Paracetamol − Effect of early exposure on neurotransmission, spatial memory and motor performance in rats

Blecharz-Klin, Kamilla; Piechal, Agnieszka; Jawna-Zboińska, Katarzyna; Pyrzanowska, Justyna; Wawer, Adriana; Joniec-Maciejak, Ilona; Widy-Tyszkiewicz, Ewa

doi:10.1016/j.bbr.2017.01.051

Cited by 34 publications

(24 citation statements)

References 37 publications

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“…Two additional papers were excluded after reading the full paper version (in both because paracetamol was not used in these studies, but mentioned in the abstract), and one additional paper was included following citation verification to result in 20 papers (Prisma flowchart, Figure 1). Table I provides an overview on the quality assessment (SYRCLE's risk of bias tool) results [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]. This reflects a heterogeneous pattern with mainly issues related to blinding (for performance, for detection) procedures in a relevant portion of the studies (unclear or unreported, high risk in 16/20 for both) and allocation concealment (was the method used to conceal the allocation sequence described in sufficient detail to determine whether intervention allocation could have been foreseen before or during enrolment?).…”

Section: Resultsmentioning

confidence: 99%

How to translate neuro-cognitive and behavioural outcome data in animals exposed to paracetamol to the human perinatal setting?

Allegaert

Anker

2020

Arch Med Sci

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IntroductionIntroduction: There are epidemiological – not necessary causal – observations that link perinatal paracetamol (acetaminophen) exposure to impaired neuro-cognition and behaviour, but animal models may assist to better understand the mechanisms.Material and methodsTo provide an overview on preclinical data and mechanisms explored, we conducted a structured literature search on animal models and neuro-cognition and behavioural outcome following perinatal paracetamol exposure.ResultsThis search resulted in 20 papers [rat (n = 9), zebrafish larvae (n = 6), mice (n = 5)], published between 2009 and 2020. Eight discussed pregnancy/fetal paracetamol exposure, 6 juvenile, 6 studies combined pregnancy and juvenile exposure. Quality assessment (SYRCLE’s bias risk) showed a heterogeneous pattern with blinding issues. Most papers (n = 16) described paracetamol exposure without indication, except for an induced fever and repetitive needle pricking (rat), brain injury (mice), and a zebrafish nociception model. Reported outcomes related to biochemistry (mono-amines, amino acids, protein expression), anatomy (teratogen, morphology, nuclear size) or behaviour (spatial memory, motor, social behaviour and exploration, sexual behaviour). On mechanisms, the cumulative data support an interesting ‘cannabinoid’ hypothesis to link paracetamol to neuro-cognitive and behavioural outcome. Besides limited species diversity, there is relevant within-species paracetamol dosing variability (dose, duration) with undocumented exposure.ConclusionsModels should further integrate clinical indications, as non-exposure is the obvious safest setting in the absence of an indication. Besides pain and fever and related to the cannabinoid hypothesis, this should include perinatal brain injury, as there is animal experimental evidence that cannabinoids are neuroprotective in newborn brain injury or asphyxia, further supported by evidence from non-perinatal models of paracetamol-related neuroprotective effects.

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Section: Resultsmentioning

confidence: 99%

How to translate neuro-cognitive and behavioural outcome data in animals exposed to paracetamol to the human perinatal setting?

Allegaert

Anker

2020

Arch Med Sci

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“…After paracetamol exposure, the concentration and metabolism of many neurotransmitters is changed. The most important changes concern the striatum and other structures involved in the planning, coordination, social behaviour and motor skills (Blecharz‐Klin et al, 2017, 2018).…”

Section: Discussionmentioning

confidence: 99%

Hypothalamus – Response to early paracetamol exposure in male rats offspring

Blecharz-Klin

Wawer

Pyrzanowska

et al. 2019

Intl J of Devlp Neuroscience

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One of the reasons for using paracetamol during pregnancy is fever. The brain structure responsible for maintaining proper body temperature, but also for controlling some endocrine aspects is hypothalamus. In this study we examined the effect of early pretreatment of paracetamol on hypothalamic neurotransmission in rats' offspring. We used two‐month old rats previously exposed to paracetamol at doses of 5 (P5) and 15 mg/kg (P15) during gestational development and next postnatally. The concentration of monoamines, their metabolites and amino acids in hypothalamus was chromatographically determined. The results of biochemical analysis were compared with the Control animals (Con). We found differences between groups in the concentration of main noradrenaline metabolite in hypothalamus. The control group had significantly higher level of 3‐methoxy‐4‐hydroxyphenylglycol (MHPG) compared with rats exposed to paracetamol (F(2,27) = 7.96, p < 0.005). Simultaneously the level of dopamine (DA) (F(2,27) = 4.33, p < 0.05) and its metabolite ‐ homovanillic acid (HVA) (F(2,27) = 17.03, p < 0.005) was increased in the hypothalamus of animals treated with lower dose of the drug. Biochemical analyses show an increase in 3,4‐dihydroxyphenyl acetic acid (DOPAC) concentration in P5 group compared to the control rats and group treated with higher dose of paracetamol (F(2,27) = 7.37, p < 0.005). In the hypothalamus significant decrease of glutamic acid concentration was also observed in the group treated with paracetamol at dose of 5 mg. These results demonstrated that paracetamol had a significant effect on dopaminergic and noradrenergic neurotransmission and changed the concentration of glutamic acid in hypothalamus ‐ heat‐regulating center and important element of hypothalamic‐pituitary‐ gonadal axis.

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“…The body weight was checked each week and allowed for adjustment of the dihydroergotamine dose. Animals were housed 2 per cage in a room with a 12 h dark-light cycle, constant temperature of 24-26 °C and humidity at about 60% [23]. The rats received standard chow (Labofeed, Kcynia, Poland).…”

Section: Methodsmentioning

confidence: 99%

Dihydroergotamine affects spatial behavior and neurotransmission in the central nervous system of Wistar rats

Piechal¹,

Blecharz-Klin²,

Joniec-Maciejak³

et al. 2021

Ann Agric Environ Med.

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Paracetamol − Effect of early exposure on neurotransmission, spatial memory and motor performance in rats

Cited by 34 publications

References 37 publications

How to translate neuro-cognitive and behavioural outcome data in animals exposed to paracetamol to the human perinatal setting?

How to translate neuro-cognitive and behavioural outcome data in animals exposed to paracetamol to the human perinatal setting?

Hypothalamus – Response to early paracetamol exposure in male rats offspring

Dihydroergotamine affects spatial behavior and neurotransmission in the central nervous system of Wistar rats

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