Antioxidant potential of all-transretinoic acid (ATRA) and enhanced activity of liposome encapsulated ATRA against inflammation and tumor-directed angiogenesis

Abstract

The purpose of this study was to investigate whether all-trans retinoic acid (ATRA) has antioxidant property. The study was also focused on its inhibitory effect on the acute and chronic inflammation and tumor-associated capillary formation in terms of angiogenesis in C57BL/6 mice after incorporated in liposome composed of distearoylphosphatidylcholine (DSPC/cholesterol). ATRA possesses a number of important biologic activities including oncostatic, antioxidant and immunostimulatory actions. Our study was designed to evaluate the antioxidant activity of free ATRA by nitric oxide scavenging, superoxide radical scavenging, hydroxyl radical scavenging and lipid peroxide scavenging assays. The ATRA showed significant scavenging activities in all these antioxidant assays comparable to the standard antioxidant. We have also evaluated the activity of encapsulated ATRA against anti-inflammatory activity in C57BL/6 mice. The paw oedema inhibition was found in carrageenan model as 55.56% and 66.67% for free ATRA and encapsulated ATRA treatment respectively and for formaldehyde model it was found to be 60.87% and 69.57% respectively compared with saline treated control mice. Encapsulated ATRA inhibited the tumor-associated capillary formation in mice induced by highly metastatic B16F10 melanoma cells significantly than the free ATRA did. In this study the inhibition of tumor-directed capillary formation was found to be 56.25% and 62.50% for free ATRA and encapsulated ATRA treatment respectively. In conclusion, ATRA showed a significant antioxidant property in vitro. Free ATRA has anti-inflammatory activity as proved by us in animal model of acute and chronic inflammation and antiangiogenesis activity. Furthermore, its activity was boosted by encapsulation in liposome.

Metabolite profiling, antioxidant and antibacterial activities of Brazilian propolis: Use of correlation and multivariate analyses to identify potential bioactive compounds

“…A recent study has evaluated the antioxidant capacity of free retinoic acid by four different scavenging assays. The results showed significant scavenging activities in all these antioxidant assays comparable to the standard antioxidant (Siddikuzzaman & Grace, 2013). Although a high correlation between phenolic compounds and antioxidant capacity is expected, these results highlight the robustness of our approach to identify potential bioactive compounds.…”

Anti-Metastatic Study of Liposome-Encapsulated AlltransRetinoic Acid (ATRA) in B16F10 Melanoma Cells-Implanted C57BL/6 Mice

“…Regardless of exact mechanisms, here we clearly showed that the ATRA-induced inhibition of tumor nodule formation correlated well with increased lifespan in lung tumor bearing mice. The drug dose used for the present study did not appear to be highly toxic to the B16F10 cells as we have reported earlier (35). By controlling the concentration of ATRA during the preparation of liposome, we could get liposome-encapsulated ATRA in which ATRA was loaded at about 85% yield.…”

All trans retinoic acid (ATRA) mediated modulation of N-methyl D-aspartate receptor (NMDAR) and Kruppel like factor 11 (KLF11) expressions in the mitigation of ethanol induced alterations in the brain

“…ATRA has been reported to regulate the differentiation of serotonergic neurons (Fu et al, 2013), thereby promoting neuronal proliferation and regeneration (Hu et al, 1996;Lane andBailey, 2005, Ito andMorita, 1995), whereas chronic alcoholism adversely affects these processes and prevent adult neurogenesis (Valenzuela, 1997). Vitamin A and retinoids, which are redox-active molecules, exert antioxidant action at low concentration and pro-oxidant effects at high vitamin concentration (Lee et al, 2009;Siddikuzzaman, 2013). Our study involved supplementation of ATRA at low doses and the results clearly show reduction in oxidative stress due to ATRA supplementation, which may contribute to the observed protective effect of ATRA.…”

“…Vitamin A and retinoids are redox molecules and they have an antioxidant action at low concentration and pro-oxidant effects at high vitamin concentration (Lee et al, 2009;Siddikuzzaman, 2013). Supplementation of low dose retinoids against alcohol induced developmental damage was demonstrated in zebra fish embryos (Marrs et al, 2010).…”

“…Besides retinoids are known to promote and regulate adult neurogenesis whereas ethanol adversely affects adult neurogenesis causing neurodegeneration. All trans retinoic acid (ATRA), the active form of vitamin A metabolites, has been proven to enhance the ability of multipotent progenitor cells in differentiation (Siddikuzzaman, 2013). Retinoids have also been found to exert its effects on gabaergic and dopaminergic signaling in the brain.…”