The diabetogenic effects of the combination of humic acid and arsenic: in vitro and in vivo studies.
Black foot disease (BFD) is a peripheral arterial occlusive disease found among the inhabitants of the southwest coast of Taiwan. Moreover, within the BFD-endemic areas, diabetes mellitus occur at significantly higher rates than in other areas of Taiwan. A high concentration of humic acid (HA), and arsenic (As) are present in the artesian well water from BFD-endemic area. The aim of this paper is to study the diabetogenic effect of the combination of HA and AS. Treatment of HIT-T15 cells with HA, As, or both of them resulted loss of cell viability, apoptosis, depletion of ATP, increment of oxidative stress, activation of caspase 3, and dysfunction of insulin secretion. In addition, the plasma insulin of ICR mice, which were exposed to HA and As in drinking water for 12 weeks, was decreased in the 5, 7, and 12 weeks, and increased at early stage of exposure (3 weeks). The results reported herein reveal that HA and As exert HIT-T15 cell dysfunction and inhibited insulin secretive effects. In addition, the sub-acute peri-pancreatitis and islet damage caused by the infiltration of inflammatory cells after exposure of HA and As in drinking water for 5 weeks. Our study has important implications in the diabetogenic effect of the HA and AS which may be mediated by ROS and further information of the toxicity mechanisms will provide under our progressive studies.
Yen
Cheng-Chieh
CC
Department of Occupational Safety and Health, College of Health Care and Management, Chung Shan Medical University, Taichung, Taiwan. ycj@csmu.edu.tw
Lu
Fung-Jou
FJ
Huang
Chun-Fa
CF
Chen
Wen-Kang
WK
Liu
Shing-Hwa
SH
Lin-Shiau
Shoei-Yn
SY
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001151:Arsenic / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D006812:Humic Substances / Q000633:toxicity*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D006812:Humic Substances; D007328:Insulin; D017382:Reactive Oxygen Species; D014874:Water Pollutants, Chemical; D000255:Adenosine Triphosphate; D053148:Caspase 3; D005978:Glutathione; D001151:Arsenic