Lacoma

Indications

• Raised intraocular pressure in open-angle glaucoma
• Ocular hypertension

Dosage

Children: Child: Apply once daily, to be administered preferably in the evening.

Adults: Apply once daily, preferably in the evening.

Mechanism of action

Latanoprost selectively stimulates the prostaglandin F2 alpha receptor, leading to increased outflow of aqueous humor. This mechanism involves remodeling the extracellular matrix and regulating matrix metalloproteinases, which enhances tissue permeability and modifies outflow resistance, thus decreasing intraocular pressure (IOP).

Pharmacodynamics

Latanoprost effectively reduces intraocular pressure by enhancing uveoscleral outflow. The onset of action occurs within 3 to 4 hours, reaching its maximum effect at 8 to 12 hours post-administration, with activity maintained for approximately 24 hours. Notably, long-term use may cause changes in iris pigmentation and other ocular effects such as conjunctival hyperemia and eyelash changes in a small proportion of patients.

Pharmacokinetics

Latanoprost is administered as eye drops and is absorbed through the cornea. It undergoes hydrolysis to its active form, which then exerts its therapeutic effects. The drug's effects are most pronounced within the first 12 hours after administration, with a duration of action that supports once-daily dosing. It is important to note that the presence of benzalkonium chloride in some formulations may cause ocular irritation.

Contra-indications

• Active herpes simplex keratitis
• History of recurrent herpetic keratitis associated with prostaglandin analogues

Adverse effects

• Iris pigmentation
• Conjunctival hyperemia
• Pigmentation of periocular tissues
• Eyelash changes
• Hypertrichosis
• Ocular irritation
• Dizziness
• Headache
• Myalgia
• Chest pain
• Dyspnoea
• Unstable angina

Interactions

• May interact with thiomersal-containing preparations
• Use with caution in patients receiving other ocular medications

Precautions

• Do not use within 5 minutes of thiomersal-containing preparations
• Monitor patients with a history of significant asthma
• Use with caution in patients with angle-closure glaucoma or aphakia
• Consider risks for uveitis in predisposed individuals

Pregnancy

Manufacturer advises to avoid use during pregnancy due to potential effects.

Breast-feeding

May be present in breast milk; manufacturer advises caution.

Storage

Store at room temperature. Protect from light. Once opened, use within a specified time frame as indicated by the manufacturer.

Formulations

• Latanoprost 50 microgram per 1 ml eye drops
• Monopost 50 micrograms/ml eye drops
• Medizol 50 micrograms/ml eye drops
• Xalatan 50 micrograms/ml eye drops

Indications

• Seborrhoeic dermatitis
• Dandruff
• Scalp psoriasis
• Bacterial infections affecting the scalp

Dosage

Children: For children, apply 3 times a week for 1 week, then apply twice weekly as needed. Refer to BNF for Children for further details.

Adults: Apply to the affected area as directed, typically 1-3 times weekly depending on the condition being treated. Refer to specific product guidelines for detailed dosing.

Mechanism of action

Benzalkonium chloride exerts its antimicrobial effect by disrupting the cell membrane of microorganisms, leading to leakage of cellular contents and ultimately cell death. This is facilitated by its cationic nature, which allows it to bind to negatively charged bacterial surfaces.

Pharmacodynamics

Benzalkonium chloride demonstrates rapid bactericidal activity, with effectiveness observed against gram-positive and gram-negative bacteria, fungi, and some viruses. Its antiseptic properties may be enhanced in the presence of moisture and are typically influenced by the concentration of the solution used.

Pharmacokinetics

Benzalkonium chloride is poorly absorbed through the skin. After topical application, it remains primarily at the site of application, where it exerts localized effects. Systemic absorption is minimal, and it is primarily eliminated through the skin and urine. However, specific pharmacokinetic data may vary based on formulation and application site.

Pregnancy

Benzalkonium chloride should be used with caution during pregnancy. Refer to specific guidelines or consult a healthcare professional.

Breast-feeding

Benzalkonium chloride should be used with caution while breastfeeding. Refer to specific guidelines or consult a healthcare professional.

Storage

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

Formulations

• Shampoo
• Soap or detergent
• Topical solution

Indications

• Disinfection of surfaces
• Antiseptic for skin
• Preservative in pharmaceuticals
• Treatment of minor cuts and abrasions

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations in pediatric populations.

Adults: Refer to the BNF for specific formulations and concentrations as doses may vary based on the application and preparation.

Mechanism of action

The bactericidal action of benzalkonium chloride is believed to result from the disruption of intermolecular interactions, which leads to the dissociation of cellular membrane lipid bilayers in bacteria. This disruption compromises cellular permeability, causing leakage of vital cellular contents. Moreover, the agent can deactivate important molecular complexes such as enzymes that regulate various respiratory and metabolic activities within the cells. Cationic surfactants like benzalkonium chloride can thus effectively disrupt critical intermolecular interactions and tertiary structures in biochemical systems, impairing bacterial function.

Pharmacodynamics

Benzalkonium chloride is classified as a biocidal agent with a relatively long duration of action. It exhibits a spectrum of activity against various microorganisms, including bacteria, certain viruses, fungi, and protozoa; however, it is ineffective against bacterial spores. The agent tends to demonstrate greater efficacy against gram-positive bacteria compared to gram-negative ones. The mode of action can be bacteriostatic (preventing growth) or bactericidal (killing bacteria), depending on its concentration. The activity of benzalkonium chloride is generally stable across different pH levels but is enhanced at elevated temperatures and with extended exposure.

Pharmacokinetics

The pharmacokinetic properties of benzalkonium chloride, including absorption, distribution, metabolism, and excretion, are not fully characterized. Its topical application limits systemic exposure, and it primarily exerts localized effects at the site of application. The duration of action and efficacy may be influenced by the formulation and concentration used.

Pregnancy

Benzalkonium chloride is generally considered safe for use during pregnancy when applied topically, but systemic absorption should be minimized. Always consult a healthcare provider for use during pregnancy.

Breast-feeding

Benzalkonium chloride is considered safe for topical application during breastfeeding, but care should be taken to avoid exposure to the infant. Consultation with a healthcare provider is recommended.

Storage

Store at room temperature, away from moisture and heat. Keep in a tightly closed container, protected from light.

Formulations

• Topical solution
• Disinfectant wipes
• Liquid antiseptics

Indications

• Constipation
• Labor induction
• Topical treatment for skin conditions

Dosage

Children: Refer to the BNF for Children for appropriate pediatric dosing guidelines, as no specific doses are provided.

Adults: Refer to specific guidelines for adult dosing based on the formulation used and the condition being treated, as no standardized dose is provided.

Mechanism of action

Ricinoleic acid, the main active component of castor oil, acts as a stimulant laxative. It works by increasing the peristaltic movement of the intestines, which aids in the evacuation of stool. Additionally, it may inhibit the absorption of water in the intestines, resulting in softer stools. The oil is also believed to have anti-inflammatory properties, which can be beneficial in treating certain skin conditions.

Pharmacodynamics

The pharmacodynamic properties of castor oil include its ability to stimulate intestinal motility and increase the secretion of intestinal fluids. This leads to a faster transit time for stool through the bowel. In topical applications, castor oil exhibits emollient and moisturizing effects, promoting healing and soothing irritated skin. Its anti-inflammatory effects may also contribute to the reduction of swelling and pain in inflamed tissues.

Pharmacokinetics

Castor oil is absorbed in the gastrointestinal tract, where it is metabolized to ricinoleic acid. The onset of action for its laxative effect typically occurs within 2 to 6 hours after oral administration. The duration of action varies, but effects usually last for several hours. When applied topically, castor oil penetrates the skin and may provide localized effects without significant systemic absorption.

Adverse effects

• Abdominal cramps
• Diarrhea
• Nausea
• Vomiting
• Dehydration

Precautions

• Use with caution in patients with gastrointestinal disorders
• Not recommended for prolonged use
• Monitor for signs of dehydration

Pregnancy

Castor oil is generally not recommended during pregnancy due to potential uterine contractions and risk of premature labor.

Breast-feeding

Castor oil should be used with caution during breastfeeding as it may cause gastrointestinal discomfort in nursing infants.

Storage

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

Formulations

• Liquid
• Capsules

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

• Electrolyte replacement
• Volume expansion in hypovolemic patients
• Management of hyponatremia
• Support in intravenous fluid therapy

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients, as dosages may vary based on the formulation and clinical condition.

Adults: Refer to specific product information or clinical guidelines for dosage recommendations, as disodium is often part of combination products.

Mechanism of action

Disodium compounds often function by providing sodium ions that are essential for various physiological processes. Sodium ions play a critical role in maintaining osmotic balance, nerve impulse transmission, and muscle contraction. In the context of intravenous solutions, disodium helps to restore electrolyte balance in patients.

Pharmacodynamics

The pharmacodynamics of disodium is primarily related to its role in electrolyte balance and fluid homeostasis. Sodium ions are vital for the function of excitable tissues, including neurons and muscle cells. Changes in sodium levels can affect blood pressure, hydration status, and overall cellular function.

Pharmacokinetics

The pharmacokinetics of disodium compounds depend on their specific formulation and route of administration. When administered intravenously, disodium is rapidly distributed in the extracellular fluid, where it helps to maintain osmotic pressure. Sodium is primarily excreted by the kidneys, and its levels can be influenced by fluid intake, dietary sodium, and renal function.

Pregnancy

Use with caution. Consult a healthcare provider for specific guidance.

Breast-feeding

Use with caution. Consult a healthcare provider for specific guidance.

Storage

Store at room temperature, away from moisture and direct sunlight.

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

Dosage

Children: Paediatric dosing information is not standardized and should be derived from specific product guidelines or expert consultation.

Adults: Dosage and usage depend on the specific hydrogenated compound and its intended therapeutic application. Refer to specific product guidelines for detailed dosing information.

Mechanism of action

Hydrogenation alters the molecular structure of fatty acids, transforming double bonds into single bonds. This process increases the saturation level of fats, which can influence their metabolic pathways and lipid profiles in the body.

Pharmacodynamics

The pharmacodynamic effects of hydrogenated compounds depend on the specific substance being hydrogenated. Generally, hydrogenated fats can affect lipid metabolism, potentially leading to increased levels of LDL cholesterol and decreased levels of HDL cholesterol when consumed in excess. The physiological effects may include changes in insulin sensitivity and inflammatory responses.

Pharmacokinetics

The pharmacokinetics of hydrogenated compounds vary widely based on the specific hydrogenated product. Generally, these compounds are absorbed in the gastrointestinal tract, where they may undergo further metabolism by enzymes. The bioavailability, distribution, metabolism, and excretion depend on the fatty acid composition and the presence of other dietary components.

Pregnancy

Hydrogenated compounds, depending on their specific type, may have varying safety profiles in pregnancy. It is essential to consult specific guidelines or studies related to the particular hydrogenated substance in question.

Breast-feeding

The safety of hydrogenated compounds during breastfeeding may vary. Consultation with healthcare professionals regarding specific substances is advisable.

Storage

Hydrogenated substances should be stored in a cool, dry place, away from direct sunlight and heat to maintain stability.

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

• Pain management
• Vaccination
• Antibiotic therapy
• Hormonal therapies
• Anesthesia
• Nutritional support
• Chemotherapy

Dosage

Children: Refer to specific drug guidelines for paediatric dosing, as it requires careful consideration of weight and age.

Adults: Refer to specific drug guidelines for adult dosing, as it varies widely depending on the medication and clinical condition.

Mechanism of action

The mechanism of action of injected drugs varies widely based on the specific medication being administered. Generally, injected drugs enter the bloodstream directly, allowing them to circulate rapidly throughout the body. For instance, antibiotics may work by inhibiting bacterial cell wall synthesis, while analgesics may modulate pain pathways in the central nervous system. Each drug has unique pathways through which it achieves its therapeutic effects.

Pharmacodynamics

Pharmacodynamics refers to the effects of drugs on the body and their mechanisms of action. For injectable medications, effects can be immediate or delayed, depending on the drug's formulation and route of administration. Factors influencing pharmacodynamics include receptor affinity, drug concentration, and the presence of other substances that may enhance or inhibit the drug's effects. For example, some injectable drugs may require specific receptors to exert their effects, while others may have a broader range of action.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of injected drugs. After administration, drugs are rapidly absorbed into the bloodstream, leading to quick therapeutic effects. The distribution depends on factors such as blood flow, tissue permeability, and protein binding. Drugs are metabolized primarily in the liver and excreted through the kidneys or bile. The pharmacokinetic profile can vary widely based on the drug's chemical nature, dosage, and individual patient factors.

Pregnancy

Safety during pregnancy depends on the specific injection and its active ingredients. It is essential to consult a healthcare professional for guidance.

Breast-feeding

The safety of injections during breastfeeding varies by the specific medication. It is recommended to seek advice from a healthcare provider.

Storage

Store injections as per manufacturer's guidelines, usually in a cool, dry place away from direct sunlight. Some may require refrigeration.

Indications

• Constipation
• Bowel preparation before colonoscopy or surgery

Dosage

Children: Refer to specific product guidelines for dosing instructions.

Adults: Refer to specific product guidelines for dosing instructions.

Mechanism of action

Polyoxyl works by retaining water in the stool, increasing its bulk and consistency. This osmotic effect stimulates bowel movements by softening the stool and promoting peristalsis. The water-retaining properties are attributed to its high molecular weight and hydrophilicity, which allow it to attract and hold water within the gastrointestinal tract.

Pharmacodynamics

The pharmacodynamic profile of polyoxyl includes its ability to enhance stool water content, thereby improving fecal passage through the intestines. This results in increased stool frequency and decreased transit time. Polyoxyl does not significantly affect electrolyte balance, making it a safe option for chronic constipation management.

Pharmacokinetics

Polyoxyl is not absorbed systemically; it remains in the gastrointestinal tract where it exerts its effects. The onset of action can vary but typically occurs within 24 to 72 hours after administration. The elimination of polyoxyl occurs through fecal excretion, with no significant metabolism or renal clearance involved.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal cramps
• Allergic reactions

Precautions

• Use with caution in patients with gastrointestinal disorders.
• Monitor for allergic reactions in patients with a history of hypersensitivity.

Pregnancy

Polyoxyl is generally regarded as safe for use during pregnancy, but specific clinical guidance should be consulted.

Breast-feeding

Polyoxyl is considered safe during breastfeeding, though maternal factors should be assessed.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Oral solution
• Tablet
• Topical cream

Mechanism of action

Elevated intraocular pressure leads to an increased risk of glaucomatous visual field loss. The higher the intraocular pressure, the higher the risk of damage to the optic nerve and loss of visual field. Latanoprost selectively stimulates the prostaglandin F2 alpha receptor and this results in a decreased intraocular pressure (IOP) via the increased outflow of aqueous humor, which is often implicated in cases of elevated intraocular pressure. Possible specific mechanisms of the abovementioned increased aqueous outflow are the remodeling of the extracellular matrix and regulation of matrix metalloproteinases. These actions result in higher tissue permeability related to humor outflow pathways, which likely change outflow resistance and/or outflow rates.

Pharmacodynamics

Latanoprost effectively decreases intraocular pressure by increasing uveoscleral outflow. A decrease in intraocular pressure has been measured within 3–4 hours post-administration, reaches a maximum decrease at 8–12 hours, and can be maintained for a period of 24 hours. **A note on eye and periorbital changes** Between 3 to 10% of patients taking latanoprost have experienced iris pigmentation after about 3-4 months of latanoprost use. Patients should be notified of this risk before initiating treatment. It may occur in both patients with light-colored irides (green-brown or blue/grey-brown) or dark-colored (brown) irides, but is less pronounced in the latter group. This drug may also cause other ocular effects including infrequent conjunctival hyperemia, pigmentation of periocular tissues, eyelash changes, hypertrichosis, and ocular irritation.

Mechanism of action

Although not entirely elucidated, the bactericidal action of benzalkonium chloride is believed to be due to the disruption of intermolecular interactions. Such disruption can cause the dissociation of cellular membrane lipid bilayers of bacteria, resulting in compromised cellular permeability control and the leakage of important cellular contents. Additionally, other important molecular complexes like enzymes which control the maintenance of a great range of respiratory and metabolic cellular activities, are also susceptible to such deactivation. Consequently, a variety of critical intermolecular interactions and tertiary structures in very highly specific biochemical systems that allow bacterial agents to function normally can be readily disrupted or deactivated by cationic surfactants like benzalkonium chloride..

Pharmacodynamics

Benzalkonium chloride solutions are generally categorized as biocidal agents with relative long durations of action. Their spectrum of activity has been demonstrated against bacteria, to some viruses, fungi, and protozoa, although bacterial spores are treated as being resistant to the agent. Additionally, the agent generally shows more activity against gram-positive than gram-negative bacteria. Finally, solutions of benzalkonium chloride are bacteriostatic or bactericidal based on their concentration. Bacteriostatic agents act to prevent further growth of bacterial organisms that are present while bactericidal agents function to kill bacteria that are present. In general, the activity of the agent is not largely affected by pH, but such activity does increase substantially at higher temperatures and prolonged exposure times.

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

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