Chronic alcohol consumption, type 2 diabetes mellitus, insulin-like growth factor-I (IGF-I), and growth hormone (GH) in ethanol-treated diabetic rats

AbstractAimsAlcohol has deleterious influences on glucose metabolism which may contribute to the development of type 2 diabetes mellitus (T2DM). Insulin-like growth factor I (IGF-I) and growth hormone (GH), which interact with insulin to modulate metabolic control, have been shown to be related to impaired glucose tolerance. This study was conducted to assess the possibility that altered circulating IGF-I and GH levels contribute to the exacerbation of T2DM by alcohol use in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats.Main methodOLETF rats were pair-fed a Lieber-DeCarli Regular Ethanol diet and LETO rats were pair-fed a control diet for 6weeks. At 6weeks, an Intraperitoneal Glucose Tolerance Test (IP-GTT) was performed and IGF-I and GH levels were evaluated.Key findingsPrior to an IP-GTT, OLETF-Ethanol (O-E) group had significantly a decrease in the mean glucose levels compared to OLETF-Control (O-C) group. At 120min post IP-GTT, the O-E group had significantly an increase in the mean glucose levels compared to O-C group. The serum IGF-I levels were significantly lower and the serum GH levels were significantly higher in the O-E group than in L-C group.SignificanceThese results suggest that IGF-I and GH are prominent in defining the risk and development of T2DM, and may be adversely affected by heavy alcohol use, possibly mediating its diabetogenic effects. Thus, the overall glucose intolerance in the setting of alcoholism may be attributable to inappropriate alteration of IGF-I and GH levels

Ultraviolet-c haematogenous oxidation therapy of lipopolysaccharide-induced endotoxemia in a rabbit model: A biochemical study

Systemic inflammatory reaction – due to severe response to toxins of infection associated with immune inhibition – leads to multi-organ dysfunctions and high mortality. Ultraviolet (UV) blood is used for its therapeutic effects when moving across the cells. This study aims to evaluate the impact of UV-c Haematogenous Oxidation Therapy (HOT) in Lipopolysaccharide (LPS)-induced endotoxemia of rabbit model. A total of 40 rabbits randomly divided into four groups, including normal control (NC). LPS and LPS+UV-c HOT groups received 0.1 mg/kg LPS toxin of E. coli, UV-c HOT and LPS+UV-c HOT groups subjected to UV-c HOT treatments once weekly for five times. Blood collected, perfused with oxygen, UV-c directly irradiated into blood, and then auto-transfused. Rabbits were sacrificed after five weeks; blood and serum were collected for analysis. The survival rate, liver, kidney, lipid profile, and blood ions were assessed in treated rabbits. Mortality was 40% in the LPS group, while other groups showed no death. UV-c HOT enhanced critical pH, base deficit, blood gases, hypomagnesemia, hyperlactatemia, and concurrent acidosis. Besides, TNF-α, nitrite, and nitrate were suppressed in response to UV-c HOT. Moreover, UV-c HOT reduced liver and kidney enzymes, improved lipid metabolism, and ameliorated electrolytes homeostasis. Despite that, UV-c HOT performance in ICU for human and animal endotoxemic or septic patients should be evaluated and considered

Ultraviolet-C haematogenous oxidation therapy of lipopolysaccharide-induced endotoxemia in a rabbit model: A biochemical study

445-454Systemic inflammatory reaction – due to severe response to toxins of infection associated with immune inhibition – leads to multi-organ dysfunctions and high mortality. Ultraviolet (UV) blood is used for its therapeutic effects when moving across the cells. This study aims to evaluate the impact of UV-C Haematogenous Oxidation Therapy (HOT) in Lipopolysaccharide (LPS)-induced endotoxemia of rabbit model. A total of 40 rabbits randomly divided into four groups, including normal control (NC). LPS and LPS+UV-C HOT groups received 0.1 mg/kg LPS toxin of E. coli, UV-C HOT and LPS+UV-C HOT groups subjected to UV-C HOT treatments once weekly for five times. Blood collected, perfused with oxygen, UV-C directly irradiated into blood, and then auto-transfused. Rabbits were sacrificed after five weeks; blood and serum were collected for analysis. The survival rate, liver, kidney, lipid profile, and blood ions were assessed in treated rabbits. Mortality was 40% in the LPS group, while other groups showed no death. UV-C HOT enhanced critical pH, base deficit, blood gases, hypomagnesemia, hyperlactatemia, and concurrent acidosis. Besides, TNF-α, nitrite, and nitrate were suppressed in response to UV-C HOT. Moreover, UV-C HOT reduced liver and kidney enzymes, improved lipid metabolism, and ameliorated electrolytes homeostasis. Despite that, UV-C HOT performance in ICU for human and animal endotoxemic or septic patients should be evaluated and considered

Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes.

Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH

Altered expression of norepinephrine transporter and norepinephrine in human placenta cause pre-eclampsia through regulated trophoblast invasion

Objective: We investigated the norepinephrine transporter (NET) expression in normal and pre-eclamptic placentas and analyzed the invasion activity of trophoblastic cells based on norepinephrine (NE)-NET regulation. Methods: NET and NE expression levels were examined by western blot and enzyme-linked immunosorbent assay, respectively. Trophoblast invasion activity, depending on NE-NET regulation, was determined by NET-small interfering RNA (siRNA) and NET transfection into the human extravillous trophoblast cells with or without NE treatment and invasion rates were analyzed by zymography and an invasion assay. Results: NET mRNA was expressed at a low level in pre-eclamptic placentas compared with normal placentas and NE concentration in maternal plasma increased significantly in pre-eclamptic women compared to normal pregnant women (p<0.05). NET gene upregulation and NE treatment stimulated trophoblast cell invasion up to 2.5-fold (p<0.05) by stimulating matrix metalloproteinase-9 activity via the phosphoinositol-3-kinase/AKT signaling pathway, whereas NET-siRNA with NE treatment reduced invasion rates. Conclusion: NET expression is reduced by inadequate regulation of NE levels during placental development. This suggests that a complementary balance between NET and NE regulates trophoblast cell invasion activities during placental development