Oxidative Stress in Liver Disease

Liver, being the second largest organ, maintains homeostasis by undergoing a number of risk factors that include alcohol, drugs, environmental pollutants, and radiation. All these factors are capable of inducing oxidative stress by generating free radicals that eventually result in various forms of severe liver diseases. In this chapter, the consequences of oxidative stress are studied, along with its pathophysiology, its effects on organelles, physiological alterations, and the common diseases that occur due to oxidative stress. The progression of various liver diseases primarily involves lipid peroxidation, deoxyribonucleic acid (DNA) damage, signaling of inflammatory mediators, and ultimately generation of free radicals. The inarguable role of prooxidants in hepatic pathogenesis can be evidenced by an increase in the levels of biomarkers of oxidative stress, namely, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), to name a few. These markers are paralleled by utilizing endogenous antioxidant mechanisms, thus decreasing the levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione (GSH). This challenge was overcome by a diverse and rapid development in the field of biomarkers and antioxidants. Newer advances in the field of biomarkers outlined strategies to identify diseases at an early stage so that the treatment procedure could be both clinically useful and cost-effective. Advanced research on antioxidants, to treat liver disease, resulted in the emergence of natural substances that contain common natural herbal extracts, vitamins, and other compounds. Antioxidant use, either as a single compound or in combination, has become key molecules today for counteracting our stressed system and to achieve healthy homeostasis. However, new research should be carried out at cellular and molecular pharmacology levels in combination with drug targeting systems so as to get innovative ideas for the therapeutics of hepatic disease, which are not known enough

Edoxaban versus warfarin in patients with atrial fibrillation

Contains fulltext : 125374.pdf (publisher's version ) (Open Access)BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)