Zebrafish (Danio rerio) ability to activate ABCC transporters after exposure to glyphosate and its formulation Roundup Transorb®.

The emergent demand for food production has increased the widespread use of pesticides, especially glyphosate-based herbicides as they can protect different types of crops, especially transgenic ones. Molecules of glyphosate have been found in water bodies around the world, and its presence can cause negative effects on non-target organisms, such as fish. Glyphosate toxicity appears to be systemic in fish but does not affect their organs equally. Also, its formulations can be more toxic than pure glyphosate. In this sense, we investigated if these variations in toxicity could be related to ATP binding cassette subfamily C (ABCC) transporters and the cellular detoxification capacity, following exposure to herbicides. Thus, adults of Danio rerio were exposed (24 and 96 h) to glyphosate and Roundup Transorb® (RT) at an environmental concentration of 0.1 mg/L, and the activity of ABCC proteins and gene expression of five isoforms of ABCC were analyzed. Glyphosate and RT exposure increased ABCC protein activity and gene expression up to 3-fold when compared to controls, indicating the activation of detoxification mechanisms. Only in the brain of D. rerio, the exposure to RT did not stimulate the activity of ABCC proteins, neither the expression of genes abcc1 and abcc4 that responded to the exposure to pure glyphosate. These results may suggest that the brain is more sensitive to RT than the other target-tissues since the mechanism of detoxification via ABCC transporters were not activated in this tissue as it was in the other.

Protective role of the novel hybrid 3,5-dipalmitoyl-nifedipine in a cardiomyoblast culture subjected to simulated ischemia/reperfusion.

This work investigated the acute effects of the calcium channel blocker nifedipine and its new fatty hybrid derived from palmitic acid, 3,5-dipalmitoyl-nifedipine, compared to endocannabinoid anandamide during the process of inducing ischemia and reperfusion in cardiomyoblast H9c2 heart cells. The cardiomyoblasts were treated in 24 or 96-well plates (according to the test being performed) and maintaining the treatment until the end of hypoxia induction. The molecules were tested at concentrations of 10 and 100µM, cells were treated 24h after assembling the experimental plates and immediately before the I/R. Cell viability, apoptosis and necrosis, and generation of reactive oxygen species were evaluated. Nifedipine and 3,5-dipalmitoyl-nifedipine were used to assess radical scavenging potential and metal chelation. All tested molecules managed to reduce the levels of reactive oxygen species compared to the starvation+vehicle group. In in vitro assays, 3,5-dipalmitoyl-nifedipine showed more antioxidant activity than nifedipine. These results indicate the ability of this molecule to act as a powerful ROS scavenger. Cell viability was highest when cells were induced to I/R by both concentrations of anandamide and the higher concentration of DPN. These treatments also reduced cell death. Therefore, it was demonstrated that the process of hybridization of nifedipine with two palmitic acid chains assigns a greater cardioprotective effect to this molecule, thereby reducing the damage caused by hypoxia and reoxygenation in cardiomyoblast cultures.