Posts

Mushrooms

Mushrooms

Mushrooms, derived from the Old French word mousseron, are a popular type of fungus.

There are edible (non-toxic) and non-edible (toxic) types.

Historical/Unique exposures

Psilocybin mushrooms produce psychedelic effects.

  • Believed to have been used in early European religious rituals.
  • 1955: Valentina Pavlovna Wasson and R. Gordon Wasson were the first European Americans to participate in mushroom ceremonies.
  • 200 other types of mushrooms can produce psychedelic effecs.

Edible uses:

  • Originally discovered in 1650 by a French melon grower.
  • A fascinating article/timeline of mushroom cultivation/use found here.

Source

Mushrooms help with breaking down materials such as plants, animals, and other food sources.

Typically found around:

  • Decaying trees/plants
  • Animal carcasses
  • Soil
  • ¬†Manure

Biotransformation

Mushrooms, specifically the oyster mushroom (image 2) are actually used as biotransformers.

An article describing the process of oyster mushrooms biotransforming orange waste can be found here.

Toxicokinetics

As stated, there are two types of mushrooms. Toxic and non-toxic.

A link to the toxicological profiles of all types of mushrooms are found here.

Toxicity:

  • the most common cause of toxicity is lack of recognition of toxic mushrooms

Pharmicokinetics/Mechanism of Action:

  • Each mushroom has at least one toxin
  • The mechanism of action is different for each toxin
  • Due to different mechanisms of action, target organs also differ.
  • The mechanism of toxicity (action) for each toxin is also highlighted in the article provided above.

 

Signs and Symptoms of Toxicity

  • Sweating
  • Tearing
  • Drooling
  • Vomiting
  • Diarrhea
  • Shortness of breath

Treatments

Toxicity is treated with atropine.

Systematic treatment is also recommended.

*Physostigmine antidote is specific for muscimol toxicity from Amanita muscaria and Tricholoma muscarium.

Biomarkers

Liver function is heavily targeted by hepatotoxic mushrooms.

Biomarkers for these mushrooms include:

  • aspartate aminotransferase (AST)
  • alanine aminotransferase (ALT)
  • alkaline phosphatase
  • lactic dehydrogenase (LDH

Biomarkers present 36-72 hours after ingestion.

Carcinogenicity

Some mushrooms contain carcinogenic toxins.

These toxins are killed with high temperatures reached when cooking.

 

 

Ethanol

Link

Ethanol is a very commonly used chemical; whether it is at home drinking a nice cold one, or filling up the tank at the gas station. Ethanol is a big part of our everyday lives.

Link

Sources:

Ethanol is also known as ethyl-alcohol because of its chemical composition.

Typically found in:

  • Fuel when mixed with gasoline
  • Alcoholic beverages
  • Chemistry labs to wash equipment (purest form)

Ethanol is formed by fermenting different types of starch such as:

  • corn
  • wheat
  • grain
  • barley
  • potatoes

Biotransformation:

Ethanols is developed from different things and can be turned to different things via biotransformation.

  • External fermentation of ethanol via starches for the purpose of use or consumption.
  • Internal fermentation of ethanol in the body via starches.
  • Oxidation of ethanol to form acetaldehyde by NAD+
    • Formation of acetic acid from acetaldehyde

Toxicokinetics:

***the rate of toxicokinetics can vary due to age, gender, weight, etc.

Absporbtion

  • GI tract (small intestine) when ingested
  • Lungs when inhaled
  • Sometimes absorbed by the skin.

Distribution

  • Ethanol is distributed equally throughout the body depending on:
    • the amount of water in that area.
    • blood flow to that area
    • tissue mass

Metabolism:

  • Via the liver

Elimination:

  • Typically via breath, urine, sweat, saliva, feces, and breast milk.

Mechanism of action:

Link

-The mechanism of action of alcohol is increased production of GABA. GABA is an inhibitory neuron and CNS activity is reduced due to the inhibitory effects of GABA.

-Ethanol can also act on the reward pathways by releasing excess amounts of dopamine.

Link

Target organs:

Ethanol primarily targets the brain/central nervous system (CNS).

Signs & Symptoms:

  • confusion
  • vomiting
  • convulsions
  • respiratory depression
  • hypothermia
  • unconsciousness/ coma

*Alcohol poisoning can result in DEATH.

Treatments:

In less severe cases, patients will be monitored until it passes through their system.

In severe cases:

  • Stomach pumping/fluid flushing
  • IV fluids to help with dehydration
  • Insertion of breathing tube
  • Insertion of catheter

Carcinogenicity:

Research strongly shows a relationship between ethanol/alcohol consumption/exposure and cancer. It is classified as a class 1 carcinogen which is very carcinogenic to humans.

Primary types of cancer related to ethanol exposure are:

  • Head and neck
  • Esophageal
  • Liver
  • Breast
  • Colorectal
Link

Genetic Susceptibility/ Heritable Traits:

Ethanol in alcohol

Abuse of Alcohol

Alcoholism

Alcoholism is heavily related to mental health disorders such as:

  • depression
  • anxiety
  • schizophrenia
  • etc.
Link

Historical/Unique Exposures:

In 1920, the United states banned all use, trade, production, etc. of alcoholic beverages. This ban was a constitutional ban referred to in the 18th amendment. In 1933, the ban on alcohol was lifted and prohibition was ended.

Biomarkers:

Production from phase II liver metabolism:

  • ethyl glucuronide
  • ethyl sulfate

Other:

  • Phosphoatidyethanol
  • fatty acid ethyl esters

Essentiality and Deficiency:

Vitamin deficiencies may increase the risk of liver damage caused by ethanol.

Lead

 

Sources:

Some sources of lead include:

-Old paints

-Batteries

-Leaded Fuel

-Old toys made in China

-Glaze finish on ceramics

-Fishing weights/sinkers

-Bullets

Toxicokinetics:

Typically ingested orally into the GI tract by children due to eating or chewing on items containing lead. Absorption amounts depend on how full the stomach is (i.e. empty vs. full).

It also depends on any mineral deficiencies of: zinc, calcium, or iron.

Distribution of lead typically to soft tissue in the liver and kidneys.

Lead in the blood is found in erythrocytes bound to hemoglobin. About half of the lead found in the blood is due to lead being released from the bone.

Excretion primarily through the kidneys into urine.

*Lead is able to cross through the placenta to the fetal tissue.

 

Carcinogenicity:

Recently inorganic lead has been classified as potentially linked to cancer in humans.

Organic lead compounds do not seem to be carcinogenic.

Mechanism of action:

Lead primarily causes anemia by inhibiting ALAD and ferrochelatase. ALAD is a catalyst condensing ALA into Phorophobilinogen (PBG). Ferrochelatase is a catalyst inserting iron into protopophyrin rings to produce heme.

Target Organs:

The Central Nervous System (CNS) and blood

Signs and Symptoms of Toxicity:

*Symptoms vary by age group

Newborns:

-Premature birth, Slowed growth, Low weight at birth

Children:

-Seizures, Vomiting, Constipation, Hearing Loss, Delays in Development, Learning Disabilities, Appetite loss, Weight loss, Abdominal pain, Loss of hearing, Abdominal Pain, Pica.

Adults:

-High BP, Joint and muscle pain, abdominal pain, mood disorders, constipation, confusion, headache. Women-miscarriage, still born, premature delivery of baby. Men- Abnormal sperm or sperm count.

Treatments:

Basic treatment is removal of lead source. Reducing exposure can reduce levels of lead in the blood.

Severe cases treatment is chelation therapy (children) and EDTA chelation therapy (adults).

Genetic Susceptibility or Heritable Traits:

Small differences in DNA sequencing of ALAD and VDR genes could impact how lead is handled in the body. ALAD has two alleles (ALAD1 and ALAD2) that have already been observed to have an impact on the pharmacokinetics of lead. However, recently there have been observations of two VDR alleles (VDRb and VDRB) impacting pharmacokinetics of lead.

Biomarkers of lead:

Primarily found in urine levels and blood levels. Below are the different blood and urine biomarkers.

Historical or Unique Exposures:

Lead exposure is unavoidable considering lead is found in earths very own atmosphere. However, the most notable exposures have been from lead house paint. Children used to suffer from lead poisoning and exposure in houses with old lead paint chips or dust containing lead paint. This exposure resulted because of hand-to-mouth contact.

Essentiality and Deficiency:

As stated above, lead poisoning can be increased significantly by different mineral deficiencies. However, lead deficiency has very minimal affects.

Nicotine

Image Here

Uses

Nicotine, commonly found in tobacco, is one of the most popular and accepted drugs today. Throughout history, people have found new and unique ways to administer nicotine into their body. Inhalation is the most popular route of administration.

Image Here

Whether it is from a pipe with pure tobacco, cigarettes, or (the newest trend) a vape, nicotine is mostly consumed through smoking/inhalation. Though nicotine is considered one of the most popular drugs, it is rarely talked about as a pesticide. Did you know nicotine can be used as a pesticide/insecticide?

Biotransformation

Nicotine is turned into hydroxylated-pyridine intermediates by bacteria. Hydroxylated-pyridine intermediates are the precursors necessary to develop insecticides.

Pictured below are different intermediates formed by degradation of nicotine.

Image Here

Toxicokinetics

The toxicokinetics of nicotine are complex and can be found in an academic journal here

Mechanism of Action

Nicotine exposure/use releases dopamine by activating acetylcholine receptors that function like a4b2 subunit of nicotinic acetylcholine receptors (nAChRs) in the nucleus accumbens. Simply put, when used as a pesticide nicotine blocks synaptic transmission in the central nervous system by overstimulation of neurons.

Target Organ(s)

Nicotinic acetylcholine receptors in the (nAChRs)

Primarily the heteromeric a4b2 subunit (pictured under leter D below)

*The triangle represents the acetylcholine receptor(s) on the subunit.Image Here

Signs & Symptoms of Toxicity

The most common symptom is vomiting (more than 50% of toxicity cases).

Short term exposure (less than 8 hours) can cause mild and severe symptoms:

Mild:

tremor, increased heart rate, respiration, bp, and alertness.

Severe:

involuntary muscle movements or seizure, abnormal heart rate/rhythm bradycardia, hypotension and paralysis of muscles in charge of breathing.

*Death may occur*

Genetic susceptibility or heritable traits

As stated above, nicotine is used as a drug among humans and genetic susceptibility to nicotine use primarily effects dependence to the substance.

Pictured below is a graph showing different candidate genes that could contribute to genetic susceptibility to nicotine dependence.

Image Here

Treatments

Atropine, a common antidote for cholinergic toxicity/nicotine toxicity, is administered intravenously.

Image Here

Biomarker

 Cotintine is a biomarker for nicotine usage or exposure.

Found in urine, blood, hair, nails, and saliva.