Risk assessment to human health: Consumer exposure to ingredients in air fresheners.

Ingredient chemicals like fragrances may cause adverse health effects. Frequent health risk assessments and stringent management of consumer products are of paramount importance to reduce these serious occurrences. In this study, the respiratory and dermal health effects were assessed in relation to air fresheners. Twenty six fragrance ingredients, thirty four biocidal ingredients, and sixteen hazardous ingredients were analyzed and assessed according to their risk to human health on five groups by application type in eighty two air fresheners. For hazard characterization of ingredients, toxicological information on the intrinsic properties of the ingredients was collected, and reference values were determined as chronic NOAEL. Exposure assessment was performed in two steps. The 95th exposure factor values were used to estimate exposure to assume the worst-case scenario and the maximum concentration determined by the product purpose and application type was used type in tiered 1 assessment. The values input into the exposure algorithms were developed via the exposure route. In the tiered 2 assessment, the 75th exposure factor values were used to estimate the assumed reasonable exposure to ingredients. Six ingredients for the inhalation and twelve ingredients for the dermal route were conducted for tiered 2 assessment. This study showed that the assessed ingredients have no health risks at their maximum concentrations in air fresheners. The approach should be used to establish improved guidelines for specific ingredients that may pose inhalation and dermal hazard.

Fat deposition in the tunica muscularis and decrease of interstitial cells of Cajal and nNOS-positive neuronal cells in the aged rat colon.

Little is known about the time course of aging on interstitial cells of Cajal (ICC) of colon. The aim of this study was to investigate the change of morphology, ICC, and neuronal nitric oxide synthase (nNOS)-immunoreactive cells in the aged rat. The proximal colon of 344 Fischer rats at four different ages (6, 31, 74 wk, and 2 yr) were studied. The immunoreactivity of c-Kit, nNOS, anti-protein gene product 9.5, and synaptophysin were counted after immunohistochemistry. The c-kit, stem cell factor (ligand of Kit), and nNOS mRNA were measured by real-time PCR. c-Kit and nNOS protein were assessed by Western blot. Isovolumetric contractile force measurement and electrical field stimulation (EFS) were conducted. The area of intramuscular fat deposition significantly increased with age after 31 wk. c-Kit-immunoreactive ICC and nNOS-immunoreactive neurons and nerve fibers significantly declined with age. mRNA and protein expression of c-kit and nNOS decreased with aging. The functional study showed that the spontaneous contractility was decreased in aged rat, whereas EFS responses in the presence of atropine and L-NG-Nitroarginine methyl ester were increased in aged rat. In conclusion, the decrease of proportion of proper smooth muscle, the density of ICC and nNOS-immunoreactive neuronal fibers, and the number of nNOS-immunoreactive neurons during the aging process may explain the aging-associated colonic dysmotility.

Evaluation of inhalation risk during quarantine work with quaternary ammonium compounds-based disinfectant.

Quarantine work is widely recognized as an indispensable endeavor in curbing the propagation of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Furthermore, the heavy workload places workers at a heightened risk of chemical exposure and respiratory damage. Consequently, it is paramount to systematically perform health risk assessments and meticulously oversee the work by wearing personal protective equipment to minimize these risks. To assess the inhalation exposure, this study examined data on disinfectant exposure from quarantine professional users who utilized disinfectants containing quaternary ammonium compounds. Through a survey of 6,199 cases conducted by 300 quarantine professional users who actively engaged in quarantine work, we assembled a database of exposure factors derived from their utilization of spray-type disinfectants for quarantine purposes. Based on these data, we formulated an inhalation exposure algorithm, which considers the time-weighted average (TWA) air concentrations. The test results demonstrated that the industrial-grade respirator mask could prevent a minimum of 68.3 % of particles, reducing respiratory exposure. Consequently, the hazard quotient (HQ) due to disinfectant exposure also decreased. This research is essential in safeguarding the safety and health of professional users engaged in quarantine-related tasks. By implementing strict measures like health risk assessments and personal protective equipment, individuals with quarantine experience can safely carry out their quarantine work. The results of this study are expected to serve as a framework for improving policies and regulations concerning quarantine work and safeguarding the health of professional users.

Fisetin inhibits matrix metalloproteinases and reduces tumor cell invasiveness and endothelial cell tube formation.

Matrix metalloproteinases (MMPs) play an important role in tissue remodeling during normal physiological situations and pathological implications such as tumor invasion and metastasis. MMP inhibitors were screened from extracts of medicinal herbs by an enzymatic assay using the MMP-14 catalytic domain. Among samples tested, a methanol extract of the root of Dalbergia odorifera T. CHEN (Leguminosae) showed the strongest inhibitory activity. The inhibitory component was purified through fractionation methods and identified as fisetin, abundant in many fruits and vegetables. In addition to inhibition of MMP-14, fisetin inhibits MMP-1, MMP-3, MMP-7, and MMP-9, more efficiently than a naturally occurring MMP inhibitor tetracycline. Fisetin dose-dependently inhibits proliferation of fibrosarcoma HT-1080 cells and human umbilical vascular endothelial cells (HUVECs), MMP-14-mediated activation of proMMP-2 in HT-1080 cells, invasiveness of HT-1080 cells, and in vitro tube formation of HUVECs. Therefore, fisetin could be valuable as a chemopreventive agent against cancer and a lead compound for development of therapeutic MMP inhibitors.

Effect of aging on gastric mucosal defense mechanisms: ROS, apoptosis, angiogenesis, and sensory neurons.

Aging changes in the stomach lead to a decreased capacity for tissue repair in response to gastric acid. The aim of this study was to determine the mechanism associated with the increased susceptibility to injury of aging mucosa including reactive oxygen species (5), apoptosis, angiogenesis, and sensory neuron activity. Fischer 344 rats at four different ages (6, 31, 74 wk, and 2 yr of age) were studied. The connective tissue indicators [salt-soluble collagen and sulfated glycosaminoglycan (sGAG)], lipid hydroperoxide (LPO), myeloperoxidase (MPO), and hexosamine were assessed. We also evaluated the expression of early growth response-1 (Egr-1), phosphatase and tension homologue deleted on chromosome 10 (PTEN), caspase-9 (index of apoptosis), VEGF (index of angiogenesis), calcitonin gene-related peptide (CGRP, index of sensory neurons), and neuronal nitric oxide synthase (nNOS). The histological connective tissue area in the lower part of rat gastric mucosa increased with aging, with increase of salt-soluble collagen and sGAG. LPO and MPO in old rats were significantly greater than in the young rats, whereas hexosamine was significantly reduced. The old gastric mucosa had increased expression of Egr-1, PTEN, and caspase-9, whereas the VEGF, CGRP, and nNOS expression were significantly reduced. These results indicate that the lower part of rat gastric mucosa was found to be replaced by connective tissue with accumulation of oxidative products with aging. In addition, impairment of apoptosis, angiogenesis, and sensory neuron activity via the activation of Egr-1 and PTEN might increase the susceptibility of gastric mucosa to injury during aging.

Anti-inflammatory and analgesic activities of SKLJI, a highly purified and injectable herbal extract of Lonicera japonica.

The parenteral route has many merits over the oral route, including greater predictability, reproducibility of absorption, and rapid drug action, but injectable phytomedicines are uncommon due to protein precipitating tannin and hemolytic saponin components. In this study, in an effort to develop a safe injectable analgesic phytomedicine, we prepared a tannin and saponin-free Lonicera japonica extract, SKLJI, through fractionation and column purification, and evaluated its anti-inflammatory and analgesic activities in in vivo experimental models of inflammation and pain. The removal of tannin and saponin resulted in loganin and sweroside-enriched SKLJI and it showed reduced hemolysis and protein precipitation. In efficacy tests, SKLJI inhibited croton oil- and arachidonic acid-induced ear edema, acetic acid-induced writhing, and carrageenan-induced rat hind paw hyperalgesia. Inhibition of cylcooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and 5-lipoxyfenase (5-LO) activities by SKLJI appeared to be the mechanism underlying anti-inflammatory and analgesic efficacy. Loganin and sweroside also showed anti-inflammatory and analgesic activities, suggesting that they might be active principles in the efficacy of SKLJI. These results suggest that SKLJI is a viable candidate for a new anti-inflammatory and analgesic phytomedicine that can be administered by the parenteral route.

Enhancement of gastric ulcer healing and angiogenesis by cochinchina Momordica seed extract in rats.

Cochinchina momordica seed is the dried ripe seed of Momordica cochinchinensis, a perennial vine. The antiulcer effect of an extract from cochinchina momordica seeds (SK-MS10) was evaluated in a rat model of acetic acid-induced gastric ulcers. Gastric ulcers were produced by subserosal injection of acetic acid. SK-MS10 (200 mg/kg) or vehicle was administered orally once per day for 14 days after the acetic acid injection. The stomach was removed and the ulcer size measured at day 7 and 14 of the treatment. Expression of vascular endothelial growth factor (VEGF) was assessed by real-time RT-PCR and Western blot analysis. In addition, the microvasculature density (MVD) adjacent to the ulcer margin was examined by immunohistochemistry. The treatment with SK-MS10 for 7 and 14 days significantly accelerated ulcer healing and increased the expression of mRNA (at day 7) as well as VEGF protein (at day 14) compared to the vehicle-treated rats. The MVD for factor VIII was also higher in the SK-MS10 treatment group compared to the vehicle-treated rats; however, these differences were not statistically significant. These results suggest that SK-MS10 treatment accelerates the healing of gastric ulcers via upregulation of VEGF and angiogenesis in an acetic acid rat model.

A Potential Health Risk to Occupational User from Exposure to Biocidal Active Chemicals.

Biocidal active chemicals have potential health risks associated with exposure to retail biocide products such as disinfectants for COVID-19. Reliable exposure assessment was investigated to understand the exposure pattern of biocidal products used by occupational workers in their place of occupation, multi-use facilities, and general facilities. The interview-survey approach was taken to obtain the database about several subcategories of twelve occupational groups, the use pattern, and the exposure information of non-human hygiene disinfectant and insecticide products in workplaces. Furthermore, we investigated valuable exposure factors, e.g., the patterns of use, exposure routes, and quantifying potential hazardous chemical intake, on biocidal active ingredients. We focused on biocidal active-ingredient exposure from products used by twelve occupational worker groups. The 685 non-human hygiene disinfectants and 763 insecticides identified contained 152 and 97 different active-ingredient chemicals, respectively. The toxicity values and clinical health effects of total twelve ingredient chemicals were determined through a brief overview of toxicity studies aimed at estimating human health risks. To estimate actual exposure amounts divided by twelve occupational groups, the time spent to apply the products was investigated from the beginning to end of the product use. This study investigated the exposure assessment of occupational exposure to biocidal products used in workplaces, multi-use facilities, and general facilities. Furthermore, this study provides valuable information on occupational exposure that may be useful to conduct accurate exposure assessment and to manage products used for quarantine in general facilities.

Gastroprotective action of Cochinchina momordica seed extract is mediated by activation of CGRP and inhibition of cPLA(2)/5-LOX pathway.

Cochinchina momordica seed extract (SKMS10), which is composed of the major compounds momordica saponins, has been evaluated for its gastroprotective effects in rat models of acute gastric mucosal damage. Ethanol and water immersion restraint stress (WRS) induced gastric damage, including hemorrhages and edema, was significantly attenuated by pretreatment with SK-MS10. In addition, SK-MS10 reduced increases of mucosal myeloperoxidase (MPO), IL-1ß, and TNFα levels and the expression of cPLA(2), and 5-LOX induced by ethanol or WRS. SK-MS10 also increased hexosamine, adherent mucus, and the expression of MUC5AC. Furthermore, SK-MS10 enhanced the mucosal expression of the CGRP gene and its serum levels.N(G)-methyl L-arginine (L-NMMA) or capsaicin desensitization reversed the SK-MS10-induced gastroprotection effect. These results suggest that SK-MS10 is a gastroprotective agent against acute gastric mucosal damage by suppressing proinflammatory cytokines, downregulating cPLA(2), 5-LOX, and increasing the synthesis of mucus. Furthermore, CGRP-NO pathway was found to play an important role in these gastroprotective effects of SK-MS10.

Combined Assessment of Preschool Childrens' Exposure to Substances in Household Products.

Understanding how indoor-air contaminants affect human health is of critical importance in our developed society. We assessed the combined exposure by inhalation of preschool children and children to household products. A total of 1175 families with 72 infants, 158 toddlers, 230 children, and 239 youths were surveyed to determine the combined respiratory exposure concentrations and amounts associated with 21 substances in eight household product groups. We determined the mean concentrations of these substances in each product, and derived reference toxicity values based on the information gathered in order to identify respiratory health risks. On average, cleaners were used at a rate of 1.0 × 10³ g/month, while coating agents and other substances were used at 43 g/month. The combined inhalation exposure concentrations of methanol to infants and toddlers were 5.1 and 4.2 mg/m³ per month, respectively, with values of 2.1 and 1.7 mg/m³ for isopropanol, respectively. Risks to preschool children and children should be assessed on the basis of the toxicity values of combined exposed hazardous substances, as well as their combined concentrations and amounts. This exposure assessment approach can be used to establish improved guidelines for products that may pose inhalation hazards to preschool children and children.

Inhalation exposure factors from the use of household products in South Korea.

Exposure assessment, a fundamental element of the risk assessment process, is the estimation of what consumers may be exposed to by using household products. Reliable exposure factors were investigated to understand the pattern of household products usage. Six household product categories were selected and divided by application types. Two surveys were carried out and 6397 participants completed the web-based questionnaires, and laboratory evaluations were also conducted to measure the actual level of exposure (g/use). We focused more on inhalation exposure from products (and/or their application types) that affect indoor air such as diffusible types. To estimate actual exposure amounts, the time spent to apply the products was investigated from the beginning to end of the product use. For spraying type products, the consumer could be exposed to the maximum amount of used product while using the triggering action and pressing the button on the aerosol spray product, and during cleaning, adhesion, and coating target, consumer could be exposed continuously. For diffuser type products, exposure duration was the time for which consumers were exposed to the diffused product. The exposure amount for trigger and aerosol spray type products were measured using the time taken to trigger or spray the product and the mass generated from the same. This study provides valuable information on the individual exposure factors that may be useful to conduct accurate exposure assessments and to manage household products.

Potential Health Risks of Chemicals in Car Colorant Products.

Public concern regarding the use of products with chemicals has increased in Korea, following reports indicating that hazardous chemicals in products, such as disinfectants, can cause fatal lung disease. Despite the widespread use of car colorant products, little is known regarding their potential health risks. The purpose of this study was to determine the potential health risks of substances that exist in car colorant products. Thirteen car colorant products were purchased from the Korean market and 15 commonly used chemicals were analyzed. Exposure and risk assessments were conducted in two assessment stages (screening and refined). The analysis showed that all of the examined products contained toluene, ethylbenzene, and xylene. The maximum concentration of toluene was 52.5%, with a median concentration of 10.8%. Tier 1 (screening) assessment showed that four chemicals (toluene, ethylbenzene, xylene, and 2-butoxyethanol) may pose health risks, but tier 2 (refined) assessment showed that these chemicals do not pose any risk. However, these chemicals were present in all of the examined products, and government regulations did not control their concentrations in these products. Therefore, we suggest that levels of toluene, ethylbenzene, and xylene in car colorant products should be regulated to protect public health.

Determining Exposure Factors of Anti-Fogging, Dye, Disinfectant, Repellent, and Preservative Products in Korea.

Reliable exposure factors are essential to determine health risks posed by chemicals in consumer products. We analyzed five risk-concerned product categories (anti-fogging, dye, disinfectant, repellent, and preservative products) for 13 products (three car anti-fogging products, a lens anti-fogging product, two car dye products, two drain disinfectants, an air conditioner disinfectant, a chlorine-based disinfectant, a fabric repellent, an insect repellent for food, and a wood preservative) considered to be of high risk in order to determine exposure factors via web surveys and estimation of amount of product. Among the 3000 participants (1482 (49%) men) aged ≥19 years, drain disinfectants were used most frequently (38.2%); the rate of usage of the other products ranged between 1.1-24.0%. The usage rates for the consumer products differed by sex, age, income, and education. Some consumer products such as car and lens anti-fogging products, chlorine-based disinfectants, fabric repellents, and drain disinfectants were regularly used more than once a month, while car dye products, air conditioner disinfectants, insect repellents for food, and wood preservatives were not regularly used owing to the specific product purposes and seasonal needs. Our results could be used for managing or controlling chemical substances in consumer products and conducting accurate exposure assessments.

Health Risk Assessment on Hazardous Ingredients in Household Deodorizing Products.

The inhalation of a water aerosol from a humidifier containing disinfectants has led to serious lung injuries in Korea. To promote the safe use of products, the Korean government enacted regulations on the chemicals in various consumer products that could have adverse health effects. Given the concern over the potential health risks associated with the hazardous ingredients in deodorizing consumer products, 17 ingredients were analyzed and assessed according to their health risk on 3 groups by the application type in 47 deodorizing products. The risk assessment study followed a stepwise procedure (e.g., collecting toxicological information, hazard identification/exposure assessment, and screening and detailed assessment for inhalation and dermal routes). The worst-case scenario and maximum concentration determined by the product purpose and application type were used as the screening assessment. In a detailed assessment, the 75th exposure factor values were used to estimate the assumed reasonable exposure to ingredients. The exposed concentrations of seven ingredients were calculated. Due to limitation of toxicity information, butylated hydroxyl toluene for a consumer’s exposure via the dermal route only was conducted for a detailed assessment. This study showed that the assessed ingredients have no health risks at their maximum concentrations in deodorizing products. This approach can be used to establish guidelines for ingredients that may pose inhalation and dermal hazards.

Health risk assessment of dermal and inhalation exposure to deodorants in Korea.

In Korea, humidifiers that include biocidal ingredients have caused serious lung injuries and deaths. After these incidents, public concern regarding the use of chemicals in products (i.e., chemical phobia) increased. Frequent health risk assessments and stringent management of consumer products are, therefore, of paramount importance to reduce these serious occurrences. In this study, the irritative and respiratory health effects of deodorants were assessed in relation to dermal and inhalation exposure. In total, 64 deodorants were divided into 5 groups by application type, and health risk assessments were conducted on each group. In total, 26 fragrance ingredients and 27 biocidal ingredients were analyzed and assessed according to their risk to human health. Exposure assessment was performed in two steps. In the tiered 1 assessment (screening), the 95th exposure factor values were used to estimate exposure to assume the worst-case scenario. The maximum concentration in the deodorants was used without considering the application type. In the tiered 2 assessment (detail assessment), the 75th exposure factor values were used to estimate the assumed reasonable exposure to ingredients. In these assessments, the maximum concentration used in the exposure models was determined by the product purpose and application type. The values input into the exposure algorithms were developed via the exposure route. Of the selected fragrance and biocidal active ingredients, 18 fragrance and 13 biocidal ingredients were detected in the deodorants that were assessed. From the results of the tiered 1 assessment, it was necessary for tiered 2 risk assessments to be conducted for 6 ingredients for the inhalation route, and 13 ingredients for the dermal route. The inhalation margin of exposure of ingredients in deodorants of gel/trigger/spray types for home/car and fabric/air usage was above the target margin of exposure. The health risk of 6 evaluated ingredients was relatively low for the inhalation route of exposure. This study showed that the assessed ingredients have no health risks at their maximum concentrations in deodorants. The approach discussed in this study should be used to establish improved guidelines for specific ingredients in consumer products, and for setting limits for newly developed raw materials that may pose dermal and inhalation hazard.

Impact of Long-Term Proton Pump Inhibitor Therapy on Gut Microbiota in F344 Rats: Pilot Study.

BACKGROUND/AIMS: To evaluate changes in gut microbiota composition following long-term proton pump inhibitor (PPI) treatment. METHODS: Twenty-four-week-old F344 rats were fed diets with (n=6) or without (n=5) lansoprazole for 50 weeks. Profiles of luminal microbiota in the terminal ileum were then analyzed. Pyrosequencing of the 16S rRNA gene was performed using an FLX genome sequencer (454 Life Sciences/Roche). RESULTS: Rats treated with lansoprazole showed significantly reduced body weights compared to controls (lansoprazole-treated rats and controls, 322.3±15.3 g vs 403.2±5.2 g, respectively, p<0.001). However, stool frequencies and consistencies did not differ between the two groups. The composition of the gut microbiota in lansoprazole-treated rats was quite different from that of the controls. In the controls, the microbiota profiles obtained from the terminal ileum showed a predominance of Proteobacteria (93.9%) due to the abundance of Escherichia and Pasteurella genera. Conversely, lansoprazole-treated rats showed an elevated population of Firmicutes (66.9%), which was attributed to an increased ratio of Clostridium g4 to Lactobacillus genera. CONCLUSIONS: This preliminary study suggests that long-term administration of PPI may cause weight loss and changes to the microbiota in the terminal ileum.

SKI306X, an oriental herbal mixture, suppresses gastric leukotriene B4 synthesis without causing mucosal injury and the diclofenac-induced gastric lesions.

SKI306X compound is a herbal mixture. This plant was in oriental medicine and was clinically approved for the treatment of osteoarthritis (OA) in Korea. SKI306X was previously found to have anti-inflammatory, analgesic and cartilage protective effects in several experimental models. In this study, SKI306X was investigated for its gastro-sparing effects on the gastric mucosa comparing with those of diclofenac, a conventional NSAID, and celecoxib, a cyclooxygenase-2 (COX-2) specific inhibitor. To investigate acute gastric damaging properties of SKI306X, the stomach of the animals was histologically and immuno-histochemically examined after single or repeated administration, and SKI306X demonstrated excellent gastric tolerability. SKI306X did not cause significant gastric irritation, erosion, or ulceration up to the orally administered dose of 2 g/kg and the intraperitoneal (i.p.) dose of 125 mg/kg. In contrast, diclofenac caused mucosal erosion, ulceration and bleeding at clinically effective doses. To determine the mode of gastro-sparing action, eicosanoid synthesis was examined in gastric mucosa and blood. SKI306X significantly decreased gastric and blood leukotriene B(4) (LTB(4)) production. However, SKI306X showed either no effect or a slight increase in levels of prostaglandin E(2) (PGE(2)). In addition, gastro-protective effects of SKI306X were exhibited by suppressing diclofenac-induced erosion and ulceration of gastric mucosa in a rat model and the possible mechanism of these effects were investigated. These studies demonstrated that SKI306X did not produce any significant damage up to dose of 2 g/kg and was effective in significantly protecting the damage associated to diclofenac-induced gastric ulcerations. SKI306X could spare the gastric mucosa through significantly suppressing gastric leukotriene (LT) synthesis.

Refolding of the catalytic and hinge domains of human MT1-mMP expressed in Escherichia coli and its characterization.

The catalytic and hinge domain (Tyr112-Ile318) of the human membrane type-1 matrix metalloproteinase (MT1-MMP; MMP-14), containing hexa-histidines at the C-terminus (chMT1-MMP), was overexpressed in Escherichia coli. The expressed polypeptide was almost exclusively found in the inclusion body, and then purified by a single Ni2+-NTA agarose column chromatography after solubilization with 6 M urea. During refolding, the 26.9 kDa chMT1-MMP was processed to a 24.3 kDa intermediate form and then to a 22.2 kDa mature form. By Western blot analysis and mass spectrometry combined with N-terminal sequencing, the intermediate form was identified as a mixture of the Tyr112-Thr299 with a translation-initiating methionine and Ile114-Thr299, and that the mature form corresponds to Ile114-Pro290. These results demonstrate that the mature form was generated by successive autoproteolysis of the N- and C-terminal sites between Thr299-Thr300, Ala113-Ile114, and Pro290-Thr291 during refolding. Catalytic activity of the mature chMT1-MMP was demonstrated by a peptide cleavage assay. In addition, it has gelatinolytic activity and is able to activate proMMP-2 to the mature MMP-2. These results indicate that the refolded chMT1-MMP retains characteristics of MT1-MMP.

The Effect of Cochinchina momordica Seed Extract on Gastric Acid Secretion and Morphologic Change in Aged Rat Stomach.

BACKGROUND/AIMS: Cochinchina momordica seed extract (SK-MS10) has a gastric protective effect. We aimed to assess the effect of SK-MS10 on gastric acid secretion with morphologic changes in the aged rat. METHODS: Acid secretions were evaluated in the male F344 rats of four different ages (6-, 31-, 74-week, and 2-year). The 31-week-old rats were divided to three groups and continuously administered chow containing vehicle, SK-MS10 and lansoprazole, respectively. At the age of 74 weeks and 2 years, basal and stimulated acid was measured and the expression of mRNA and protein of H(+)-K(+)-ATPase were determined. The area of connective tissue of lamina propria was measured. RESULTS: Basal and stimulated gastric acid significantly decreased and connective tissue of lamina propria increased with age. The expression of mRNA and protein of H(+)-K(+)-ATPase significantly decreased with age. However, 74-week-old rats in the SK-MS10 group had higher stimulated gastric acid secretion than those in the vehicle and lansoprazole groups. In 2-year-old rats of SK-MS10 group, there was no increase of connective tissue. CONCLUSIONS: As SK-MS10 kept the capacity of acid secretion as well as connective tissue area to comparable to young rats, it might valuable to perform further research regarding mechanism of SK-MS10 as an antiaging agent in the stomach.

Comparison of Indomethacin, Diclofenac and Aspirin-Induced Gastric Damage according to Age in Rats.

BACKGROUND/AIMS: Aging gastric mucosa is known to have decreased mucosal defenses and increased susceptibility to injury by nonsteroidal anti-inflammatory drugs. Depending on the type of nonsteroidal anti-inflammatory drug (NSAID), the underlying mechanisms and the extent of damage to the stomach or intestine may differ. This study was performed to evaluate the acute gastric damage caused by different doses of indomethacin, diclofenac and aspirin in rats of various ages. METHODS: For the acute models, indomethacin (10, 20 or 40 mg/kg), diclofenac (40 or 80 mg/kg) or aspirin (100 mg/kg) was given to 7- and 25-week-old and 1-year-old Sprague-Dawley rats by intragastric gavage. The gross ulcer index, damage area as assessed by imaging, histological index, myeloperoxidase (MPO) activity, and cytosolic phospholipase A(2) (cPLA(2)) levels were measured after 24 hours. RESULTS: The gross ulcer index and damage area increased with age in the presence of three NSAIDs (p<0.05). The increases in MPO levels induced by diclofenac and aspirin were significantly higher in 1-year-old than 7-week-old rats (p<0.05). cPLA(2) expression induced by indomethacin (10 and 40 mg/kg) was greater in the 1-year-old rats, compared with 7-week-old rats (p<0.05). CONCLUSIONS: NSAID-induced acute gastric damage increased in a dose- and age-dependent manner.