Environmental Toxicology and Pharmacology 43 (2016) 27–37 Contents lists available at ScienceDirect Environmental Toxicology and Pharmacology j o ur na l ho mepage: www.elsevier.com/locate/etap Nanopharmaceutical approach using pelargonidin towards enhancement of efficacy for prevention of alloxan-induced DNA damage in L6 cells via activation of PARP and p53 Asmita Samadder a,∗ , Suresh K. Abraham a , Anisur Rahman Khuda-Bukhsh b a School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India b Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India a r t i c l e i n f o Article history: Received 9 August 2015 Received in revised form 9 February 2016 Accepted 10 February 2016 Available online 12 February 2016 Keywords: PLGA encapsulation Pelargonidin Alloxan DNA stability curve L6 cell line DNA repair cascade a b s t r a c t Alloxan is an environmental food contaminant that causes DNA damage in living cells and induces hyper- glycemia. Pelargonidin (PG), an active ingredient found in extract of various fruits and vegetables, has been nanoencapsulated (NPG) with poly-lactide-co-glycolide (PLGA) and tested for efficacy in preven- tion of alloxan (ALX)-induced DNA damage in L6 cells in vitro. Glucose uptake, reactive oxygen species (ROS) generation, glucose transporter 4, glucokinase levels and mechanism of activation of DNA repair proteins (PARP and p53) have been studied in ALX-induced L6 cells. Drug–DNA interaction has been analyzed using calf thymus DNA as target through circular dichroism and melting temperature profile. NPGs were physico-chemically characterized by standard protocols using dynamic light scattering and transmission electron microscopy. Pre-treatment with both PG and/or NPG was effective in reducing ALX-induced oxidative stress and showed favourable effects for protection against DNA damage by acti- vating DNA repair cascades. Results suggested ∼10-fold increase in efficacy of NPG than PG in prevention of alloxan-induced oxidative stress and DNA damage. © 2016 Elsevier B.V. All rights reserved. 1. Introduction Diabetes has emerged as a common metabolic disorder affecting a large section of the human population (Samadder et al., 2011). At present, many new antidiabetic drugs with minimum harmful side effects are being developed. In spite of that, herbal medicines with relatively less cytotoxic effects are becoming popular for treating diabetic patients. Hence, research on a wide variety of phytochem- ical combinations for treating diabetes (Samadder et al., 2011; Samadder and Khuda-Bukhsh, 2014; Roy et al., 2008) is gaining importance. Alloxan, an environmental food contaminant, which is consumed as a food item made up of flour (a staple food in a large part of the human population), is implicated to induce a con- dition of hyperglycemia in animal models in vivo as well as in vitro cultured cells including L6 cells (Lenzen and Panten, 1988). Anthocyanidins are non-toxic plant pigments found in orange, red, blue and purple coloured fruits and vegetables (Khandelwal and Abraham, 2014a). Anthocyanidins have been reported to have ∗ Corresponding author. Present address: Department of Zoology, Dumdum Moti- jheel College, Kolkata 700074, India. Tel.: +91 9874548900 E-mail address: asmita.samadder@gmail.com (A. Samadder). antioxidant, anti-inflammatory, anticarcinogenic and antigeno- toxic activities (Khandelwal and Abraham, 2014b). Pelargonidin (PG) is one among the six most abundantly available antho- cyanidins and is known to exert antidiabetic effects in animal models (Roy et al., 2008; Mirshekar et al., 2010). These reports prompted us to examine if the antidiabetic efficacy of PG could be enhanced through its nanoencapsulation to form nano-PG (NPG) by a biodegradable environ-friendly non-toxic polymer, poly-lactide- co-glycolide (PLGA). Currently, nanoformulations of several antidiabetic drugs are used in therapeutic applications, as they offer non-toxic and effi- cient carrier system for targeted drug delivery. These nanoforms render enhanced drug bioavailability within the cells/tissues, or both (Samadder et al., 2012, 2013a,b). Information on the cura- tive properties of some phytochemicals and their nanoforms are now available. However, studies for understanding their preven- tive potential are scanty. Therefore, there is a need to evaluate the relative protective potential of nanoencapsulated phytochemicals against induced stress in suitable biological in vitro models. Interaction of phytochemicals with proteins, deoxyribonucleic acid (DNA) and other biological targets often results in modulation of key activities of cellular processes such as immune responses, signal transduction, mitosis, DNA repair mechanism, apoptosis http://dx.doi.org/10.1016/j.etap.2016.02.010 1382-6689/© 2016 Elsevier B.V. All rights reserved.