Paracetamol Overdose Induces Physiological and Pathological Aberrations in Rat Brain

Abstract

Paracetamol (Acetaminophen) is one of the most popular over the counter medications that is commonly used as an anti-inflammatory and pain killer, and to relieve fever and headaches. Despite its several therapeutic benefits, it is well known that an overdose of paracetamol can lead to hepatic and renal damage. Considering that brain cells is one of the main targets for paracetamol in the body, the effect of paracetamol on the physiology and histology of the brain is been poorly investigated. Hence, the present work investigates the possible adverse effects of paracetamol on the rat brain. Our results show that an overdose treatment of paracetamol caused significant elevation in the activity of AChE and a remarkable suppression in levels of dopamine and serotonin in treated rats. Also, applying rapid Golgi-cox staining showed that paracetamol induced morphological aberrations and a dramatic reduction in the density of dendritic spines in brain cells. Histological and ultrastructure alterations were also recorded in the neurons of paracetamol-treated rats. In conclusion, we found that an overdose of paracetamol is neurotoxic. The observed alterations point to the possibilities of higher brain impairments which is of strong public health concern.

Histological changes of CA and DG regions of hippocampus of rats’ brain after exposure to Acetaminophen in postnatal period

“…Our histological observation showed various degenerative alterations in different zones of rat hippocampus after acetaminophen treatment. These results coincided with an in vivo observations of Essawy et al who showed a harmful effect of this drug on the neurons of cerebral cortex in rats, in addition, this agent induces changes that indicate neuronal damage in granular cells of cerebral cortex (4). Acetaminophen is capable to activate the neuronal CYP2E1 thus producing toxic substances during metabolism as NAPQI (that decrease the level of glutathione and causing neurotoxicity and oxidative stress) (1), besides that, acetaminophen with overdose decreased the levels of anti-oxidants like glutathione, ascorbic acid with a relation to a significant reduction in the activity of superoxide dismutase (SOD).…”

“…Acetaminophen is capable to activate the neuronal CYP2E1 thus producing toxic substances during metabolism as NAPQI (that decrease the level of glutathione and causing neurotoxicity and oxidative stress) (1), besides that, acetaminophen with overdose decreased the levels of anti-oxidants like glutathione, ascorbic acid with a relation to a significant reduction in the activity of superoxide dismutase (SOD). The important over creation of reactive oxygen species (ROS) in brain and the imbalance between oxidative stress and antioxidants are related with pathologic alterations neurodegenerative disorders (4,(28)(29)(30).…”

“…The process of actions of acetaminophen is not clear yet, beside the fact that acetaminophen (paracetamol) is the 1 st drug to treat pain and fever throughout gestation and childhood, in addition to the increasing reports of the developmental effects, all these factors are urging for researches for its effects on neurodevelopment (1). Acetaminophen is one of the most over the counter analgesic and antipyretic agent (4). The misuses of it lead to hepatic or renal damage (5).…”

Assessment the effect of Dapoxetine and/or Acetaminophen in rats; neurochemicals and oxidative stress biomarkers evaluation

“…Paracetamol, Acetaminophen (AMP), is one the first choice over the counter medication that is frequently used as pain killer and antipyretic [9,10]. AMP can cross the blood-brain barrier with a homogenous distribution in all brain areas [11].…”

Egyptian perspectives on potential risk of paracetamol/acetaminophen-induced toxicities: Lessons learnt during COVID-19 pandemic

“…Moreover, in therapeutic intake, autophagosomes will engulf damaged mitochondria to eliminate malfunctioning mitochondria via mitophagy, reducing hepatocyte cell death. However, during paracetamol overdose, mitophagy becomes ineffective and hepatocyte cell death is enhanced due to cholesterol accumulaion in the lysosomal membrane [13] , [14] , [15] .…”