Ph ton 487 The Journal of Toxicology and Health. Photon 105(2014) 487-493 https://sites.google.com/site/photonfoundationorganization/home/the-journal-of-toxicology-and-health Original Research Article. ISJN: 2294-7439: Impact Index: 4.72 The Journal of Toxicology and Health Ph ton Arsenic toxicity in pancreas of diabetic rats Neetu Singh, S.V.S. Rana Toxicology Laboratory, Department of Zoology, Ch. Charan Singh University, Meerut, India–250 004 Neetu Singh, S.V.S. Rana receive International Toxicology Research Award-2014 Article history: Received: 17 June, 2014 Accepted: 22 June, 2014 Available online: 09 December, 2014 Keywords: Arsenic trioxide (As2O3), pancreas, diabetes mellitus, insulin, rat Corresponding Author: S.V.S. Rana* Professor Email: sureshvs_rana@yahoo.com, sureshvs.rana@gmail.com Neetu Singh Research Assistant Abstract Toxicity of arsenic trioxide (As III ) in exocrine and endocrine pancreas of rat has been addressed in this communication. Experimental diabetes was induced in rats through alloxen monohydrate (12.5 mg/100g). Arsenic trioxide was administered to diabetic rats (4 mg/100g) on each alternate day for 30 day. Thereafter, observations on accumulation of iAs in pancreas, insulin, liver, and histopathological studies were made. Results show that inorganic arsenic (iAs) is cumulative in pancreas. Further it damages β-cells and affect insulin secretion. In alloxan induced diabetic rats, accumulation of iAs in pancreas is diminished but no improvement in insulin concentration is noticed. Histopathological observations showed atrophy in the acinar tissue and insulitis in the islets. Further, pycnosis and apoptosis were recorded in arsenic treated diabetic rats. Ultrastructural observations reveal increased number of condensed vacuoles in the pancreas of iAs treated rats. Proliferation of zymogen granules was witnessed in arsenic treated diabetic rats. It is concluded that pancreas is also a suitable target organ for arsenic. Further, diabetes mellitus changes the toxico-kinetics of arsenic in rat. Citation: Singh N., Rana S.V.S., 2014. Arsenic toxicity in pancreas of diabetic rats. The Journal of Toxicology and Health. Photon 105, 487-493. All Rights Reserved with Photon. Photon Ignitor: ISJN22947439D720709122014 1. Introduction Arsenic is an established environmental poison (Hughes et al., 2007; IARC, 2004; NRC, 1999). It affects numerous systemic functions and organs, viz. nervous system, hematopoietic system, liver, kidneys and skin (Blom et al., 1985). Chronic arsenic exposure has also been reported as a potential risk factor for type II diabetes (Rahaman et al., 1998; Rahaman and Axelson, 1995). It is a metabolic disorder characterized by hyperglycaemia, insulin resistance in peripheral tissues, and altered insulin secretory capacity of pancreatic β cells (Kahn et al., 1993; Kahn, 2003). Several studies in different ethnic groups during different study periods have shown an association between arsenic exposure and the occurrence of diabetes mellitus (Chen et al., 2007; Navas-Acien, 2008). Effects of arsenic on glucose metabolism have been attributed to its reactivity towards thiol (SH) groups (Aposhian et al., 1989; NRC, 1999). During acute poisoning, arsenite inhibits pyruvate and α-ketoglutarate dehydrogenases, the essential enzymes for gluconeogenesis and glycolysis (Aposhian et al., 1989). A recent report from our laboratory showed that iAs when administered to alloxan diabetic rats improved their liver function (Singh and Rana, 2009). Further, convincing reports show that diabetes alters the pharmoco-dynamics and pharmaco-kinetics of drugs/xenobiotics in man and animals (Chawalit et al., 1982; Longhurst et al., 1986). Therefore, it could modulate its toxic manifestations. An earlier report from our laboratory also indicated such involvement in liver (Singh and Rana, 2009). The aim of the present study was to demonstrate the