Effects of the Analgesic Acetaminophen (Paracetamol) and its para‐Aminophenol Metabolite on Viability of Mouse‐Cultured Cortical Neurons

Schultz, Stanley G.; DeSilva, Mauris N.; Gu, Tao; Mei, Qiang; Whang, Kyumin

doi:10.1111/j.1742-7843.2011.00767.x

Cited by 23 publications

(15 citation statements)

References 18 publications

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“…An interesting theory relating the MMR vaccine to ASD involves a proposed toxic reaction to the acetaminophen (paracetamol) administered to control fever following vaccination [25,106]. It has been proposed that acetaminophen may mediate oxidative stress and neurotoxicity in autism [107], and acetaminophen has been demonstrated to be toxic to developing mouse cortical neurons in vitro [108]. Table 2.…”

Section: Distribution Of Vaccine Types In Autism Versus Controlsmentioning

confidence: 99%

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Seneff

Davidson²,

Liu

2012

Entropy

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Autism is a condition characterized by impaired cognitive and social skills, associated with compromised immune function. The incidence is alarmingly on the rise, and environmental factors are increasingly suspected to play a role. This paper investigates word frequency patterns in the U.S. CDC Vaccine Adverse Events Reporting System (VAERS) database. Our results provide strong evidence supporting a link between autism and the aluminum in vaccines. A literature review showing toxicity of aluminum in human physiology offers further support. Mentions of autism in VAERS increased steadily at the end of the last century, during a period when mercury was being phased out, while aluminum adjuvant burden was being increased. Using standard log-likelihood ratio techniques, we identify several signs and symptoms that are significantly more prevalent in vaccine reports after 2000, including cellulitis, seizure, depression, fatigue, pain and death, which are also significantly associated with aluminum-containing vaccines. We propose that children with the autism diagnosis are especially vulnerable to toxic metals such as aluminum and mercury due to insufficient serum sulfate and glutathione. A strong correlation between autism and the MMR (Measles, Mumps, Rubella) vaccine is also observed, which may be partially explained via an increased sensitivity to acetaminophen administered to control fever.

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Section: Distribution Of Vaccine Types In Autism Versus Controlsmentioning

confidence: 99%

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Seneff

Davidson²,

Liu

2012

Entropy

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“…P-aminophenol is recognized to be involved in paracetamol nephrotoxicity [81,109]. More recently, P-aminophenol has been shown to produce a significant loss in mouse cortical neuron viability at therapeutic concentrations [12]. This suggests another possible pathway for a neurotoxic effect of paracetamol when the principle metabolic routes are exhausted.…”

Section: Discussionmentioning

confidence: 99%

“…A recent investigation found transcriptomic changes in full-genome human miRNA expression indicating, for the first time, immune modulating effects and oxidative stress responses to paracetamol even at low doses [10]. Studies in animals have shown paracetamol to induce apoptosis and neurotoxicity [11,12]. Several studies hypothesize increased apoptosis in the autistic brain [13-16].…”

Section: Introductionmentioning

confidence: 99%

Prenatal and perinatal analgesic exposure and autism: an ecological link

2013

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BackgroundAutism and Autism Spectrum Disorder (ASD) are complex neurodevelopmental disorders. Susceptibility is believed to be the interaction of genetic heritability and environmental factors. The synchronous rises in autism/ASD prevalence and paracetamol (acetaminophen) use, as well as biologic plausibility have led to the hypothesis that paracetamol exposure may increase autism/ASD risk.MethodsTo explore the relationship of antenatal paracetamol exposure to ASD, population weighted average autism prevalence rates and paracetamol usage rates were compared. To explore the relationship of early neonatal paracetamol exposure to autism/ASD, population weighted average male autism prevalence rates for all available countries and U.S. states were compared to male circumcision rates – a procedure for which paracetamol has been widely prescribed since the mid-1990s. Prevalence studies were extracted from the U.S. Centers for Disease Control and Prevention Summary of Autism/ASD Prevalence Studies database. Maternal paracetamol usage and circumcision rates were identified by searches on Pub Med.ResultsUsing all available country-level data (n = 8) for the period 1984 to 2005, prenatal use of paracetamol was correlated with autism/ASD prevalence (r = 0.80). For studies including boys born after 1995, there was a strong correlation between country-level (n = 9) autism/ASD prevalence in males and a country’s circumcision rate (r = 0.98). A very similar pattern was seen among U.S. states and when comparing the 3 main racial/ethnic groups in the U.S. The country-level correlation between autism/ASD prevalence in males and paracetamol was considerably weaker before 1995 when the drug became widely used during circumcision.ConclusionsThis ecological analysis identified country-level correlations between indicators of prenatal and perinatal paracetamol exposure and autism/ASD. State level correlation was also identified for the indicator of perinatal paracetamol exposure and autism/ASD. Like all ecological analyses, these data cannot provide strong evidence of causality. However, biologic plausibility is provided by a growing body of experimental and clinical evidence linking paracetamol metabolism to pathways shown to be important in autism and related developmental abnormalities. Taken together, these ecological findings and mechanistic evidence suggest the need for formal study of the role of paracetamol in autism.

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“…While there are data from pharmacokinetics studies [12,13], the pharmacodynamics of paracetamol in neonates are poorly described. Allegaert et al [14] showed a reduction of pain after 20 mg/kg of paracetamol in preterm and term infants suffering from delivery trauma.…”

Section: Discussionmentioning

confidence: 99%

Randomized Controlled Trial Comparing Different Single Doses of Intravenous Paracetamol for Placement of Peripherally Inserted Central Catheters in Preterm Infants

et al. 2017

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Background: The availability of a safe and effective pharmacological therapy to reduce procedural pain in preterm infants is limited. The effective analgesic single dose of intravenous paracetamol in preterm infants is unknown. Comparative studies on efficacy of different paracetamol doses in preterm infants are lacking. Objectives: To determine the analgesic effects of different single intravenous paracetamol doses on pain from peripherally inserted central catheter (PICC) placement in preterm infants. Methods: In a blinded randomized controlled trial, the analgesic effects of 10-, 15-, and 20-mg/kg single-dose intravenous paracetamol before PICC placement were compared in neonates with a gestational age <32 weeks. Secondly, a separate age-matched nonrandomized control group receiving oral sucrose was included. Pain was assessed with the Premature Infant Pain Profile (PIPP) and the COMFORTneo score. Peak plasma concentrations of paracetamol were determined. Results: A total of 60 patients were included in the paracetamol dose groups (median gestational age = 27.8, IQR: 25.7-29.2 weeks). PIPP scores were comparable: median = 8 (IQR: 6-10.5), 7 (IQR: 6-9), and 8 (IQR: 6-10) for the 10-, 15-, and 20-mg/kg paracetamol groups, respectively (p = 0.94). COMFORTneo scores were not statistically different between the different paracetamol dose groups (p = 0.35). All randomized subjects, except for 3 who received 10 mg/kg of paracetamol, had peak paracetamol concentrations >9 mg/L. PIPP (p = 0.78) and COMFORTneo (p = 0.08) scores were also comparable between paracetamol- and sucrose-treated patients. Conclusions: We found no analgesic benefit from intravenous paracetamol studied in different single doses over sucrose for PICC placement in preterm infants. Paracetamol is not a suitable analgesic for this procedure in preterm infants.

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Effects of the Analgesic Acetaminophen (Paracetamol) and its para‐Aminophenol Metabolite on Viability of Mouse‐Cultured Cortical Neurons

Cited by 23 publications

References 18 publications

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Prenatal and perinatal analgesic exposure and autism: an ecological link

Randomized Controlled Trial Comparing Different Single Doses of Intravenous Paracetamol for Placement of Peripherally Inserted Central Catheters in Preterm Infants

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