Effect of feeding graded doses of citrinin on apoptosis and oxidative stress in male Wistar rats through the F₁ generation

Abstract

The objective of the present study was to study the effect of graded doses of citrinin (CIT) on apoptosis and oxidative stress in male Wistar rats till F1 generation. The animals were divided into four groups comprising 25 males and 25 females each, that is, group I: 1 ppm CIT; group II: 3 ppm CIT; group III: 5 ppm CIT; and group IV was kept as a control. The male and female animals of all the groups were kept separately and were fed basal rations containing the above-mentioned concentrations of CIT for 10 weeks. After 10 weeks, male and female animals of respective groups were kept for mating (one male/two females). After getting 10 pregnant females, the males were killed. These 10 pregnant females were allowed to give birth to young ones (F1 generation) naturally which were fed CIT in the above-mentioned doses till the age of 6 weeks and then were killed. Apoptosis was analysed in kidneys, liver and testes by DNA ladder pattern, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end-labelling assay and Bcl-2/Bax ratio. Besides, tissue oxidative stress was also analysed. It was concluded in the present study that CIT induces its toxic effects till F1 generation, and apoptosis and oxidative stress both play a very important role in toxicity. The effect of CIT was observed in a dose-dependent manner. However, in kidneys, both the mechanisms (apoptosis and oxidative stress) play their role in inflicting renal damage, while in liver only reactive oxygen species play a major role. Finally, the CIT toxicity did not lead to apoptosis and oxidative stress in male gonads till F1 generation.

Different Toxicity Mechanisms for Citrinin and Ochratoxin A Revealed by Transcriptomic Analysis in Yeast

“…Moreover, oxidative stress reporters are immediately upregulated upon CIT exposure and yeast mutants with a weakened antioxidant defense are hypersensitive to this mycotoxin, which altogether suggests that the induction of ROS inside cells is a primary mode of CIT action. Our result is in agreement with a previous transcriptomic assay in yeast upon prolonged CIT treatment [41] and with several studies showing CIT induced oxidative damage in diverse cellular models from yeast to humans [26,27,28,30]. As a consequence, external addition of antioxidants usually alleviates CIT toxicity [25,48,49].…”

“…Much less is known about the toxicity mechanisms of CIT, however, it has been shown to be an efficient nephrotoxin as well [22]. Several groups have contributed to the identification of possible molecular mechanisms of CIT toxicity, finding, among other consequences, the increase of oxidative stress in connection with alterations of mitochondrial function, and induction of apoptosis [23,24,25,26,27,28,29,30,31]. It has been proposed that the co-occurrence of both toxins results in synergetic effects, however no clear conclusions have been reached [32,33].…”

Hepatotoxic effect of ochratoxin A and citrinin, alone and in combination, and protective effect of vitamin E: In vitro study in HepG2 cell

“…ROS play a major role in CTN-induced hepatotoxicity in Wistar rat (Singh et al, 2013). On the other hand in mouse skin (Kumar et al, 2011), HepG2 (Chen and Chan, 2009) and HL-60 (Yu et al, 2006) cells CTN induces ROS-mediated mitochondria-dependent apoptosis.…”

Toxicity Mechanisms of the Food Contaminant Citrinin: Application of a Quantitative Yeast Model

“…Although the actual mechanism of citrinin toxicity is not entirely understood, in many toxicological models it has been found to cause nephrotoxicity [ 4 ]. Several studies in different cell systems seem to confirm that citrinin can generally cause the production of reactive oxygen species (ROS) [ 5 , 6 , 7 , 8 , 9 ]. Moreover, antioxidants have been shown to alleviate the citrinin toxicity [ 10 , 11 ].…”