbon tetrachloride (CCl4). Unexpectedly, when combined with CCl4, CNTF aggravated hepatic steatosis and liver injury. The mechanism is associated with effects of CNTF that inhibited lipoprotein secretion and drastically impaired the ability of lipoproteins to act as transport vehicles for lipids from the liver to the circulation. While injected after CCl4 cessation, CNTF could improve liver function. These data suggest that CNTF could be a potential hepatoprotective agent against CCl4-induced hepatic injury after the cessation of CCl4 exposure. However, it is forbidden to combine recombinant mutant of human CNTF treatment with CCl4.

Alleviative effect of ciliary neurotrophic factor analogue on high fat-induced hepatic steatosis is partially independent of the central regulation.

Ciliary neurotrophic factor (CNTF) analogues were reported to ameliorate fatty liver in db/db or high-fat diet-fed mice. It is generally thought that CNTF exerts its actions centrally. The aim of this study was to investigate whether peripheral effects of CNTF analogues are involved in the therapeutic effect on high fat-induced hepatic steatosis. The rat model of fatty liver was induced by a high-fat diet (HFD) for 12 weeks. In the next 2 weeks, rats were fed the HFD along with subcutaneous injection of vehicle or mutant recombinant human CNTF (rhmCNTF 0.05-0.2 mg/kg per day). Steatotic HepG2 cells were induced by 50% fetal bovine serum (FBS) for 48 hours, and then treated with rhmCNTF for 24 hours. The results showed that after rhmCNTF treatment, hepatic triglyceride (TG) accumulation was attenuated both in vivo and in vitro. RhmCNTF increased protein expression of CPT-1 and PPARα, and decreased SREBP-1c, FAS and SCD-1 in steatotic HepG2 cells. But the production of nitric oxide and 8-isoPGF2α in steatotic HepG2 cells was not affected by rhmCNTF. These results suggest that rhmCNTF has a peripheral effect that alleviates fat-induced hepatic steatosis.

Ampelopsin sodium induces mitochondrial-mediated apoptosis in human lung adenocarcinoma SPC-A-1 cell line.

Ampelopsin is a well-known flavonoid which has variety of biological and pharmacological actions including anticancer effects and induction of apoptosis on the several cancer cell lines. The present study aimed to evaluate the role of ampelopsin sodium (Amp-Na) in the mitochondrial-mediated apoptosis of human lung adenocarcionma SPC-A-1 cells. The analysis of cell proliferation and ultrastructure were performed. Furthermore, to clarify its action mechanism by determining the mitochondrial membrane potential (Δψm), intracellular calcium (Ca2+) concentration, mitochondrial nitric oxide (NO) level and total ATPase activity. The results showed that Amp-Na markedly inhibited the SPC-A-1 cell proliferation and caused ultrastructural apoptosis feature in SPC-A-1 cells in a dose-dependent manner. Amp-Na led to a rapid and sustained Ca2+ elevation and Δψm reduction, and induced the mitochondrial NO production and decreased the total ATPase activity in SPC-A-1 cells. The results enhance the potential of Amp-Na as a therapeutic drug for treating lung cancer, and provide new information for mechanism of Amp-Na which induces mitochondrial-mediated apoptosis in tumor cells.

Effects of proanthocyanidins from grape seed on treatment of recurrent ulcerative colitis in rats.

The aim of the present study was to investigate the therapeutic effect and mechanism of proanthocyanidins from grape seed (GSPE) in the treatment of recurrent ulcerative colitis (UC) in rats. To induce recurrent colitis, rats were instilled with 2,4,6-trinitrobenzenesulfonic acid (TNBS) (80 mg/kg) into the colon through the cannula in the first induced phase, and then the rats were instilled a second time with TNBS (30 mg/kg) into the colon on the sixteenth day after the first induction UC. Rats were intragastrically administered GSPE (200 mg/kg) per day for 7 days after twice-induced colitis by TNBS. Sulfasalazine at 500 mg/kg was used as a positive control drug. Rats were killed 7 days after GSPE treatment. The colonic injury and inflammation were assessed by macroscopic and macroscopic damage scores, colon weight/length ratio (mg/cm), and myeloperoxidase activity. Then, superoxide dismutase, glutathione peroxidase, inducible nitric oxide synthase (iNOS) activities, and the levels of malonyldialdehyde, glutathione, and nitric oxide in serum and colonic tissues were measured. Compared with the recurrent UC group, GSPE treatment facilitated recovery of pathologic changes in the colon after induction of recurrent colitis, as demonstrated by reduced colonic weight/length ratio and macroscopic and microscopic damage scores. The myeloperoxidase and iNOS activities with malonyldialdehyde and nitric oxide levels in serum and colon tissues of colitis rats were significantly decreased in the GSPE group compared with those in the recurrent UC group. In addition, GSPE treatment was associated with notably increased superoxide dismutase, glutathione peroxidase activities, and glutathione levels of colon tissues and serum of rats. GSPE exerted a protective effect on recurrent colitis in rats by modifying the inflammatory response, inhibiting inflammatory cell infiltration and antioxidation damage, promoting damaged tissue repair to improve colonic oxidative stress, and inhibiting colonic iNOS activity to reduce the production of nitric oxide.

Therapeutic effects of a recombinant mutant of the human ciliary neurotrophic factor in a mouse model of metabolic syndrome.

Metabolic syndrome (MS) is highly prevalent in developed countries and becoming a serious worldwide public health issue. In this study, we established a MS model by feeding male C57BL/6J mice with a high-fat diet (10%) for 18.5 weeks, studied the therapeutic effects of a recombinant mutant of the human ciliary neurotrophic factor (rhmCNTF) 0.1 (C-0.1) or 0.3 (C-0.3) mg x kg(-1) per day subcutaneously or pair feeding (PF, which mice were restricted to the same amount of food as eaten by C-0.3 treated mice) in MS mice. After 10 days treatment, rhmCNTF reduced obesity related indices, ameliorated glucose and lipid metabolism abnormality, and enhanced insulin sensitivity. In addition, liver function and antioxidant ability of MS mice were improved by rhmCNTF. Pair feeding revealed the same effects as C-0.3 on obesity related indices and insulin sensitivity, but aggravated hepatic steatosis and hepatic function. The results suggest that rhmCNTF could serve as an effective therapeutic agent for MS and related diseases.

Cell death, dysglycemia and myocardial infarction.

Dysglycemia (hyper- and hypoglycemia) has been associated with higher mortality among patients suffering from myocardial infarction (MI). Moreover, dysglycemia may induce cell death. Cell death (necrosis, apoptosis and autophagy) is a ubiquitous process that characterizes the course of several diseases, including MI, and occurs in diverse forms varying in mechanism, pattern and consequence. Therefore, cell death is a potential pathway through which dysglycemia affects the outcome of MI and it is essential to regulate myocardial cell death in the treatment of patients with MI caused by dysglycemia. In this review, we summarized the mechanisms of MI at the cellular level and the regulatory effects of dysglycemia on myocardial cell death. The ability to modulate myocardial cell death may be a promising target of new treatments aimed at limiting MI caused by dysglycemia. However, further research is required to elucidate the mechanisms underlying cell death regulation in MI caused by dysglycemia.