title: Nanopharmaceutical approach using pelargonidin towards enhancement of efficacy for prevention of alloxan-induced DNA damage in L6 cells via activation of PARP and p53.
abstract: Alloxan is an environmental food contaminant that causes DNA damage in living cells and induces hyperglycemia. 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 prevention 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 activating DNA repair cascades. Results suggested ∼10-fold increase in efficacy of NPG than PG in prevention of alloxan-induced oxidative stress and DNA damage.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: asmita.samadder@gmail.com.
authors.forename: Asmita
authors.initials: A
authors.lastname: Samadder
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Abraham
authors.affiliation: Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India.
authors.forename: Anisur Rahman
authors.initials: AR
authors.lastname: Khuda-Bukhsh
mesh_terms: D000496:Alloxan / Q000633:toxicity; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects; D006943:Hyperglycemia; D053758:Nanoparticles; D018384:Oxidative Stress / Q000187:drug effects*; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000872:Anthocyanins; D020011:Protective Agents; D016159:Tumor Suppressor Protein p53; D000496:Alloxan; C066957:pelargonidin; D000071137:Poly (ADP-Ribose) Polymerase-1
keywords: Alloxan; DNA repair cascade; DNA stability curve; L6 cell line; PLGA encapsulation; Pelargonidin