Oral administration of fumonisin B₁and T-2 individually and in combination affects hepatic total and mitochondrial membrane lipid profile of rabbits

Abstract

Weaned rabbits were fed diets contaminated with 2 mg/kg diet T-2 toxin alone, or 10 mg/kg diet fumonisin B 1 (FB 1 ) alone, and both toxins in combination (2 + 10 mg/kg, respectively) compared to a toxin-free control diet. Samplings were performed after 4 weeks (blood and liver). Bodyweight of T-2-fed group was lower after 4 weeks; the liver weight was increased dramatically (threefold of control). Liver total phospholipids (PLs) provided slight alterations in the fatty acid (FA) composition; all three toxin-treated groups showed a decrease in palmitoleic acid (C16:1 n7) proportion. In the liver mitochondrial PL FA composition, margaric acid (C17:0) proportion decreased in the separated toxin treatments compared to the combined setting. Oleic acid (C18:1 n9) proportion was increased and arachidonic acid (C20:4 n6) was decreased in the FB 1 -treated group, while docosapentaenoic acid (C22:5 n3) was decreased in the separated treatments. The total monounsaturation was significantly higher in the FB 1 group's mitochondrial PL FA profile. After 4 weeks, all toxin treatments decreased the blood plasma reduced glutathione and glutathione peroxidase activity, and FB 1 increased the plasma sphinganine/sphingosine ratio. Both mycotoxins seem to cross the hepatocellular and the hepatic mitochondrial membrane, without drastic membrane disruption, as assessed from the PL FA composition, but inducing detectable lipid peroxidation.

Identification of Signaling Pathways Targeted by the Food Contaminant FB1: Transcriptome and Kinome Analysis of Samples from Pig Liver and Intestine

“…The Sa/So ratio is a pertinent marker of exposure to FB1 in the liver, which reveals an accumulation of sphinganine due to inhibition of ceramide synthase proteins involved in ceramide de novo synthesis. Several groups have already reported an increase in this ratio in animals exposed to FB1 …”

Dose and Exposure Time-Dependent Renal and Hepatic Effects of Intraperitoneally Administered Fumonisin B1 in Rats

“…Since MDA results from end-phase lipid peroxidation, it seems that hydrogen free radicals attacked tissue lipids, as already published in an earlier study in rats [ 16 ]. Interestingly, a lower dose for a longer exposure period (10 ppm for 14 days) failed to induce MDA increment in rabbits [ 17 ], referring to a possible dose-dependent effect of FB 1 onward in vivo lipid peroxidation. It is rather interesting that initiation-phase lipid peroxidation, as assessed by the determination of conjugated dienes and trienes, was not increased in the liver by any of the treatments.…”

“…In our earlier studies, high dose (50 ppm), but short exposure (5 days) in rats depleted hepatic GSH and induced lipid peroxidation (malondialdehyde, MDA), without activating the enzymatic defense [ 16 ]. In rabbits, the hepatic lipid peroxidation was minimal, as assessed by GSH, GSHPx and MDA, after feeding 10 ppm FB 1 for 4 weeks [ 17 ]. The nature of FB 1 -induced oxidative stress is likewise acute.…”

“…The nature of FB 1 -induced oxidative stress is likewise acute. We were able to assess augmented lipid peroxidation in a short-term treatment [ 16 ], which was not present after prolonged FB 1 exposure [ 17 ]. A typical form of this adaptation has already been reported [ 18 ] where, in vitro, primary hepatocytes provided increased membrane lipid levels of C18:1 n9 (oleic acid) and reduced polyunsaturated fatty acid (PUFA) niveau, as a means to provide selective resistance to FB 1 -induced oxidative stress, and even apoptosis resistance.…”

Fumonisin B1‐induced mitochondrial toxicity and hepatoprotective potential of rooibos: An update

“…Emerging evidence also suggests that mitochondria are important molecular targets for FB 1 (Arumugam et al, 2019; Bionda, Portoukalian, Schmitt, Rodriguez‐Lafrasse, & Ardail, 2004; Domijan & Abramov, 2011). A recent study suggests that FB 1 could be rapidly absorbed by mitochondria isolated from rabbit hepatocytes without drastic membrane disruption (Szabó et al, 2016); however, changes to the normal morphology of mitochondria were observed in other studies (Ciarlo et al, 2010; Kroesen et al, 2001). Mitochondria play integral roles in energy production, calcium ions (Ca 2+ ) and redox homeostasis, as well as regulation of apoptosis.…”