Pathological, immunological and biochemical markers of subchronic arsenic toxicity in rats

Abstract

Subchronic exposure to arsenic in rats was investigated to identify sensitive indicators of subclinical toxicity in rats. Immunological, pathological, and biochemical bioindicators were examined in rats exposed to arsenic in their drinking water. Juvenile male Wistar rats were allocated to four treatment groups receiving 0, 0.4, 4, and 40 ppm of arsenite in drinking water for 18 wks. Besides daily monitoring for clinical signs of adverse health effects, clinical biochemistry, B-cell-mediated and innate immune responses, plus gross, and histopathology were examined. In vitro tests of oxidative damage to basic cellular constituents, lipids, proteins, and nucleic acids, were measured using thiobarbituric acid reacting substances (TBARS) assays, protein carbonyl formation, and 8-hydroxydeoxyguanosine (8-OHdG), respectively. Clinical changes in the rats were limited to decreased feed and water intake in the high- (40 ppm) dose group (P < 0.05), however, growth rate was not affected. Serum biochemical changes occurred in blood urea nitrogen, K(+) , Cl(-) , and alanine aminotransferase (ALT) from arsenic exposure. Immunotoxicity was evident through a dose-dependent suppression of the secondary antibody-mediated response to a T-cell-dependent antigen, keyhole limpet hemocyanin (KLH). Histopathology of the liver revealed marked fatty infiltration and vacuolization particularly evident in periacinar hepatocytes. This pattern of toxicopathology in the high-exposure group may be related to the significantly higher (P < 0.05) oxidative stress, demonstrated through lipid peroxidation (TBARS assay) in the rats exposed to 40 ppm arsenite. The present study revealed that young, growing rats exposed to arsenic for 18 wks tolerated exposures up to 4 ppm. At higher doses, there was evidence of hepatotoxicity, humoral immunity was compromised, and an adverse effect on hepatic organelle and cell membranes was evident through a dose dependent increased in oxidative stress.

Aqueous Extract of Carica Papaya Linn Roots Halts Sodium Arsenite-Induced Renal Inflammation through Inhibiting Adenosine Deaminase, 8-Hydroxy-2′-Deoxyguanosine, C-Reactive Protein and Inducible Nitric Oxide Synthase Activity

“…8-OHdG, may be a novel biomarker for arsenic-induced renal inflammation and oxidative stress. It was reported that elevated levels of 8-OHdG in plasma will cause DNA damage in arsenic exposed rats (26). In this study, levels of 8-OHdG in plasma from arsenic only treated rats were significantly increased compared to control rats, which is similar to the reports of (26).…”

“…It was reported that elevated levels of 8-OHdG in plasma will cause DNA damage in arsenic exposed rats (26). In this study, levels of 8-OHdG in plasma from arsenic only treated rats were significantly increased compared to control rats, which is similar to the reports of (26). Increased levels of 8-OHdG could also be as a result of oxidative stress induced by the arsenic (27).…”

Dietary selenium fortification: a potential solution to chronic arsenic toxicity

“…In a previous study challenging rats with 0.4, 4, and 40 ppm As in drinking water, only 40 ppm arsenite produced any clinical or subclinical evidence of toxicity (Nain and Smits 2010). To investigate the potential advantages of Se as an As antagonist, two challenge levels of As based on known exposures of humans (Mandal and Suzuki 2002;Spallholz, Boylan, and Rhaman 2004) and on the previous study, were selected to identify Asinduced changes (Nain and Smits 2010) and response to dietary selenium.…”

“…To investigate the potential advantages of Se as an As antagonist, two challenge levels of As based on known exposures of humans (Mandal and Suzuki 2002;Spallholz, Boylan, and Rhaman 2004) and on the previous study, were selected to identify Asinduced changes (Nain and Smits 2010) and response to dietary selenium.…”

Immunosuppressive effects of arsenic in broiler chicks exposed to Newcastle disease virus

“…Arsenic, both in vivo and in vitro, also acts as an immunosuppressive to impair the function of several key immune cells (Martin-Chouly et al 2011). As a result, general decreases in cellular and humoral immune response have been documented; in one specific case, the number of splenic antibody-forming cells generated against a T-dependent antigen (like sheep erythrocytes) was decreased (Nain & Smits 2012).…”