Significant Biotransformation of Arsenobetaine into Inorganic Arsenic in Mice

Abstract

Arsenic (As) is extremely toxic to living organisms at high concentrations. Arsenobetaine (AsB), confirmed to be a non-toxic form, is the main contributor to As in the muscle tissue of marine fish. However, few studies have investigated the biotransformation and biodegradation of AsB in mammals. In the current study, C57BL/6J mice were fed four different diets, namely, Yangjiang and Zhanjiang fish diets spiked with marine fish muscle containing AsB, and arsenite (As(III)) and arsenate (As(V)) diets spiked with As(III) and As(V), respectively, to investigate the biotransformation and bioaccumulation of AsB in mouse tissues for 42 d. Different diets exhibited different As species distributions, which contributed to varying levels of As bioaccumulation in different tissues. The intestines accumulated the highest level of As, regardless of form, which played a major part in As absorption and distribution in mice. We observed a significant biotransformation of AsB to As(V) following its diet exposure, and the liver, lungs, and spleen of AsB-treated mice showed higher As accumulation levels than those of As(III)- or As(V)-treated mice. Inorganic As showed relatively high accumulation levels in the lungs and spleen after long-term exposure to AsB. Overall, these findings provided strong evidence that AsB undergoes biotransformation to As(V) in mammals, indicating the potential health risk associated with long-term AsB intake in mammals.

Microbiota-dependent in vivo biotransformation, accumulation, and excretion of arsenic from arsenobetaine-rich diet

“…Although early toxicokinetic human studies concluded that urinary excretion of seafood-derived AB is fast and efficient [44][45][46][47], later work indicated that intestinal absorption and urinary excretion of AB from seafood diet may not always be efficient [48][49][50]. Recent studies have reported gut-microbiota dependent AB accumulation in mice [51] and hypothesized that under chronic exposure scenarios and depending on the specific AB-containing food matrix, a significant portion of AB may reach the large intestinal lumen, where microbial AB degradation can occur, potentially producing arsenic species of health concern [52]. However, these studies did not definitively establish the causal role of intestinal bacteria in these processes.…”

Transformation of arsenic species from seafood consumption during in vitro digestion

“…After oral intake, these chemicals are transferred to the gastrointestinal tract; however, only a proportion of them can be absorbed by the human body and cause toxic effects. Information on the real absorption of different As species in the human gastrointestinal tract is very limited, but according to some studies with mice, AsB has a significantly higher absorption efficiency (over 96%) than As(III) and As(V) (approximately 81 and 86%, respectively), and significant biotransformation of AsB to [As(V)] following oral administration has been indicated (10). Therefore, fully considering bio-accessibility (the proportion of these chemicals that have undergone possible biotransformation during digestion and can be released from the food matrix for human body absorption) in toxicity evaluation seems to be more accurate than just analyzing the undigested food sample itself.…”