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Black Necked Spitting Cobra

 

Figure 1

Naja nigricollis aka the Black Necked Spitting Cobra (BNSC) originates from Africa and lives in moist savannas near rivers and streams. The BNSC is are a venomous, front fanged snake that is responsible for many snakebite cases in southern Africa (as seen in figure 2).

As seen in figure 1, the species of snake can actually spray its venmon when threatened.

figure 2

 

Biotransformation: The bite or spray of venom from BNSC causes cytotoxic effects such as swelling and tissue necrosis but can also cause haemostatic disturbances such as abnormal blood clotting.

Toxicokinetics: Toxicity from a BNSC is caused from a

bite o

r a spray of the snake venom. When the venom is injected or absorbed into the skin, toxic effects can occur.

Carcinogenicity: There is currently little information available about the possibility of cancer causing effects associated with the venom of BNSCs.

Mechanism of Action (if known): The anticoagulant effects are caused by the inhibition of factor X

or thrombin, the lysis of fibrin, the activation of plasminogen, and/or the inhibition of platelet aggregation. When venom from a BNSC was injected into mice, it was seen to exhibit strong cytotoxic effects on the myogenic cell line CSC12.

Target organ(s): Target organs include heart, skin, liver, and lungs.

Signs and symptoms of toxicity: Bite from this species of snake can cause local swelling, bruising, blistering, bleeding, and even necrosis of the effected tissue (as seen in figure 3). Respiratory paralysis can occur if untreated.

Historical or unique exposures: The venom of the BNSC is widely used in research studies testing the effects of various antivenoms.

Treatments: Treatment for this type of snake bite is rapid admittance to a ER, sufficient wound care (flushing, cleaning, wrapping, etc.), support for impaired respiration. If paralytic feature of major local effects occurs, IV antivenom may be indicated.

Citations:

Vermaak, S. S., Visser, A., & le Roux, T. L. B. (n.d.). A deadly bed partner: M’Fesi (Mozambique spitting cobra). SA Orthopaedic Journal. Retrieved July 28, 2022, from http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S1681-150X2010000400011

Glatz, K. (2022, March 22). How far can spitting cobras shoot their venom? AZ Animals. Retrieved July 28, 2022, from https://a-z-animals.com/blog/how-far-can-spitting-cobras-shoot-their-venom/

Kazandjian, Taline D. et al. 2021. “Anticoagulant Activity of Naja Nigricollis Venom Is Mediated by Phospholipase A2 Toxins and Inhibited by Varespladib.” Toxins 13(5): 1–20.

Acrylonitrile

 

Acrylonitrile (ACN) is a colorless and volatile liquid with an odor that resembles onions or garlic. It is used in industries that produce rubber, resins, plastics, and synthetic fibers. It is also used to manufacture carbon fibers that are used in aircraft, defense, and aerospace industries.

 

 

 

 

 

 

Symptoms: When exposed to acrylonitrile, humans can experience irritation to the mucus membranes, headaches, nausea, dizziness, impaired judgment, difficulty breathing, limb weakness, cyanosis, convulsions and collapse.

 

Carcinogenicity: Acrylonitrile is also reasonably anticipated to be carcinogenic to humans as it may be related to an increased risk of lung or prostate cancer (1).

Toxicokinetics:Acrylonitrile can be absorbed into the body via inhalation of its vapors, by ingestion, or topically via the skin or eye.

Target organs include eyes, skin, cardiovascular system, liver, kidneys, and central nervous system.

Mechanism of Action: Acrylonitrile is readily absorbed into systemic circulation following exposure. It is metabolized in one of two ways: glutathione conjugation (produces 2-cyanoethylmercapturic acid)  and oxidation of cytochrome P450 (produces 2-cyanoethylene oxide which can then be conjugated to yield cyanide).

Genetic Toxocity: Acrylonitrile is not known to be genetrically toxic but there is some evidence of fetotoxicity in the offspring of rats exposed during pregnancy via inhalation or ingestion, but this was only seen in instances of significant maternal toxicity.

Treatment for cyanide poisoning caused by CAN toxicity is empiric because of how long it take for laboratory confirmation to be processed. Sodium thiosulfate and hydroxocobalmin have been used as antidotes for cyanide poisoning. Immediate first aid would include decontamination of the exposed area and possible intubation is the exposed person is not breathing.

History/Biomarkers: In May of 2013, a train that was transporting chemicals was derailed in Wetteren, Belgium and resulted in a leak of acrylonitrile. That May, 242 residents participated in a study to assess the human exposre of the solvent. N-2 cyanoethylvaline (CEV), a biomarker of ACN exposure, was measured in the participants blood. As there was a potential for CEV to show up In the blood of smokers, cotinine was also measured in the participants urine. In the evacuated spill zone, 37% on non-smokers and 40% of smokers have higher than reference values of CEV in their blood. Because the spill was not cleaned up for 108 days, the CAN seeped into the ground water and 5 wells also shows increased levels of ACN and continues to increase even after the contaminated soil was removed. It took about 170 days for the levels to decrease. In the photo below you can see the train crash and the acrylonitrile fumes moving up into the air (3).

  1. S. National Library of Medicine. (n.d.). Acrylonitrile. National Center for Biotechnology Information. PubChem Compound Database. Retrieved July 19, 2022, from https://pubchem.ncbi.nlm.nih.gov/compound/Acrylonitrile#section=Antidote-and-Emergency-Treatment
  2. Points, Key. 2007. “Acrylonitrile Toxicological Overview.” : 1–9.
  3. Paepe, P De et al. 2015. “The Wetteren Acrylonitrile Disaster: Management, Media Communication and Biomarker-Based Screening.”
  4. Take online courses. earn college credit. Research Schools, Degrees & Careers. Study.com | Take Online Courses. Earn College Credit. Research Schools, Degrees & Careers. (n.d.). Retrieved July 19, 2022, from https://study.com/academy/lesson/acrylonitrile-structure-manufacturing-process.html

Gold

Proton Number - Atomic Number - Density of Gold

Gold is a reddish-yellow element that can found in the Earth’s crust of 0.005ppm1 and small amounts can be found in sea water and on the ocean floor. Gold has been used for coinage, jewelry, and artifacts for over 4000 years and is considered a precious metal. Few people today are not in daily contact with gold or gold compounds as it found in most jewelry and has a wide range of industrial uses. Its bright color, density, high malleability, ductility, and capacity to conduct hear and electricity make it an invaluable element to our every day lives.

Gold is a transition metal that occurs naturally in its metallic state and exhibits a similar electron configuration to copper and silver and are known as “coinage” metals. Gold is insoluble in water and body fluids but its ionization constant is unknown. Gold nanoparticles are heavily used in scientific and technological studies because of their ease of synthesis and chemical stability and have been used in biomedical applications in chemical sensing, biological imaging, drug delivery, and cancer treatment. Because of this, knowledge of their potential toxicity and health impact is important before they can used in a clinical setting.

The most common form of biocompatibility studies on gold nanoparticle is the assessment for toxicity in vitro. These studies mainly focus of the viability of the cells in dose-dependent toxicity studies and evaluate cell survival and proliferation after exposure to the nanoparticles. Most studies have found the gold nanoparticles to be non-toxic invitro. In vivo studies in mice have also been done. Researchers found that the toxicity of the nanoparticles depended on the size of the particles. Interestingly, the smallest and largest sizes of the gold nanoparticles were seen to be nontoxic but the intermediate sizes were lethal to the animals. Many animals became severely sick with loss of appetite, weight loss, change in fur color, and reduced life span. This toxicity was linked to major organ damage in the liver, spleen, and lungs. The accumulation of the nanoparticles in the liver and spleen are caused by the  reticuloendothelial system2  

Please see below for more information on the toxicity of gold nanoparticles.

Low concentrations of gold are commonly found in the human body but do not seem to provide any nutritional benefit. The low concentrations could be caused by absorption via dermal contact, inhalation of dust, implantation of acupuncture needles, ear piercings, gold bearing prothesis, and even dental repair. Gold has no taste or smell and when absorbed into the body, the residues are eliminated in from the body in the hair, nails, bile, urine, and feces. Any gold that is retained in the body is rarely toxic. The skin and the eye are the target organs for gold deposition and discolorations can be formed.

Biomedical evidence shows gold ions that are absorbed into the tissues induce and bind metal-binding proteins (MBP). These MBPs include albumins, metallothioneins, y-globulin and histones1. The

ions bind to MBPS by the free thiol group of cystine residues. Gold is metabolized in the liver, kidney, spleen, lymph nodes, skin, salivary glands, bone and bone marrow.

Gold is not currently classifies as a carcinogen by the US Department of Health and Human Services but there is much evidence that gold miners are subject to much higher rates of lung cancer than many other professions. Actually, gold technology has been studied as an anticancer therapy as it can invoke cytotoxic and genotoxic changes in human hepatocellular carcinoma and mononuclear cells1. It has also be know to be the best single therapeutic substance in the treatment of rheumatoid arthritis.

Symptoms of gold toxicity include generalized pruritus, seborrheic dermatitis, urticaria, purpura, secondary anemia, exfoliative dermatitis, stomatitis, thrombopenic purpura, agranulocytosis, jaundice, gastroenteritis and conjunctivitis. Among additional toxic manifestations reported by others are peripheral neuritis, dizziness, nausea, vomiting, nephritis and acute yellow atrophy of the liver3. Toxicity can be treated by Dimercaprol or British Anti-Lewisite (BAL) (like lead and most other heavy metals). Please see below for a depiction of the symptoms and target organs of gold toxicity.

  1. Lansdown, Alan B.G. 2018. “GOLD: Human Exposure and Update on Toxic Risks.” Critical Reviews in Toxicology 48(7): 596–614. https://doi.org/10.1080/10408444.2018.1513991.
  2. Alkilany, A. M., & Murphy, C. J. (2010). Toxicity and cellular uptake of gold nanoparticles: what we have learned so far?. Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology, 12(7), 2313–2333. https://doi.org/10.1007/s11051-010-9911-8
  3. Prume, De, Gold Salts, and De Paris. 2022. “Therapy By.”
  4. YouTube. (2018, June 1). The toxicity of engineered gold nanoparticles made in South Africa. YouTube. Retrieved June 14, 2022, from https://www.youtube.com/watch?v=MdufDQJhZhw
  5. Gold toxicity. DoveMed. (n.d.). Retrieved June 14, 2022, from https://www.dovemed.com/diseases-conditions/gold-toxicity/
  6. Author. (2021, November 26). Gold – atomic number – atomic mass – density of gold. Nuclear Power. Retrieved June 14, 2022, from https://www.nuclear-power.com/gold-atomic-number-mass-density/
  7. CNBC. (2022, June 1). Gold rises from 2-week low as inflation worries persist. CNBC. Retrieved June 14, 2022, from https://www.cnbc.com/2022/06/01/gold-markets-us-treasury-yields-dollar.html

Pesticides – Blog Entry #1 – ROTENONE

ROTENONE

Rotenone is a Class II pesticide and is one of the oldest botanical insecticides that has been used as a piscicide, pesticide, and insecticide. It is derived from plants such as Derris elliptica from Asia, Lonchocarpus utilis from South America, and Piscidia piscipula from North America. Rotenone was first used by fishermen who would place pounded roots that contained rotenone into water in order to aid in the collection of fish. Today, the piscicide is diluted into bodes of water in order to eliminate invasive species of fish. Interestingly, rotenone is also used in marine research because it aids in the immobilization of fish for easier examination and estimation of population size. It is also used in home gardens for insect control and even flea and tick control on pets.

 

Veterinary Toxicology, Edited by Ramesh C. Gupta. ISBN: 978-0-12-370467-2

Rotenone is a very safe compound when used appropriately, but higher doses can be toxic to humans, animals, and fish. The absorption of rotenone into the gastrointestinal track is quite low without the aid of fats and oils and much more toxic when injected intravenously. It is metabolized in the liver by nicotinamide adenine dinucleotide phosphate (NADP)  line hepatic microsomal enzymes (1). Studies in rats and mice show that about 20% of a dose of rotenone is excreted in the urine within 24 hours of oral administration and unabsorbed rotenone is excreted in the feces (2).

In insects, rotenone acts by inhibiting the transfer of electrons from Fe-S in Complex I to ubiquonone in the electron transport chain, therefore preventing nicotinamide adenine dinucleotide (NADH) from converting into usable cellular energy. In animals, rotenone inhibits the oxidation of reduced NADH to  nicotinamide adenine dinucleotide (NAD). This blocks the oxidation of NAD substrates like glucamate, α-ketoglutarate, and pyruvate, as seen in figure 1. Rotenone also serves as an excellent inhibitor of the mitochondrial electron transport by inhibiting the respiratory chain between diphosphopyridine nucleotide and flavine (2). Because of this, chronic exposure to rotenone can alter mitochondrial fatty acid sequence and cause fatty changes in the liver that can cause cell death. Check out the above video for more information on rotenone’s mechanism of action or view figure one below.

Figure 1: Rotenone Mechanism of Action (5).

In mammals, acute toxicity is variable among species with an oral LD50 of 60-135mg/kg in rats and 350mg/kg in mice and female rodents are more susceptible that male rodents. Depression and convulsions are common clinical signs with acute toxicity of rotenone and oral ingestion caused pharyngitis, nausea, vomiting, gastric pain, clonic convulsions, muscle tremors, lethargy, and incontinence (2). In some animal studies, hypoglycemia and liver failure have been found.

An interesting use of rotenone is its ability to create Parkinson’s disease (PD) models in research. As rotenone is an inhibitor of complex I in experimental animals. Rotenone is lipophilic and can cross the blood brain barrier (BBB) to access the brain. Chronic exposure to rotenone in the brain will eventually being to degrade the dopamine neurons in the substantia nigra (similar to PD). For more information of the rotenone pathway in PD models, please refer to figure 2 below.

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Figure 2: Rotenone pathway in substantia nigra of brain (6).

In study done on E344/N rats, toxicity and carcinogenicity of rotenone was studied. 50 rats of each sex were given rotenone in the diet for 103 weeks. Reduction in weight gain was observed but no neoplastic effects in either sex occurred. Parathyroid adenomas were seen in a few male rats but this incidence was rare (4).

Currently, there is no known antidote for rotenone. Therefore, treatment relies on supportive and symptomatic care. Washing any contaminated skin, avoiding vomiting if convulsions are present, performing gastric lavage if a large amount of rotenone is ingested, administering seizure medications such as diazepam if necessary, and glucose IV if hypoglycemia is present (1).

 

1.) Gupta, Ramesh C. 2007. “Rotenone.” : 499–501.

2.) Hayes, W. (1982). Rotenone and related materials. Pesticides Studied in Man, , 81-86. Retrieved from www.scopus.com

3.) Greenamyre, J. Timothy, Ranjita Betarbet, and Todd B. Sherer. 2003. “The Rotenone Model of Parkinson’s Disease: Genes, Environment and Mitochondria.” Parkinsonism and Related Disorders 9(SUPPL. 2): 59–64.

4.) Abdo, K. M., Eustis, S. L., Haseman, J., Huff, J. E., Peters, A., & Persing, R. (1988). Toxicity and carcinogenicity of rotenone given in the feed to F344/N rats and B6C3F1 mice for up to two years. Drug and chemical toxicology, 11(3), 225–235. https://doi.org/10.3109/01480548809017879

5.) Bordt, Evan A. et al. 2017. “The Putative Drp1 Inhibitor Mdivi-1 Is a Reversible Mitochondrial Complex I Inhibitor That Modulates Reactive Oxygen Species.” Developmental Cell 40(6): 583-594.e6.

6.) Abdelsalam, Rania M., and Marwa M. Safar. 2015. “Neuroprotective Effects of Vildagliptin in Rat Rotenone Parkinson’s Disease Model: Role of RAGE-NFκB and Nrf2-Antioxidant Signaling Pathways.” Journal of Neurochemistry 133(5): 700–707.

7.)TXLutheran. (2017, March 8). Inhibition of complex I of the electron transport chain by Rotenone. YouTube. Retrieved May 31, 2022, from https://www.youtube.com/watch?v=EOdxz_9Qfl4