Potential benefits of quinoxaline 1, 4-dioxides in aldosterone dysmetabolism disease—A medical hypothesis

Quinoxaline 1, 4-dioxides (QdNOs) are quinox-aline derivatives which have been used as an-timicrobial agents and growth promoters in animals widely. They are also assumed to cure human disease such as anticancer, antitubercular and inhibiting parasite. QdNOs such as carbadox and their major metabolites induced a special decline of aldosterone production from the swine adrenal in vivo and in vitro, and thus cause hypovolemia, hyponatremia and hyperkalemia. This can also be expected to be the case for human. As a mainly physiological hormone and a novel steroid with potent mineralocorticoid activity, aldosterone plays an important role in the pathophysiological process of brain, renal and heart disease progression and may be a renal and vascular risk factor. Here, we provide evidence to support the hypothesis that QdNOs may lead potential benefits in aldosterone dysmetabolism disease via the synthesis deficiency of aldosterone in adrenal and/or the cardiovascular tissues. If the hypothesis is true, it may provide a new option into the therapy for aldosterone dysmetabolism disease, especially in cardiovascular system, and thus assume a broader application of QdNOs.

Harpephyllum caffrum stimulates glucose uptake,abates redox imbalance and modulates purinergic and glucogenic enzyme activities in oxidative hepatic injury

Objective:To investigate the antioxidative and antidiabetic effects of Harpephyllum caffrum bark infusion as well as its effects on glucogenic and nucleotide hydrolyzing enzyme activities in FeSO4-induced oxidative stress in rat hepatic tissue.Methods:Harpephyllum caffrum infusion was prepared from dried plant materials(40 g)infused in boiling water(400 mL)for 20 min at room temperature.The antioxidative and inhibitory activities against carbohydrate digestive enzymes of the infusion were determined using established protocols.The liver tissues of rats were used for glucose uptake assay and to evaluate the infusion’s effect on endogenous antioxidant,glucogenic,and nucleotide hydrolyzing enzyme activities in FeSO4-induced hepatic injury.Results:The Harpephyllum caffrum infusion significantly reduced ferric iron(FRAP)and free radicals(OH•and DPPH)in a dose-dependent manner.It inhibitedα-amylase andα-glucosidase activities and increased glucose uptake in hepatic tissues.FeSO4 significantly decreased glutathione concentration,catalase,and superoxide dismutase activities while increasing malondialdehyde level,glycogen phosphorylase,fructose-1,6-bisphosphatase,and adenosine triphosphatase activities.However,treatment with Harpephyllum caffrum infusion reversed FeSO4-induced changes.Characterization of the infusion revealed the presence of catechol,O-pyrocatechuic acid,mequinol,maltol,and glycoside derivatives.Conclusions:The Harpephyllum caffrum infusion demonstrates antidiabetic and antioxidative potentials in in vitro models of type 2 diabetes as depicted by its ability to inhibit carbohydrate digestive enzymes,mitigate oxidative imbalance,and regulate glucogenic and nucleotide hydrolyzing enzyme activities in oxidative hepatic injury.

Circadian dysrhythmia-linked diabetes mellitus: Examining melatonin's roles in prophylaxis and management

Diabetes mellitus is a chronic, life-threatening metabolic disorder that occurs worldwide. Despite an increase in the knowledge of the risk factors that are associated with diabetes mellitus, its worldwide prevalence has continued to rise; thus, necessitating more research into its aetiology. Recent researches are beginning to link a dysregulation of the circadian rhythm to impairment of intermediary metabolism; with evidences that circadian rhythm dysfunction might play an important role in the aetiology, course or prognosis of some cases of diabetes mellitus. These evidences thereby suggest possible relationships between the circadian rhythm regulator melatonin, and diabetes mellitus. In this review, we discuss the roles of the circadian rhythm in the regulation of the metabolism of carbohydrates and other macronutrients; with emphasis on the importance of melatonin and the impacts of its deficiency on car-bohydrate homeostasis. Also, the possibility of using melatonin and its analogs for the "prophylaxis" or management of diabetes mellitus is also considered.

Fatty liver is associated with an increased risk of diabetes and cardiovascular disease- Evidence from three different disease models: NAFLD, HCV and HIV

Fatty liver, which frequently coexists with necroinflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease(NAFLD) and chronic infections due to either hepatitis C virus(HCV) or human immunodeficiency virus(HIV). These three pathologic conditions are associated with an increased prevalence and incidence of cardiovascular disease(CVD) and type 2 diabetes(T2D). In this multidisciplinary clinical review, we aim to discuss the ever-expanding wealth of clinical and epidemiological evidence supporting a key role of fatty liver in the development of T2 D and CVD in patients with NAFLD and in those with HCV or HIV infections. For each of these three common diseases, the epidemiological features, pathophysiologic mechanisms and clinical implications of the presence of fatty liver in predicting the risk of incident T2 D and CVD are examined in depth. Collectively, the data discussed in this updated review, which follows an innovative comparative approach, further reinforce the conclusion that the presence of fatty/inflamed/fibrotic liver might be a shared important determinant for the development of T2 D and CVD in patients with NAFLD, HCV or HIV. This review may also open new avenues in the clinical and research arenas and paves the way for the planning of future, well-designed prospective and intervention studies.

Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver

Elevated iron stores as indicated by hyperferritinemiawith normal or mildly elevated transferrin saturation a n d m o s t l y m i l d h e p a t i c i r o n d e p o s i t i o n a r e a characteristic finding in subjects with non-alcoholic fatty liver disease(NAFLD). Excess iron is observed in approximately one third of NAFLD patients and is commonly referred to as the "dysmetabolic iron overload syndrome". Clinical evidence suggests that elevated body iron stores aggravate the clinical course of NAFLD with regard to liver-related and extrahepatic disease complications which relates to the fact that excess iron catalyses the formation of toxic hydroxylradicals subsequently resulting in cellular damage. Iron removal improves insulin sensitivity, delays the onset of type 2 diabetes mellitus, improves pathologic liver function tests and likewise ameliorates NAFLD histology. Several mechanisms contribute to pathologic iron accumulation in NAFLD. These include impaired iron export from hepatocytes and mesenchymal Kupffer cells as a consequence of imbalances in the concentrations of iron regulatory factors, such as hepcidin, cytokines, copper or other dietary factors. This review summarizes the knowledge about iron homeostasis in NAFLD and the rationale for its therapeutic implications.