title: Future of nano bisdemethoxy curcumin analog: guaranteeing safer intravenous delivery.
abstract: The present study deals with the toxicity assessment of NBDMCA in vitro using red cell model and in vivo using rat model. Hemolysis was used as toxicity index in red blood cells. Different concentrations of NBDMCA viz., 20, 40, 60, 80, 100μg/ml in PBS were incubated with the red blood cells of rat. NBDMCA was found to induce less than 3% hemolysis in intact erythrocytes which was far lesser than the accepted threshold of 5%. Hematological cum biochemical parameters along with histopathological analysis and hemolysis were used as toxicity indices in rats. Whole blood of the NBDMCA-treated rats and control rats were analyzed for hematological parameters: erythrocyte count, leukocyte count, leukocyte differential count, hemoglobin, hematocrit, mean cell volume (MCV), mean corpuscular hemoglobin (MCH) using fully automated hematology analyzer. All hematological parameters analyzed were within the normal values in both the groups. Plasma samples were analyzed for biochemical parameters including glucose, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine (Cre), albumin (Alb), total protein (TP), calcium (Ca) and phosphorus (P) using fully automated biochemistry analyzer. Invariably, all the biochemical parameters are significantly similar in both the groups. Gross examination of vital organs like lung, heart, kidney, spleen and brain reveals no detectable abnormalities in NBDMCA-treated animals. Internal organs like heart, brain, lung, liver, spleen and kidneys of the experimental animals were collected and fixed in 10% formalin, processed in vacuum infiltration tissue processor, embedded with paraffin wax and sectioned at approximately 5μm thick, stained with hematoxylin and eosin. The sections were examined and imaged through light microscopy. NBDMCA did not produce any significant changes in the histoarchitecture of all the organs studied. Heart, aorta, brain, lung, liver, kidney and spleen showed normal pathology report. The histopathological data correlated with the biochemical results indicating normal hepatocellular and nephrotic function. Our investigation clearly revealed that NBDMCA is hemocompatible in vitro and also safe to vital organs in vivo. We conclude that NBDMCA is non-toxic and safe and can be promoted as an ideal therapeutic tool for human use.
authors.affiliation: Centre for Nanoscience and Technology, A.C. Tech Campus, Anna University, Tamil Nadu, India.
authors.forename: Arul Prakash
authors.initials: AP
authors.lastname: Francis
authors.affiliation: International Institute of Biotechnology and Toxicology (IIBAT), Padappai, India.
authors.forename: Selvam
authors.initials: S
authors.lastname: Ganapathy
authors.affiliation: International Institute of Biotechnology and Toxicology (IIBAT), Padappai, India.
authors.forename: Venkata Rajsekhar
authors.initials: VR
authors.lastname: Palla
authors.affiliation: International Institute of Biotechnology and Toxicology (IIBAT), Padappai, India.
authors.forename: Prakhya Balakrishna
authors.initials: PB
authors.lastname: Murthy
authors.affiliation: Centre for Nanoscience and Technology, A.C. Tech Campus, Anna University, Tamil Nadu, India. Electronic address: tdevasenabio@annauniv.edu.
authors.forename: Thiyagarajan
authors.initials: T
authors.lastname: Devasena
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D002478:Cells, Cultured; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D036381:Diarylheptanoids; D004906:Erythrocyte Count; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D007958:Leukocyte Count; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D017208:Rats, Wistar
chemical_list: D036381:Diarylheptanoids; C034786:bisdemethoxycurcumin; D003474:Curcumin
keywords: Intravenous; NBDMCA; Nanoparticles; Safety; Toxicity