Adverse Effects of 2,4-Dichlorophenoxyacetic Acid on Rat Cerebellar Granule Cell Cultures Were Attenuated by Amphetamine

Abstract

2,4-Dichlorophenoxyacetic acid (2,4-D), a worldwide-used herbicide, has been shown to produce a wide range of adverse effects in the health--from embryotoxicity and teratogenicity to neurotoxicity--of animals and humans. In this study, neuronal morphology and biochemical events in rat cerebellar granule cell (CGC) cultures have been analyzed to define some of the possible mechanisms involved in 2,4-D-induced cell death. For that purpose, amphetamine (AMPH) that has been shown to accelerate the recovery of several functions in animals with brain injury has been used as a pharmacologycal tool and was also investigated as a possible protecting agent. Addition of 2,4-D to CGC cultures produced a drastic decrease in cell viability, in association with an increased incidence of necrosis and apoptosis, and an increased level of reactive oxygen species, a decrease in glutathione content, and an abnormal activity of some enzymes with respect to the control group. The adverse effects of 2,4-D were partly attenuated in presence of AMPH. Some deleterious effects on several ultrastructural features of the cells, as well as the enhanced incidence of apoptosis, were partially preserved in AMPH-protected cultures as compared with those which were exposed to 2,4-D alone. The collected evidences (1) confirms the previously observed, deleterious effects of 2.4D on the same or a similar model; (2) suggests that the 2,4-D-induced apoptosis could have been mediated by or associated to an oxidative imbalance in the affected cells, and (3) shows some evidence of a protective effect of AMPH on 2,4-D-induced cell death, which could have been exerted through a reduction in the oxidative stress.

A speedy recovery: amphetamines and other therapeutics that might impact the recovery from brain injury

“…Subsequently, Bongiovanni demonstrated a dosage-dependent U-shaped effect of amphetamine on cell death in rat neuronal cultures, after pretreatment no apoptotic cells could be detected in a moderate dosage of amphetamine while a high dosage resulted in an enhanced cell death. These data indicate a dosagedependent reduction in apoptosis due to a reduction in oxidative stress by the protective application of amphetamine [15,19]. In accordance, Krasnova et al [16] observed that a high dosage of methamphetamine (Table 1) resulted in DNA fragmentation and cell death in the mouse striatum and cortex.…”

“…Investigating the effects of amphetamine on the cellular level, Bongiovanni and colleagues [15] first induced cell toxicity and apoptosis in rat cerebellar granule cell cultures. Subsequently, Bongiovanni demonstrated a dosage-dependent U-shaped effect of amphetamine on cell death in rat neuronal cultures, after pretreatment no apoptotic cells could be detected in a moderate dosage of amphetamine while a high dosage resulted in an enhanced cell death.…”

Extra virgin olive oil modulates brain docosahexaenoic acid level and oxidative damage caused by 2,4-Dichlorophenoxyacetic acid in rats

“…The central nervous system (CNS) is mainly susceptible to oxidative stress. This is mainly due to its high amounts of polyunsaturated fatty acids (PUFA) content which constitutes easily-oxidizable substrates and an inherently high flux of reactive oxygen species (ROS) (Bongiovanni et al 2007(Bongiovanni et al , 2011. Another reason of oxidative stress is the low level of endogenous antioxidant enzymes in CNS relative to other tissues, and its high oxygen consumption (Somani et al 1996).…”

“…In fact, under physiological O 2 levels, 1-2 % of the O 2 consumed is converted to ROS mostly through the mitochondrial respiratory chain (Emerit et al 2004). Therefore, the CNS is potentially sensitive to oxidative damage (Bongiovanni et al 2007(Bongiovanni et al , 2011 which may play a role in dementia and age-associated neurodegenerative diseases such as Alzheimer's disease (Behl 1999;Pratico and Delanty 2000).…”

Determination of acidic herbicides in water samples by in situ derivatization, single drop microextraction and gas chromatography-mass spectrometry

“…Due to their biological activity, their determination in aqueous samples is important. [6][7][8] Suitable methods exist for quantitative measurement of acidic herbicides in water samples, using gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography-mass spectrometry (HPLC-MS), but in general the preconcentration step is extensive, requiring large sample volumes (between 0.5 and 2.0 L), sample clean-up or the use of organic solvents. [9][10][11][12][13][14] There is a need for fast and simple methods to supply this analysis.…”