VIR 102

Indications

• Bacterial infections
• Sepsis
• Pneumonia
• Meningitis
• Endocarditis
• Biliary tract infections
• Prostatitis
• Surgical prophylaxis
• Acute diverticulitis
• Leg ulcer infections

Dosage

Adults: 3–5 mg/kg daily in 3 divided doses, or a single daily dose of 5–7 mg/kg adjusted according to serum-gentamicin concentration. For surgical prophylaxis, 1.5 mg/kg administered intraven

Mechanism of action

Gentamicin exerts its antibacterial effects through a multi-phase mechanism. Initially, it binds to negatively charged components of bacterial cell membranes, increasing membrane permeability. Following this, it enters the bacterial cell via energy-dependent transport mechanisms, where it binds to the 30S ribosomal subunit. This binding causes mistranslation of proteins and disrupts membrane integrity, resulting in bacterial cell death. The action is concentration-dependent, leading to rapid bactericidal effects.

Pharmacodynamics

Gentamicin has a rapid onset of action due to its mechanism of disrupting the bacterial cell membrane and inhibiting protein synthesis. Its effectiveness is enhanced by higher concentrations, and it demonstrates a post-antibiotic effect where bacteria remain suppressed even after drug levels fall below the minimum inhibitory concentration. The drug's efficacy is influenced by factors like the bacterial strain and its susceptibility patterns.

Pharmacokinetics

Gentamicin is usually administered intravenously or intramuscularly. It has a volume of distribution of approximately 0.25 L/kg and is not significantly protein-bound. The drug is primarily eliminated via renal excretion, with a half-life of 2 to 3 hours in individuals with normal renal function. Dosing adjustments are necessary in patients with renal impairment to avoid toxicity. Serum levels should be monitored to optimize therapeutic efficacy while minimizing toxicity.

Contra-indications

• Hypersensitivity to gentamicin or any aminoglycoside
• Severe renal impairment
• Pre-existing auditory or vestibular dysfunction

Adverse effects

• Ototoxicity (hearing loss, vertigo, tinnitus)
• Nephrotoxicity
• Neuromuscular blockade
• Allergic reactions (rash, pruritus)
• Injection site reactions

Interactions

• Gentamicin + relugolix: Unknown (increases exposure)
• Gentamicin + other nephrotoxic drugs (e.g., vancomycin, cisplatin): Increased risk of nephrotoxicity
• Gentamicin + neuromuscular blocking agents: Enhanced neuromuscular blockade

Precautions

• Monitor renal function during therapy, especially in patients with pre-existing renal impairment
• Caution in patients with pre-existing hearing loss or vestibular disorders
• Use with caution in pregnant women and during breastfeeding

Pregnancy

Use only if clearly needed and the benefit justifies the risk to the fetus. Limited data on use in pregnancy.

Breast-feeding

Gentamicin is excreted in breast milk, exercise caution when administering to breastfeeding mothers. Monitor infant for possible side effects.

Storage

Store below 25°C. Protect from light. Do not freeze.

Formulations

• Injection solution (various concentrations)
• Ophthalmic solution (0.3% w/v)
• Topical ointment (0.1% w/v)

Indications

• Measles
• Mumps
• Rubella
• Yellow fever
• Varicella (chickenpox)
• Rotavirus

Dosage

Children: Refer to specific vaccine guidelines for paediatric dosing.

Adults: Refer to specific vaccine guidelines for adult dosing.

Mechanism of action

Attenuated vaccines work by mimicking a natural infection. The weakened pathogen replicates in the body, stimulating the immune system to produce a response against it, which includes the activation of T-cells and the production of antibodies. This prepares the immune system to recognize and fight off the pathogen if exposed in the future.

Pharmacodynamics

The pharmacodynamics of attenuated vaccines involve the interaction of the attenuated pathogen with the host's immune system. Upon administration, the vaccine induces both humoral (antibody-mediated) and cell-mediated immunity. This leads to the development of memory cells that ensure a faster and more effective response upon subsequent exposure to the actual pathogen.

Pharmacokinetics

Attenuated vaccines are generally administered via subcutaneous or intramuscular injection. The pharmacokinetics are characterized by the distribution of the vaccine components within the body, with the attenuated organisms replicating locally and inducing an immune response. The onset of immunity typically occurs within weeks, and the duration of immunity can vary depending on the specific vaccine.

Contra-indications

• Severe immunodeficiency
• Pregnant women (specific live attenuated vaccines)
• Severe allergic reactions to vaccine components

Adverse effects

• Injection site reactions (pain, swelling, redness)
• Low-grade fever
• Malaise
• Rash
• Rare neurological complications (e.g., Guillain-Barré syndrome)

Interactions

• Immunosuppressive agents (may reduce vaccine efficacy)
• Blood products (may interfere with immune response to vaccine)
• Other live vaccines (timing may affect immune response)

Precautions

• History of allergic reactions to previous vaccinations
• Presence of active infections
• Chronic illnesses that may affect immune response

Pregnancy

Live attenuated vaccines are generally contraindicated during pregnancy due to potential risks to the fetus.

Breast-feeding

Most live attenuated vaccines are considered safe during breastfeeding, but caution and consultation with a healthcare provider are advised.

Storage

Store in a refrigerator at 2-8°C. Do not freeze. Protect from light.

Formulations

• Injectable suspension
• Oral suspension
• Lyophilized powder for reconstitution

Indications

• Hypovolemia
• Shock
• Surgery
• Burns

Dosage

Children: Refer to the specific product information or guidelines for paediatric dosage, as it may vary based on the indication and formulation used.

Adults: Refer to the specific product information or guidelines for adult dosage, as it may vary based on the indication and formulation used.

Mechanism of action

Dextran acts as an osmotic agent. When administered intravenously, it increases plasma volume by drawing water into the vascular space. This expansion of blood volume helps in maintaining blood pressure and improving perfusion to tissues.

Pharmacodynamics

The pharmacodynamics of dextran involves its ability to enhance blood flow and reduce blood viscosity. It can improve rheological properties of blood, thereby facilitating better circulation. Dextran's molecular size allows it to remain in the circulation for an extended period, contributing to its volume-expanding effects.

Pharmacokinetics

Dextran is administered intravenously and is distributed in the vascular compartment. Its elimination occurs through renal filtration, and it is eventually degraded by enzymatic action in the liver. The half-life can vary depending on the molecular weight of the dextran used, with larger molecules generally having a longer half-life.

Contra-indications

• Hypersensitivity to dextran or any component of the formulation
• Severe renal impairment
• Congestive heart failure
• Active bleeding or hemorrhagic disorders

Adverse effects

• Allergic reactions, including anaphylaxis
• Fluid overload
• Hypotension
• Headache
• Nausea and vomiting
• Fever
• Thrombocytopenia
• Acute kidney injury

Interactions

• Anticoagulants - may enhance the effects of anticoagulants leading to increased bleeding risk
• Diuretics - may increase the risk of fluid overload and electrolyte imbalances

Precautions

• Use with caution in patients with cardiovascular disease
• Monitor fluid balance closely in patients with renal impairment
• Careful administration in patients with a history of allergic reactions

Pregnancy

Safety during pregnancy has not been established. Use only if clearly needed and potential benefits justify potential risks.

Breast-feeding

Excretion in human milk is unknown. Caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from direct sunlight and moisture. Do not freeze.

Formulations

• Injectable solution for intravenous infusion
• Oral formulations (less common, specific to certain indications)

Indications

• Vascular health
• Oxidative stress-related conditions
• Anti-aging applications
• Inflammatory disorders

Dosage

Children: Refer to the BNF for Children for pediatric dosing information regarding hydrogen-rich water.

Adults: Refer to the BNF for specific dosages and administration guidelines for hydrogen-rich water.

Mechanism of action

Molecular hydrogen exerts its effects primarily through its antioxidant properties, which involve the activation of the Nrf2 pathway. This pathway regulates the expression of various antioxidant enzymes, thereby reducing oxidative stress and inflammation. In endothelial cells, H2 has been shown to prevent TCDD-induced senescence and promote cellular longevity by maintaining cellular homeostasis and modulating redox status.

Pharmacodynamics

The pharmacodynamics of dihydrogen are characterized by its ability to scavenge free radicals and reduce oxidative stress. It also influences cellular signaling pathways related to inflammation and aging. Specifically, H2 aids in maintaining the balance of NAD+/NADH, which is crucial for cellular metabolism and energy production. The modulation of the Nrf2 pathway leads to enhanced production of endogenous antioxidants, contributing to its protective effects on vascular endothelial cells.

Pharmacokinetics

Dihydrogen is rapidly absorbed and distributed in the body. When administered as hydrogen-rich water, it is absorbed through the gastrointestinal tract. Its concentration decreases over time, becoming nearly undetectable after 12 hours in aqueous solutions. The pharmacokinetic profile indicates that the effects of hydrogen may persist even after the gas has been eliminated, likely due to the activation of protective cellular mechanisms.

Pregnancy

There is insufficient data on the use of dihydrogen during pregnancy. Consult a healthcare provider for guidance.

Breast-feeding

Limited information is available regarding the safety of dihydrogen during breastfeeding. Consult a healthcare provider before use.

Storage

Store in a cool, dry place away from direct sunlight. Keep container tightly closed.

Formulations

• Hydrogen-rich water

Indications

• Clinical term 1
• Common term 1
• Clinical term 2
• Common term 2

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing guidelines.

Adults: Refer to the BNF for specific adult dosing guidelines.

Mechanism of action

Dose acts by modulating the activity of specific neurotransmitter receptors and ion channels, influencing various physiological pathways. Its precise mechanism may involve interactions with G-protein coupled receptors, leading to downstream signaling effects that impact cellular responses.

Pharmacodynamics

Dose exhibits a range of effects depending on the dosage and target tissues. It is known to alter neurotransmitter release, affect ion conductance, and influence metabolic pathways, thereby contributing to its therapeutic efficacy and potential side effects.

Pharmacokinetics

Dose is generally absorbed following administration, with peak plasma concentrations occurring within a specified timeframe. Its distribution is influenced by tissue binding and permeability across cell membranes. The drug is metabolized primarily in the liver, with metabolites being excreted via renal and biliary routes. The half-life can vary based on individual patient factors, including age, liver function, and other concurrent medications.

Dosage

Children: Refer to specific guidelines based on the type of fowl and intended use, as dosing is highly variable and specific to the context.

Adults: Refer to specific guidelines based on the type of fowl and intended use, as dosing is highly variable and specific to the context.

Pregnancy

Not applicable.

Breast-feeding

Not applicable.

Storage

Store in a cool, dry place away from direct sunlight.

Indications

• Lactose intolerance
• As a filler or excipient in pharmaceutical formulations

Dosage

Children: Refer to the BNF for Children for specific dosing information based on age and clinical context.

Adults: Refer to the BNF for specific dosing information based on clinical context.

Mechanism of action

Lactose is metabolized in the intestine by the enzyme lactase into its constituent monosaccharides, glucose and galactose. In individuals with lactase deficiency, unabsorbed lactose passes into the colon, where it is fermented by bacteria, leading to gas production and osmotic effects that contribute to diarrhea.

Pharmacodynamics

The pharmacodynamics of lactose are primarily related to its effects on gastrointestinal function. In healthy individuals, lactose is effectively broken down into glucose and galactose, which are absorbed and utilized for energy. In individuals with lactose intolerance, the unabsorbed lactose can cause osmotic diarrhea and colonic fermentation, leading to discomfort and symptoms associated with lactose intolerance.

Pharmacokinetics

Lactose is not absorbed in the gastrointestinal tract until it is hydrolyzed into glucose and galactose by lactase. The absorption of glucose and galactose occurs in the small intestine. The half-life is not applicable as lactose is not typically administered as a medication but is rather ingested as a natural component of food. Its metabolism primarily occurs in the intestine.

Adverse effects

• Bloating
• Diarrhea
• Abdominal pain
• Flatulence

Precautions

• Use with caution in patients with lactose intolerance.
• Consider potential for gastrointestinal upset in sensitive individuals.

Pregnancy

Lactose is generally considered safe for use during pregnancy. However, consult a healthcare professional for individual advice.

Breast-feeding

Lactose is safe to use while breastfeeding, as it is a natural sugar present in breast milk.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Powder
• Granules
• Tablets
• Syrup

Indications

• Measles
• Mumps
• Rubella
• Varicella (chickenpox)
• Yellow fever
• Rotavirus
• Intranasal influenza

Dosage

Children: Refer to the BNF for Children for specific dosing information based on age and vaccine type.

Adults: Refer to specific product guidelines for dosing information, as it can vary by vaccine type and brand.

Mechanism of action

Live vaccines work by introducing a weakened or attenuated form of a pathogen into the body. This stimulates the immune system to recognize and respond to the pathogen, leading to the production of antibodies and memory cells that provide long-term protection against future infections by the same pathogen.

Pharmacodynamics

The pharmacodynamics of live vaccines involve the activation of both humoral and cellular immunity. Following vaccination, the immune system generates a robust response, including the production of specific antibodies and the activation of T cells that can recognize and eliminate infected cells. This dual action helps establish long-term immunity.

Pharmacokinetics

The pharmacokinetics of live vaccines vary depending on the specific vaccine. Generally, the vaccine is administered via injection, allowing the live attenuated organisms to enter the bloodstream. The immune response typically begins within days and can last for years, depending on the vaccine. Live vaccines are usually stored under refrigeration to maintain their viability, and they should be administered within their expiration dates.

Interactions

• livevaccines + abrocitinib: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + baricitinib: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + filgotinib: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + dexrazoxane: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + iron chelators: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + ozanimod: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + ponesimod: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + siponimod: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + upadacitinib: Severe (increases risk of generalised infection (possibly life-threatening))
• livevaccines + diroximelfumarate: Moderate (increases risk of generalised infection (possibly life-threatening))

Indications

• Bacterial infections
• Pneumonia
• Streptococcal infections
• Syphilis
• Meningitis
• Endocarditis
• Skin infections

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on the type of penicillin and indication.

Adults: Refer to the BNF for specific dosing recommendations based on the type of penicillin and indication.

Mechanism of action

Penicillin targets penicillin-binding proteins (PBPs) located inside the bacterial cell wall. By binding to these proteins, penicillin disrupts the transpeptidation process, which is essential for cell wall structural integrity. This results in weakened cell walls, causing osmotic instability and ultimately leading to cell lysis and death.

Pharmacodynamics

Penicillin exhibits bactericidal activity, meaning that it kills bacteria rather than merely inhibiting their growth. Its effectiveness is generally dependent on the growth phase of the bacteria, as it is most active against actively dividing cells. The spectrum of activity varies among different penicillins, with some being more effective against specific bacterial strains.

Pharmacokinetics

Penicillin is primarily absorbed in the gastrointestinal tract, with its bioavailability varying depending on the specific type of penicillin. It is primarily excreted by the kidneys, with a half-life that typically ranges from 30 minutes to 2 hours, depending on the formulation. Dosage adjustments may be necessary in patients with renal impairment to prevent accumulation and toxicity.

Contra-indications

• History of hypersensitivity to penicillins
• Severe allergic reactions to beta-lactam antibiotics

Adverse effects

• Allergic reactions such as rash, urticaria, and anaphylaxis
• Gastrointestinal disturbances including nausea, vomiting, and diarrhea
• Superinfection due to alteration of normal flora
• Hematologic reactions such as leukopenia, thrombocytopenia

Interactions

• valproate+penicillins: Severe (increases risk of adverse effects)
• allopurinol+penicillins: Unknown (increases risk of skin rash)
• leflunomide+penicillins: Unknown (increases exposure)
• nitisinone+penicillins: Unknown (increases exposure)
• penicillins+phenindione: Unknown (increases risk of bleeding events)
• teriflunomide+penicillins: Unknown (increases exposure)

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of allergic reactions
• Consider alternative therapy in patients with a history of severe allergies

Pregnancy

Penicillins are generally considered safe to use during pregnancy; however, consult local guidelines and assess benefits versus risks.

Breast-feeding

Penicillins are excreted in breast milk in small amounts; generally considered safe, but monitor infant for possible effects.

Storage

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

Formulations

• Oral tablets
• Oral suspension
• Intravenous injection
• Intramuscular injection

Indications

• Bacterial infections
• Viral infections
• Epidemiological studies
• Antibiotic resistance monitoring

Dosage

Children: Refer to specific antimicrobial treatment guidelines based on the strain identified and the infection site.

Adults: Refer to specific antimicrobial treatment guidelines based on the strain identified and the infection site.

Mechanism of action

The mechanism of action for a strain depends on the type of microorganism it represents. For pathogenic bacteria, the strain may produce toxins, evade the host's immune response, or possess resistance mechanisms that allow it to survive in the presence of antibiotics. For viruses, strains may exhibit mutations that alter their ability to infect host cells or evade antiviral therapies.

Pharmacodynamics

Pharmacodynamics in the context of strains involves the interaction between the strain and the host's immune system, as well as the effects of specific antimicrobial agents on the strain. These interactions can influence the efficacy of treatments and the development of resistance.

Pharmacokinetics

Pharmacokinetics is not directly applicable to strains themselves but rather to the drugs used to treat infections caused by specific strains. Factors such as absorption, distribution, metabolism, and excretion of antimicrobial agents can vary depending on the strain's characteristics and the site of infection.

Pregnancy

There is limited information on the safety of strain in pregnancy. It is advisable to consult healthcare professionals for guidance.

Breast-feeding

Safety during breastfeeding is not well established. It is recommended to seek medical advice before use.

Storage

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

Indications

• Influenza
• HIV/AIDS
• Hepatitis B and C
• Herpes simplex virus infections
• Cytomegalovirus infections
• COVID-19
• Respiratory syncytial virus infections

Dosage

Children: Refer to specific antiviral agents for dosing guidance.

Adults: Refer to specific antiviral agents for dosing guidance.

Mechanism of action

Viruses infect host cells by attaching to specific receptors on the cell surface. Once inside, they hijack the host cell's machinery to replicate their genetic material and produce viral proteins. New viral particles are assembled and released from the host cell, often destroying the cell in the process. The specific mechanism can vary depending on the virus type, including integration into the host genome in retroviruses or utilizing specific pathways for replication.

Pharmacodynamics

The pharmacodynamics of antiviral agents depend on the specific virus and the mechanism of action. Antiviral drugs may inhibit viral entry into host cells, block viral replication, or prevent the assembly of new virions. The effectiveness of antiviral therapy often relates to the stage of viral replication and the immune response of the host.

Pharmacokinetics

Pharmacokinetics of antiviral drugs varies widely based on the specific medication used. Generally, antiviral agents are absorbed through the gastrointestinal tract and distributed throughout the body. They may undergo hepatic metabolism and are often excreted through the kidneys. The half-life of these drugs can range from a few hours to several days, influencing dosing schedules.

Mechanism of action

There are 3 key phases of aminoglycoside entry into cells. The first “ionic binding phase” occurs when polycationic aminoglycosides bind electrostatically to negatively charged components of bacterial cell membranes including with lipopolysaccharides and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acids and phospholipids within the cell membrane of Gram-positive bacteria. This binding results in displacement of divalent cations and increased membrane permeability, allowing for aminoglycoside entry. The second “energy-dependent phase I” of aminoglycoside entry into the cytoplasm relies on the proton-motive force and allows a limited amount of aminoglycoside access to its primary intracellular target - the bacterial 30S ribosome. This ultimately results in the mistranslation of proteins and disruption of the cytoplasmic membrane. Finally, in the “energy-dependent phase II” stage, concentration-dependent bacterial killing is observed. Aminoglycoside rapidly accumulates in the cell due to the damaged cytoplasmic membrane, and protein mistranslation and synthesis inhibition is amplified. The necessity of oxygen-dependent active transport explains why aminoglycosides are ineffective against anaerobic bacteria. Hence, aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modeling support this two-mechanism model. Inhibition of protein synthesis is a key component of aminoglycoside efficacy. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site. Overall, aminoglycoside binding has several negative effects including inhibition of translation, initiation, elongation, and ribosome recycling. Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit. Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation. Mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above. Aminoglycosides are usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/ ... Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. ... /Aminoglycosides/

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