Distribution of the [3H]-label from low doses of radioactive ochratoxin a ingested by rats, and evidence for DNA single-strand breaks caused in liver and kidneys

Abstract

The distribution of a single low dose of [3H]-ochratoxin A (OTA) in different tissues of male Wistar rats, after administration by intubation, was investigated after 5 h, 24 h and 48 h. This dose corresponds to concentrations encountered in naturally contaminated feed (4 ppm). The distribution of [3H]-label varied with the time elapsed after administration; at 5 h the highest specific label was found in the stomach contents and in decreasing order in: intestinal contents, lung, liver, kidney, heart, fat, intestine, testes, and the lowest in muscles, spleen and brain. With exception of brain, fat, stomach and lung, all tissues showed maximum levels at 24 h, after which time the label decreased steadily, whereas in fat it increased. After a 12-week feeding experiment, with doses of 288.8 micrograms/kg corresponding to an intake of 4 ppm in feed each 48 h, the DNA in liver and kidneys was investigated for damage. By the alkaline elution method combined with micro-spectrofluorimetric determinations of DNA, evidence for DNA single-strand breaks was obtained. These findings support reports on the carcinogenic action of OTA.

Ochratoxin A induced early hepatotoxicity: new mechanistic insights from microRNA, mRNA and proteomic profiling studies

“…Medial-dose OTA does not have impact on the serum chemical or histopathological indexes, which is consistent with OTA studies [4][5][6] . Nonetheless, the derivatives found in the liver indicates that OTA must be metabolized in order to act as a carcinogen 26 . Therefore, we selected 13 weeks as a critical time point to find out the potential candidates and their signaling cascades which may be closely associated with early liver damage.…”

Kinetic parameters and intraindividual fluctuations of ochratoxin A plasma levels in humans

“…The radioactivity found in the residue was 93% and 87%, respectively, whereas the amount of radioactivity in the water was only 2.2% and <4.5%, indicating that the largest proportion of radioactivity was associated with potential OTA metabolite(s) and/or conjugate(s), while little of the activity in the residue was tritiated water. Unfortunately, no enzymatic digestion of the water-soluble fraction with glucuronidase and/or sulphatase was carried out, thus prohibiting determination of whether the water-soluble fraction contained OTA conjugated to glucuronides or sulphates as suggested previously by Castegnaro et al (1991) and Kane et al (1986) or true OTA metabolites (phase I reaction products).…”

Ochratoxin A kinetics: A review of analytical methods and studies in rat model

“…As can be observed in table 1, the former kinetic studies (Galtier et al, 1979;Kane et al, 1986;Suzuki et al, 1977) have quantified OTA in different biological matrixes either by thin layer chromatography (TLC) or by administering radiolabelled OTA to the experimental animals. The main advantage of the aforementioned studies is that OTA has been determined in a high number of organs.…”

“…In all of the kinetic analyses performed to date with OTA, only Kane et al (1986), Suzuki et al (1977) Vettorazzi et al (2009Vettorazzi et al ( , 2011 and Han et al (2013), included control animals. As stated by the EMEA/CPMP/SWP/1094/04 Guideline, control sampling and analytical procedures should be integrated into the toxicokinetic evaluations in order to check for possible contamination between samples during the in vivo experiment or during sample preparation.…”

“…The tissue distribution of OTA in rats follows a different order, depending on the technique used to quantify OTA and the experimental design of the kinetic study (Galtier et al, 1979;Han et al, 2013;Kane et al, 1986;Li et al, 1997;Suzuki et al, 1977). Studies in rats by Chang and Chu (1977) and Suzuki et al (1977) also demonstrated accumulation of the toxin in the gastrointestinal tissues.…”