Sneha Hande1, Vijay Sonkar2, Priyanka Bhoj1, Namdev Togre1, Kalyan Goswami3, Debabrata Dash4. 1. Department of Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, 442 102, India. 2. Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Uttar Pradesh, Varanasi, 221 005, India. 3. Department of Biochemistry, All India Institute of Medical Sciences, Kalyani, West Bengal, 741 245, India. goswamikln@gmail.com. 4. Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Uttar Pradesh, Varanasi, 221 005, India. ddash.biochem@gmail.com.
Abstract
PURPOSE: Silver nanoparticles (AgNPs) mediated apoptosis is well-known but its rationale is yet to be elucidated. This study explored the mechanistic underpinning of the apoptosis in the Brugia malayi parasitic model. METHOD: Silver nanoparticles were synthesized and tested against B. malayi microfilariae (Mf) to explore the role of oxidative and nitrosative stress in its apoptotic effect. RESULTS: AgNPs caused significant decrease in reduced glutathione (GSH) level and increase in both protein carbonylation and nitric oxide (NO) level indicating oxidative as well as nitrosative stress. Both GSH and nitric oxide synthase (NOS) inhibitors exhibited marked reversal. Nanoparticles and NO-donor in combination but not the NO-donor alone showed significant antiparasitic effect implying the requisite of combined oxidative and nitrosative stress to induce apoptosis. Synthetically prepared peroxynitrite from NaNO2 to H2O2 showed marked antiparasitic effect in very low dose which could be achieved neither by NaNO2 or H2O2 alone. GSH reversed the effect of peroxynitrite similar to its specific inhibitor, acetaminophen. GSH also reversed the plummet in mitochondrial oxygen consumption by AgNPs. CONCLUSION: We conclude that apoptosis by AgNPs is possibly mediated through peroxynitrite dependent depletion of GSH; this provides a significant insight into the pharmacological as well as toxicological impact of AgNPs.
PURPOSE: Silver nanoparticles (AgNPs) mediated apoptosis is well-known but its rationale is yet to be elucidated. This study explored the mechanistic underpinning of the apoptosis in the Brugia malayi parasitic model. METHOD: Silver nanoparticles were synthesized and tested against B. malayi microfilariae (Mf) to explore the role of oxidative and nitrosative stress in its apoptotic effect. RESULTS: AgNPs caused significant decrease in reduced glutathione (GSH) level and increase in both protein carbonylation and nitric oxide (NO) level indicating oxidative as well as nitrosative stress. Both GSH and nitric oxide synthase (NOS) inhibitors exhibited marked reversal. Nanoparticles and NO-donor in combination but not the NO-donor alone showed significant antiparasitic effect implying the requisite of combined oxidative and nitrosative stress to induce apoptosis. Synthetically prepared peroxynitrite from NaNO2 to H2O2 showed marked antiparasitic effect in very low dose which could be achieved neither by NaNO2 or H2O2 alone. GSH reversed the effect of peroxynitrite similar to its specific inhibitor, acetaminophen. GSH also reversed the plummet in mitochondrial oxygen consumption by AgNPs. CONCLUSION: We conclude that apoptosis by AgNPs is possibly mediated through peroxynitrite dependent depletion of GSH; this provides a significant insight into the pharmacological as well as toxicological impact of AgNPs.
Authors: Amanda Cañas; Laura M López-Sánchez; Araceli Valverde-Estepa; Vanessa Hernández; Elena Fuentes; Juan R Muñoz-Castañeda; Chary López-Pedrera; Juan R De La Haba-Rodríguez; Enrique Aranda; Antonio Rodríguez-Ariza Journal: Breast Cancer Res Date: 2012-12-05 Impact factor: 6.466