Simba care Hand Sanitizer & Body Spray

Dosage

Children: Refer to specific product guidelines or BNF for Children for accurate dosing information based on the formulation and indication.

Adults: Refer to specific product guidelines or BNF for accurate dosing information based on the formulation and indication.

Mechanism of action

The mechanism of action of compounds varies depending on their specific components. Generally, compounds can work through synergistic effects where the combined action of the ingredients leads to enhanced therapeutic outcomes. This may involve interactions at specific receptor sites, modulation of enzyme activity, or alteration of physiological pathways.

Pharmacodynamics

Pharmacodynamics of compounds is dependent on the individual pharmacological properties of each active ingredient within the formulation. This can include effects on receptor binding, ion channel modulation, and influence on neurotransmitter levels, leading to a range of therapeutic effects such as analgesia, anti-inflammatory action, or antimicrobial activity.

Pharmacokinetics

Pharmacokinetics of a compound involves the absorption, distribution, metabolism, and excretion of the active ingredients. Depending on their chemical nature, some compounds may exhibit rapid absorption, while others may have prolonged release characteristics. The bioavailability and half-life of each component can differ significantly, affecting overall efficacy and safety profiles.

Pregnancy

Use only if clearly needed, as safety in pregnancy is not established.

Breast-feeding

Caution is advised, as it is not known if the drug is excreted in human milk.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Indications

• Alcohol use disorder
• Acute alcohol intoxication
• Antiseptic for skin disinfection

Mechanism of action

Ethanol affects the brain’s neurons in several ways. It alters their membranes, ion channels, enzymes, and receptors. Ethanol binds directly to the receptors for acetylcholine, serotonin, GABA, and NMDA receptors for glutamate. The sedative effects are mediated through binding to GABA receptors and glycine receptors, while also inhibiting NMDA receptor functioning. As an anti-infective, ethanol acts as an osmolyte, disrupting the osmotic balance across cell membranes. The acute effects result from competitive inhibition of glycine binding to NMDA receptors, leading to disrupted glutamatergic neurotransmission.

Pharmacodynamics

Ethanol produces cellular injury through dehydration and precipitation of cytoplasm, contributing to its bactericidal and antifungal actions. It can lead to neuritis and nerve degeneration when injected near nerve tissues. Up to 98% of ethanol in the body is oxidized, primarily by the hepatic enzyme alcohol dehydrogenase. Its modulation of neurotransmitter receptors, particularly GABA and NMDA, leads to its sedative properties and potential for developing tolerance with chronic use.

Pharmacokinetics

Ethanol is readily absorbed from the gastrointestinal tract and distributed throughout the body. It has a volume of distribution of approximately 0.5 to 0.6 L/kg. Ethanol is metabolized predominantly in the liver by alcohol dehydrogenase to acetaldehyde, which is further oxidized to acetic acid by aldehyde dehydrogenase. The elimination half-life of ethanol varies but is generally around 4 to 5 hours. Factors such as age, sex, body weight, and genetic variability can influence ethanol metabolism.

Contra-indications

• Hypersensitivity to ethanol
• Acute alcohol intoxication
• Severe liver disease
• Pregnancy (in non-medicinal use)
• Severe pancreatitis
• Severe head injury or intracranial bleeding

Adverse effects

• Dizziness
• Nausea
• Vomiting
• Headache
• Sedation
• Cognitive impairment
• Respiratory depression
• Hypotension
• Gastrointestinal bleeding
• Alcohol withdrawal syndrome

Interactions

• CNS depressants (e.g., benzodiazepines, opioids) may enhance sedative effects
• Disulfiram may cause unpleasant reactions when taken with ethanol
• Acetaminophen may increase hepatic toxicity when used with ethanol
• Warfarin may have altered effects when used with ethanol

Precautions

• Caution in patients with a history of alcohol abuse
• Use with caution in patients with hepatic impairment
• Monitor for signs of respiratory depression
• Consider potential for addiction and withdrawal symptoms
• Use in moderation in older adults due to increased sensitivity

Pregnancy

Ethanol should be avoided during pregnancy due to the risk of fetal alcohol spectrum disorders.

Breast-feeding

Ethanol can pass into breast milk; breastfeeding should be avoided for a minimum of 2 hours after consumption.

Storage

Store in a cool, dry place away from light. Keep tightly closed and out of reach of children.

Formulations

• Oral solutions
• Topical antiseptics
• Intravenous formulations
• Medicinal tinctures

Dosage

Children: As with adults, dosing for children is highly variable and specific to the product used. It is advisable to refer to product guidelines and consult a healthcare professional.

Adults: Dosing varies widely based on the specific product and its intended use, with no standardized dosage for fragrance as it is generally applied topically or used in the environment.

Mechanism of action

Fragrances primarily act by stimulating the olfactory receptors in the nasal cavity, which send signals to the brain's olfactory bulb. This process is responsible for the perception of smell and can evoke emotional responses, enhance mood, and even influence behavior. The specific compounds in fragrances can interact with various biochemical pathways, but their exact mechanisms can vary widely depending on the individual components and their concentrations.

Pharmacodynamics

The pharmacodynamics of fragrance compounds can involve modulation of neurotransmitter activity in the brain, particularly those associated with mood and emotional responses. Certain fragrance compounds may have calming effects, potentially influencing the levels of stress hormones and promoting relaxation. However, responses can be highly subjective and vary from person to person.

Pharmacokinetics

The pharmacokinetics of fragrance components depend on their chemical nature. Many volatile aromatic compounds can be rapidly absorbed through the skin or inhaled, leading to quick onset of effects. Metabolism may occur in the liver, and elimination can happen through urine or exhalation. The half-lives of these compounds can vary significantly based on their structure and the route of exposure.

Adverse effects

• Allergic reactions
• Skin irritation
• Respiratory issues
• Headaches
• Nausea

Precautions

• Use with caution in individuals with known allergies
• Avoid use in those with respiratory conditions like asthma
• Patch testing recommended prior to widespread use on skin

Pregnancy

Fragrance use during pregnancy should be limited, as some ingredients may pose risks to fetal development.

Breast-feeding

Generally considered safe, but caution is advised due to potential for skin absorption and transfer to infant.

Storage

Store in a cool, dry place away from direct sunlight, tightly sealed to prevent evaporation.

Formulations

• Perfumes
• Colognes
• Body sprays
• Scented lotions
• Candles
• Essential oils

Indications

• Constipation
• Decreased intraocular pressure

Dosage

Children: For children, refer to the BNF for Children for appropriate glycerin dosing guidelines.

Adults: For constipation, glycerin can be administered rectally as a suppository. Follow specific product guidelines for dosage.

Mechanism of action

When administered rectally, glycerine exerts a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexively stimulating evacuation. Additionally, glycerine decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, leading to fluid movement out of the aqueous and vitreous humors into the bloodstream.

Pharmacodynamics

Glycerine is commonly classified as an osmotic laxative but may also exert local irritant effects, lubricating, and fecal softening actions. Its onset of action typically occurs within 15 to 30 minutes when used as a suppository.

Pharmacokinetics

Glycerine is readily absorbed and metabolized in the body. It undergoes glycerol metabolism pathways, contributing to various biochemical processes including phospholipid biosynthesis. The pharmacokinetic profile of glycerine indicates a rapid onset of action due to its osmotic properties.

Adverse effects

• Abdominal cramps
• Diarrhea
• Nausea
• Vomiting
• Electrolyte imbalance

Precautions

• Use with caution in patients with renal impairment
• May cause dehydration if used excessively
• Monitor for electrolyte disturbances in prolonged use

Pregnancy

Glycerin is generally considered safe to use during pregnancy for indicated conditions. Always consult a healthcare provider before use.

Breast-feeding

Glycerin is unlikely to be harmful in breastfeeding mothers. Consult a healthcare provider for specific guidance.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Formulations

• Suppositories
• Oral solution

Indications

• Oxidative stress-related conditions
• Inflammatory conditions
• Potential anti-aging applications
• Vascular health enhancement

Dosage

Children: Refer to specific product formulations and guidelines, as dosing can vary based on the concentration of hydrogen in the product used.

Adults: Refer to specific product formulations and guidelines, as dosing can vary based on the concentration of hydrogen in the product used.

Mechanism of action

Molecular hydrogen acts primarily as an antioxidant and anti-inflammatory agent. It is believed to exert its beneficial effects through the activation of the Nrf2 pathway, which enhances the expression of antioxidant enzymes and protects cells from oxidative stress. Hydrogen-rich environments have been shown to mitigate the harmful effects of various toxins on human umbilical vein endothelial cells, thereby promoting vascular health and longevity.

Pharmacodynamics

Hydrogen's pharmacodynamic properties are linked to its role as a potent antioxidant, which reduces reactive oxygen species (ROS) and modulates inflammation. It has been documented to counteract cellular senescence in endothelial cells, thereby maintaining vascular integrity and promoting overall health. The long-lasting effects of hydrogen exposure can be observed even after its concentration in the medium has decreased, suggesting a sustained activation of protective cellular pathways.

Pharmacokinetics

Hydrogen is a gaseous molecule that diffuses rapidly across biological membranes. Its absorption and distribution in the body are influenced by the method of administration, with hydrogen-rich water being a common delivery form. Once in the bloodstream, hydrogen is quickly utilized by tissues, and its concentration diminishes rapidly, with a half-life that can vary based on conditions. The elimination of hydrogen primarily occurs via exhalation, making it a non-toxic molecule with a favorable safety profile.

Pregnancy

Hydrogen is generally considered safe during pregnancy, but it is advisable to consult a healthcare provider for specific recommendations.

Breast-feeding

Hydrogen is considered safe during breastfeeding, but as with any substance, it is recommended to discuss with a healthcare provider.

Storage

Hydrogen should be stored in a cool, dry place away from direct sunlight and heat sources, in appropriate gas cylinders designed for compressed gases.

Formulations

• Hydrogen gas (H2)
• Hydrogen-rich water

Mechanism of action

Hydrogenphosphate acts as a substrate for various enzymatic reactions where phosphate groups are transferred or incorporated into organic molecules. It is involved in metabolic pathways such as nicotine biosynthesis and NAD/NADH cycling, facilitating biochemical reactions that are vital for cellular function.

Pharmacodynamics

Hydrogenphosphate is crucial for maintaining cellular homeostasis. It regulates acid-base balance and is involved in energy metabolism. The phosphate groups it provides are integral to the structure and function of ATP, which is the primary energy currency of the cell. Additionally, hydrogenphosphate influences signal transduction pathways through phosphorylation and dephosphorylation processes.

Pharmacokinetics

Hydrogenphosphate is readily absorbed in the gastrointestinal tract and distributed throughout the body. Its elimination primarily occurs through renal excretion, where it is filtered and reabsorbed by the kidneys. The balance of hydrogenphosphate levels is tightly regulated by various physiological mechanisms to ensure proper metabolic function.

Pregnancy

There is limited information regarding the safety of hydrogenphosphate in pregnancy. Consult relevant guidelines and consider potential risks versus benefits.

Breast-feeding

Data on the excretion of hydrogenphosphate in human milk are not available. Caution is advised.

Storage

Store in a cool, dry place away from direct sunlight. Ensure containers are tightly closed.

Indications

• Topical antiseptic for minor cuts and abrasions
• Wound cleansing
• Deodorizing agent

Dosage

Children: For paediatric use, hydrogen peroxide can be applied topically as a 3% solution. Consult the BNF for Children for detailed dosing guidance.

Adults: Hydrogen peroxide is typically applied topically as a 3% solution. It can be used to cleanse the affected area one to three times daily. For specific dosing, refer to the BNF.

Mechanism of action

The production of free hydroxyl radicals in the Fenton reaction is thought to be the basis of the biocidal actions of hydrogen peroxide. Free radicals lead to oxidative damage to proteins and membrane lipids in vivo. The release of nascent oxygen upon contact with catalase-containing tissues exerts antibacterial action, while effervescence mechanically loosens tissue debris and pus. Hydrogen peroxide is particularly effective on wounds, denuded areas, and mucous membranes.

Pharmacodynamics

Hydrogen peroxide exhibits antimicrobial properties against a wide range of microorganisms, including resistant forms such as bacterial spores and protozoal cysts. It acts as an oxidative biocide, generating free radicals that induce damage to DNA, proteins, and membrane lipids via oxidation. Its mechanical action of effervescence assists in the removal of tissue debris, which is a crucial aspect of its effectiveness in wound management.

Pharmacokinetics

Hydrogen peroxide's pharmacokinetics are not extensively detailed in the literature, but it is known to have poor tissue and wound penetration. The presence of reactive organic materials, such as pus and blood, diminishes its efficacy. The mechanical action of effervescence is significant in enhancing its antibacterial effects, particularly in contaminated wounds.

Adverse effects

• Skin irritation
• Burning sensation
• Allergic reactions

Precautions

• Avoid contact with eyes and mucous membranes
• Use with caution in patients with a history of hypersensitivity
• Do not apply to deep or puncture wounds

Pregnancy

Hydrogen peroxide should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult a healthcare provider before use.

Breast-feeding

Caution is advised when using hydrogen peroxide while breastfeeding. Consult a healthcare provider for guidance.

Storage

Store in a cool, dry place away from light and out of reach of children. Keep in tightly closed containers.

Formulations

• Topical solution
• Ointment

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Mechanism of action

Ethanol affects the brain’s neurons in several ways. It alters their membranes as well as their ion channels, enzymes, and receptors. Alcohol also binds directly to the receptors for acetylcholine, serotonin, GABA, and the NMDA receptors for glutamate. The sedative effects of ethanol are mediated through binding to GABA receptors and glycine receptors (alpha 1 and alpha 2 subunits). It also inhibits NMDA receptor functioning. In its role as an anti-infective, ethanol acts as an osmolyte or dehydrating agent that disrupts the osmotic balance across cell membranes. ... Ethanol is known to affect a large number of membrane proteins that participate in signaling pathways such as neurotransmitter receptors, enzymes, and ion channels, and there is extensive evidence that ethanol interacts with a variety of neurotransmitters. The major actions of ethanol involve enhancing the inhibitory effects of gamma-aminobutyric acid (GABA) at GABAa receptors and blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate, an excitatory amine acid (EAA) receptor. Animal studies indicate that the acute effects of ethanol result from competitive inhibition of glycine binding to NMDA receptor and disruption of glutamatergic neurotransmission by inhibiting the response of the NMDA receptor. Persistent glycine antagonism and attenuation of glutamatergic neurotransmission by chronic ethanol exposure results in tolerance to ethanol by enhancing EAA neurotransmission and NMDA receptor upregulation. The latter appears to involve selective increases in NMDA R2B subunit concentrations and other molecular changes in specific brain loci. The abrupt withdrawal of ethanol thus produces a hyperexcitable state that leads to the ethanol withdrawal syndrome and excitotoxic neuronal death. GABA-mediated inhibition, which normally acts to limit excitation, is eliminated during ethanol withdrawal syndrome and further intensifies this excitation. In addition, NMDA receptors function to inhibit the release of dopamine in the nucleus accumbens and mesolimbic structures, which modulate the reinforcing action of addictive xenobiotics such as ethanol. By inhibiting NMDA receptor activity, ethanol could increase dopamine release from the nucleus accumbens and ventral tegmental area and could thus create dependence. Chronic ethanol administration also results in tolerance, dependence, and an ethanol withdrawal syndrome, mediated, in part, by desensitization and or downregulation of GABAa receptors. The development of alcoholic ketoacidosis (AKA) requires that a combination of physical and physiologic events occur. The normal response to starvation and depletion of hepatic glycogen stores is for amino acids to be converted to pyruvate. Pyruvate can serve as a substrate for gluconeogenesis, be converted to acetyl-CoA, which can enter the Krebs cycle or can be utilized in various biosynthetic pathways (eg, fatty acid, ketone bodies, cholesterol, and acetylcholine) ... Ethanol metabolism generates NADH, resulting in an excess of reducing potential. This high redox state favors the conversion of pyruvate to lactate, diverting pyruvate from being a substrate for gluconeogenesis. To compensate for the lack of normal metabolic substrates, the body mobilizes fat from adipose tissue and increased fatty acid metabolism as an alternative source of energy. This response is mediated by a decrease in insulin and an increased secretion of glucagon, catecholamines, growth hormone, and cortisol. Fatty acid metabolism results in the formation of acetyl-CoA and it combines with the excess acetate that is generated from ethanol metabolism to form acetoacetate. Most of the acetoacetate is reduced to beta-hydroxybutyrate due to the excess reducing potential or high redox state of the cell. Volume depletion interferes with the renal elimination of acetoacetate and beta-hydroxybutyrate, and contributes to the acidosis. An elevated lactate concentration may result from shunting from pyruvate or

Pharmacodynamics

Alcohol produces injury to cells by dehydration and precipitation of the cytoplasm or protoplasm. This accounts for its bacteriocidal and antifungal action. When alcohol is injected in close proximity to nerve tissues, it produces neuritis and nerve degeneration (neurolysis). Ninety to 98% of ethanol that enters the body is completely oxidized. Ethanol is also used as a cosolvent to dissolve many insoluble drugs and to serve as a mild sedative in some medicinal formulations. Ethanol also binds to GABA, glycine, NMDA receptors and modulates their effects. Ethanol is also metabolised by the hepatic enzyme alcohol dehydrogenase.

Mechanism of action

When administered rectally, glycerin exerts a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexively stimulating evacuation. Glycerin decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream. Glycerin (glycerol) and sorbitol are hyperosmotic laxatives. When administered rectally, glycerin and sorbitol exert a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexly stimulating evacuation. The extent to which the simple physical distention of the rectum and the hygroscopic and/or local irritant actions are responsible for the laxative effects of some of these drugs is not known. Only extremely high oral doses of sorbitol (25 g daily) or glycerin exert laxative action. /Glycerin/ decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream. The physicochemical effects of a series of alkanols, alkanediols and glycerol on erythrocyte shape and hemolysis at 4 and 20 degrees C were examined. We calculated the dielectric constant of the incubation medium, Ds, and the dielectric constant of the erythrocyte membrane Dm in the presence of organic solutes. The ratio Ds/Dm = -38.48 at 20 degrees C defines the normal biconcave shape in a medium without hemolytic agents. A decrease in Ds/Dm favors externalization or internalization with consequent hemolysis. Alkanols and alkanediols convert biconcave erythrocytes into echinocytes, which is accompanied by an increase in the projected surface area. Glycerol converts biconcave erythrocytes into stomatocytes, which was accompanied by a marginal decrease in the projected surface area. Progressive externalization in alkanols and alkanediols or internalization in glycerol resulted in a decrease in the projected surface area and the formation of smooth spheres. The degree of shape change induced was related to the degree of hemolysis and the ratio Ds/Dm. A decrease in temperature reduced both the degree of shape change and hemolysis. .../Thus/ physicochemical toxicity may be a result of a temperature dependent hydrophobic interaction between the organic solutes and the membrane and is best interpreted by the ability of the solutes to change Ds and Dm.

Pharmacodynamics

Glycerin is commonly classified as an osmotic laxative but may act additionally or alternatively through its local irritant effects; it may also have lubricating and fecal softening actions. Glycerin suppositories usually work within 15 to 30 minutes.

Mechanism of action

Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2 on endothelial senescence and clarified the mechanisms involved. Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium. The baseline H2concentration in hydrogen-rich medium was 0.55 +/- 0.07 mmol/L. This concentration gradually decreased, and H2 was almost undetectable in medium after 12 hr. At 24 hr after TCDD exposure, HUVECs treated with TCDD exhibited increased 8OHdG and acetyl-p53 expression, decreased nicotinamide adenine dinucleotide (NAD(+))/NADH ratio, impaired Sirt1 activity, and enhanced senescence-associated beta-galactosidase. However, HUVECs incubated in hydrogen-rich medium did not exhibit these TCDD-induced changes accompanying Nrf2 activation, which was observed even after H2 was undetectable in the medium. Chrysin, an inhibitor of Nrf2, abolished the protective effects of H2 on HUVECs. H2 has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. /Hydrogen-rich water/ Amyloid beta (Abeta) peptides are identified /as a/ cause of neurodegenerative diseases such as Alzheimer's disease (AD). Previous evidence suggests Abeta-induced neurotoxicity is linked to the stimulation of reactive oxygen species (ROS) production. The accumulation of Abeta-induced ROS leads to increased mitochondrial dysfunction and triggers apoptotic cell death. This suggests antioxidant therapies may be beneficial for preventing ROS-related diseases such as AD. Recently, hydrogen-rich water (HRW) has been proven effective in treating oxidative stress-induced disorders because of its ROS-scavenging abilities. However, the precise molecular mechanisms whereby HRW prevents neuronal death are still unclear. In the present study, we evaluated the putative pathways by which HRW protects against Abeta-induced cytotoxicity /in SK-N-MC cells/. Our results indicated that HRW directly counteracts oxidative damage by neutralizing excessive ROS, leading to the alleviation of Abeta-induced cell death. In addition, HRW also stimulated AMP-activated protein kinase (AMPK) in a sirtuin 1 (Sirt1)-dependent pathway, which upregulates forkhead box protein O3a (FoxO3a) downstream antioxidant response and diminishes Abeta-induced mitochondrial potential loss and oxidative stress. Taken together, our findings suggest that HRW may have potential therapeutic value to inhibit Abeta-induced neurotoxicity. /Hydrogen-rich water/ The NLRP3 inflammasome, an intracellular multi-protein complex controlling the maturation of cytokine interleukin-1beta, plays an important role in lipopolysaccharide (LPS)-induced inflammatory cascades. Recently, the production of mitochondrial reactive oxygen species (mtROS) in macrophages stimulated with LPS has been suggested to act as a trigger during the process of NLRP3 inflammasome activation that can be blocked by some mitochondria-targeted antioxidants. Known as a ROS scavenger, molecular hydrogen (H2) has been shown to possess therapeutic benefit on LPS-induced inflammatory damage in many animal experiments. Due to the unique molecular structure, H2 can easily target the mitochondria, suggesting that H2 is a potential antagonist of mtROS-dependent NLRP3 inflammasome activation. Here we have showed that, in mouse macrophages, H2 exhibited substantial inhibitory activity against LPS-initiated NLRP3 inflammasome activation by scavenging mtROS. Moreover, the elimination of mtROS by H2 resultantly inhibited mtROS-mediated NLRP3 deubi

Mechanism of action

The production of free hydroxyl radicals in the Fenton reaction is thought to be the basis of biocidal actions of hydrogen peroxide. Free radicals eventually lead to oxidative damage proteins and membrane lipids _in vivo_. The oxidizing radical as the ferryl radical induces DNA oxidation. Hydrogen peroxide topical solution is a weak antibacterial agent, a wound cleanser, and a deodorant. The pharmacologic activity of the drug depends on the release of nascent oxygen which has a powerful oxidizing effect that destroys some microorganisms and chemically alters many organic substances. When hydrogen peroxide topical solution comes in contact with tissues that contain the enzyme catalase, the solution releases oxygen which exerts antibacterial action; the mechanical effect of effervescence loosens tissue debris and pus. The release of nascent oxygen and effervescence is more rapid on wounds, denuded areas, and mucous membranes than on unbroken skin. The presence of reactive organic material such as pus and blood diminishes the efficiency of hydrogen peroxide. The antibacterial activity of hydrogen peroxide is relatively weak and slow and the drug exhibits poor tissue and wound penetration. Hydrogen peroxide's mechanical effect of effervescence and resultant removal of tissue debris is probably a more effective means of reducing the bacterial content of wounds, denuded areas, and mucous membranes than actual antibacterial activity. The drug also appears to have a styptic effect when applied topically to minor wounds. Concentrated solutions of hydrogen peroxide have a bleaching effect on hair and may injure tissue. Increases in the levels of reactive oxygen species (ROS) are correlated with a decrease in calcineurin (CN) activity under oxidative or neuropathological conditions. However, the molecular mechanism underlying this ROS-mediated CN inactivation remains unclear. Here, we describe a mechanism for the inactivation of CN by hydrogen peroxide. The treatment of mouse primary cortical neuron cells with Abeta(1-42) peptide and hydrogen peroxide triggered the proteolytic cleavage of CN and decreased its enzymatic activity. In addition, hydrogen peroxide was found to cleave CN in different types of cells. Calcium influx was not involved in CN inactivation during hydrogen peroxide-mediated cleavage, but CN cleavage was partially blocked by chloroquine, indicating that an unidentified lysosomal protease is probably involved in its hydrogen peroxide-mediated cleavage. Treatment with hydrogen peroxide triggered CN cleavage at a specific sequence within its catalytic domain, and the cleaved form of CN had no enzymatic ability to dephosphorylate nuclear factor in activated T cells. Thus, our findings suggest a molecular mechanism by which hydrogen peroxide inactivates CN by proteolysis in ROS-related diseases. Matrix metalloproteinase-2 (MMP-2) is well known to proteolyse both extracellular and intracellular proteins. Reactive oxygen species activate MMP-2 at both transcriptional and post-translational levels, thus MMP-2 activation is considered an early event in oxidative stress injury. Although hydrogen peroxide is widely used to trigger oxidative stress-induced cell death, the type of cell death (apoptosis vs. necrosis) in cardiomyocytes is still controversial depending on the concentration used and the exposure time. We ... investigated the mode of cell death in neonatal rat cardiomyocytes induced by different concentrations (50-500 uM) of hydrogen peroxide at various time intervals after exposure and determined whether MMP-2 is implicated in hydrogen peroxide-induced cardiomyocyte death. Treating cardiomyocytes with hydrogen peroxide led to elevated MMP-2 level/activity with maximal effects seen at 200 uM. Hydrogen peroxide caused necrotic cell death by disrupting the plasmalemma as evidenced by the release of lactate dehydrogenase in a concentration- and time-dependent manner as well as the necrotic cleavage of PARP-1. The absence o

Pharmacodynamics

Hydrogen peroxide exhibits antimicrobial properties against most forms of microorganisms, including dormant forms with known high resistance profiles, such as bacterial spores and protozoal cysts. It acts as an oxidative biocide to generate free radical species to induce DNA, protein and membrane lipid damage via oxidation.