Anti-inflammatory, antipyretic efficacy and safety of inhaled Houttuynia cordata thunb. essential oil formulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb. (H. cordata) is a well-known folk traditional Chinese medicine that is renowned for its use in the management of inflammatory respiratory diseases and pneumonia. Its essential oils have demonstrated their anti-inflammatory efficacy in vitro, however, their in vivo biological effects via inhalation have not been elucidated. AIM OF THE STUDY: This study aims to evaluate the anti-inflammation and toxicology of H. cordata essential oil-containing formulation, H16 aerosol in vivo. MATERIALS AND METHODS: A laser diffraction particle size analyser and a Next Generation Impactor were used to measure the mass median aerodynamic diameter (MMAD) of the H16 aerosol. The anti-inflammatory and antipyretic effects of the H16 aerosol were evaluated in the xylene-evoked ear oedema and Brewer's yeast-induced fever models, respectively. The biological safety of the H16 aerosol was evaluated by acute toxicity and local toxicity tests in animal models. RESULTS: Our data showed that the MMAD of the bioactive aerosol was 3-5 µm, which implied tracheal and pharyngeal deposits. Significant anti-inflammatory and antipyretic effects were also observed in the animal models treated with H16 aerosol. The maximum tolerable dose of H16 in rats was >2.5 mL/kg. Irritation was not found on respiratory tract mucosa in the local toxicity test. CONCLUSIONS: Taken together, the present study suggested that H16 could be delivered in the form of aerosol and possessed its antipyretic and anti-inflammatory effects. This study provides a new perspective for the development of a new herbal aerosol therapy and herbal modernization.

Chemical, biological and protein-receptor binding profiling of Bauhinia scandens L. stems provide new insights into the management of pain, inflammation, pyrexia and thrombosis.

Bauhinia scandens L. (Family, Fabaceae) is a medicinal plant used for conventional and societal medication in Ayurveda. The present study has been conducted to screen the chemical, pharmacological and biochemical potentiality of the methanol extracts of B. scandens stems (MEBS) along with its related fractions including carbon tetrachloride (CTBS), di-chloromethane (DMBS) and n-butanol (BTBS). UPLC-QTOF-MS has been implemented to analyze the chemical compounds of the methanol extracts of Bauhinia scandens stems. Additionally, antinociceptive and anti-inflammatory effects were performed by following the acetic acid-induced writhing test and formalin-mediated paw licking test in the mice model. The antipyretic investigation was performed by Brewer Yeast induced pyrexia method. The clot lysis method was implemented to screen the thrombolytic activity in human serum. Besides, the in silico study was performed for the five selected chemical compounds of Bauhinia scandens, found by UPLC-QTOF-MS By using Discover Studio 2020, UCSF Chimera, PyRx autodock vina and online tools. The MEBS and its fractions exhibited remarkable inhibition in dose dependant manner in the antinociceptive and antiinflammatory investigations. The antipyretic results of MEBS and DMBS were close to the standard drug indomethacin. Investigation of the thrombolytic effect of MEBS, CTBS, DMBS, and BTBS revealed notable clot-lytic potentials. Besides, the phenolic compounds of the plant extracts revealed strong binding affinity to the COX-1, COX-2, mPGES-1 and plasminogen activator enzymes. To recapitulate, based on the research work, Bauhinia scandens L. stem and its phytochemicals can be considered as prospective wellsprings for novel drug development and discovery by future researchers.

Drug-induced liver injury in Australia, 2009-2020: the increasing proportion of non-paracetamol cases linked with herbal and dietary supplements.

OBJECTIVE: To compare the characteristics and outcomes of drug-induced liver injury (DILI) caused by paracetamol and non-paracetamol medications, particularly herbal and dietary supplements. DESIGN: Retrospective electronic medical record data analysis. SETTING, PARTICIPANTS: Adults admitted with DILI to the Gastroenterology and Liver Centre at the Royal Prince Alfred Hospital, Sydney (a quaternary referral liver transplantation centre), 2009-2020. MAIN OUTCOME MEASURES: 90-day transplant-free survival; drugs implicated as causal agents in DILI. RESULTS: A total of 115 patients with paracetamol-related DILI and 69 with non-paracetamol DILI were admitted to our centre. The most frequently implicated non-paracetamol medications were antibiotics (19, 28%), herbal and dietary supplements (15, 22%), anti-tuberculosis medications (six, 9%), and anti-cancer medications (five, 7%). The number of non-paracetamol DILI admissions was similar across the study period, but the proportion linked with herbal and dietary supplements increased from 2 of 13 (15%) during 2009-11 to 9 of 19 (47%) during 2018-20 (linear trend: P = 0.011). Despite higher median baseline model for end-stage liver disease (MELD) scores, 90-day transplant-free survival for patients with paracetamol-related DILI was higher than for patients with non-paracetamol DILI (86%; 95% CI, 79-93% v 71%; 95% CI, 60-82%) and herbal and dietary supplement-related cases (59%; 95% CI, 34-85%). MELD score was an independent predictor of poorer 90-day transplant-free survival in both paracetamol-related (per point increase: adjusted hazard ratio [aHR], 1.19; 95% CI, 1.09-3.74) and non-paracetamol DILI (aHR, 1.24; 95% CI, 1.14-1.36). CONCLUSION: In our single centre study, the proportion of cases of people hospitalised with DILI linked with herbal and dietary supplements has increased since 2009. Ninety-day transplant-free survival for patients with non-paracetamol DILI, especially those with supplement-related DILI, is poorer than for those with paracetamol-related DILI.

Pharmacological evaluation of analgesic, anti-inflammatory and antipyretic activities of ethanolic extract of Indigofera argentea Burm. f.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigofera argentea Burm. f.; commonly known as neel, jantari, hathio; is traditionally used for the treatment of headache, fever, inflammation and body pain. Local communities also used this plant for the treatment of malaria, jaundice, vertigo and gastric disorders. AIM OF THE STUDY: This study is aimed to evaluate the toxicity and possible analgesic, anti-inflammatory and antipyretic activities of the ethanolic crude extract of Indigofera argentea (IaCr) to support its use in folk medicine and to screen the phytochemical constituents and antioxidant activity. MATERIALS AND METHODS: Aqueous ethanolic (30:70) extract of whole plant of Indigofera argentea (IaCr) was prepared and phytochemical study was performed by preliminary methods followed by HPLC and DPPH method. In vivo experiments were performed in Wistar albino rats including hot plate, tail immersion, formalin and capsaicin-induced pain tests in rats and acetic acid-induced writhing test in mice. Anti-inflammatory activity was assessed by using in vitro human red blood cell (HRBC) membrane stabilization and carrageenan-induced rat paw edema test, while antipyretic activity was evaluated by Brewer's yeast-induced pyrexia test. RESULTS: The crude extract of Indigofera argentea confirmed the presence of flavonoids, glycosides, alkaloids, saponins and tannins as soluble ethanolic constituents in preliminary study. The maximum quantity of gallic acid equivalent (GAE) phenolics, and quercetin equivalent (QE) flavonoid content found was 81 ± 2 mg GAE/g and 56 ± 1.4 mg QE/g of extract respectively. Quantification based on HPLC exposed the presence of phenols and flavonoids, quercetin, gallic acid, caffeic acid, chlorogenic acid, benzoic acid, ferulic acid and coumaric acid. In vivo experiments revealed significant P < 0.05) dose-dependent inhibition in hot plate, tail immersion and capsaicin-induced pain test. IaCr showed significant inhibition of pain latency against both phases in formalin test and considerably decreased the number of writhes caused by acetic acid at the doses of 30, 100 and 300 mg/kg. In the in vitro anti-inflammatory (HRBC) assay, IaCr showed good membrane stability with maximum percentage hemolysis inhibition of 49.29% while in carrageenan-induced paw edema test in rats the IaCr showed significant anti-inflammatory action in a dose-dependent fashion. Statistical significant reduction in rectal temperature was observed at the doses of 100 and 300 mg/kg in yeast-induced pyrexia test in rats. CONCLUSION: The results of the experimental studies proved the analgesic, anti-inflammatory and antipyretic activities of Indigofera argentea and supported the traditional use of this plant.

A computational model for hepatotoxicity by coupling drug transport and acetaminophen metabolism equations.

The spatial distributions of cytochrome P450 (CYP450) and glutathione (GSH) in liver lobules determine the heterogeneous hepatotoxicity of acetaminophen (APAP). Their interplay in conjunction with blood flow is not well understood. In this paper, we integrate a cellular APAP metabolism model with a sinusoidal blood flow to simulate the temporal-spatial patterns of APAP-induced hepatotoxicity. The heterogeneous distribution of CYP450 and GSH is modeled by linearly varying their reaction rates along the portal triad to the central vein axis of a sinusoid. We found that the spatial distribution of GSH, glutathione S-transferases (GSTs), and CYP450 all contributes to the high acetaminophen protein adduct formation at zone 3 of the lobules. The reversed spatial gradients of CYP450 and GSH cause quick depletion of GSH, which is further accelerated by the distribution of GST. The hepatic flow congestion and hyperperfusion however do not seem to play a significant role in the zonal hepatotoxicity. The simulation results may be useful for understanding the APAP-induced hepatotoxicity and associated pharmaceutical treatment.

Lipopolysaccharide protects against acetaminophen-induced hepatotoxicity by reducing oxidative stress via the TNF-α/TNFR1 pathway.

Robust evidence suggested that gut-derived lipopolysaccharide (LPS) plays a significant role in various liver injury diseases; however, the role of gut-derived LPS in acetaminophen (APAP) overdose-induced acute liver injury remains unclear. The present study aimed to investigate the effect of gut-derived LPS on APAP-induced liver injury. Our results revealed that reduction of gut-derived LPS using multiple antibiotics could significantly exacerbate APAP-induced liver injury and increase mortality in mice. By contrast, pretreatment with exogenous LPS could reverse APAP-induced liver hepatotoxicity in mice and rats. We observed that TNF-α secretion in the liver was significantly increased after LPS pretreatment. In addition, depletion of TNF-α or TNFR1 inhibited the protective effects of LPS against APAP-induced hepatotoxicity, which indicated that the TNF-α/TNFR1 pathway was required to protect against APAP-induced liver injury. Mechanistically, LPS reduces oxidative stress by upregulating the expression of hepatic GSH, reducing MDA levels in liver tissues, and upregulating the expression of several antioxidant genes after APAP injection. However, the production of hepatic GSH was not enhanced in the liver tissues of rats lacking TNF-α or TNFR1 and MDA levels were not reduced after LPS and APAP co-treatment. The above results suggested LPS alleviated APAP-induced oxidative stress via the TNF-α/TNFR1 pathway.

Synthesis and Biological Evaluation of Polyfluoroalkylated Antipyrines and their Isomeric O-Methylpyrazoles.

BACKGROUND: Formally belonging to the non-steroidal anti-inflammatory drug class pyrazolones have long been used in medical practices. OBJECTIVE: Our goal is to synthesize N-methylated 1-aryl-3-polyfluoroalkylpyrazolones as fluorinated analogs of antipyrine, their isomeric O-methylated derivatives resembling celecoxib structure and evaluate biological activities of obtained compounds. METHODS: In vitro (permeability) and in vivo (anti-inflammatory and analgesic activities, acute toxicity, hyperalgesia, antipyretic activity, "open field" test) experiments. To suggest the mechanism of biological activity, molecular docking of the synthesized compounds was carried out into the tyrosine site of COX-1/2. RESULTS: We developed the convenient methods for regioselective methylation of 1-aryl-3- polyfluoroalkylpyrazol-5-ols leading to the synthesis N-methylpyrazolones and O-methylpyrazoles as antipyrine and celecoxib analogs respectively. For the first time, the biological properties of new derivatives were investigated in vitro and in vivo. CONCLUSION: The trifluoromethyl antipyrine represents a valuable starting point in design of the lead series for discovery new antipyretic analgesics with anti-inflammatory properties.

Synthesis, hepatotoxic evaluation and antipyretic activity of nitrate ester analogs of the acetaminophen derivative SCP-1.

A series of nitrate ester analogues of the acetaminophen derivative SCP-1 were prepared by triflic acid catalyzed O-acylation of SCP-1 with chloroalkanoyl chlorides followed by nitration with silver nitrate. The chloroesters and corresponding nitrate esters were obtained in high yields. Preliminary hepatotoxicity studies revealed nitrate esters 5b (MD-38) and 5c (MD-39) to be well tolerated by human hepatocytes and had little effect on the three cytochrome P450 enzymes tested (CYP3A4, CYP2E1 and CYP2D6). In addition, the nitrate ester 5c (MD-39) exhibited antipyretic activity similar to acetaminophen.

A 13-week subchronic toxicity study of acetaminophen using an obese rat model.

Although obesity is increasing worldwide, experimental studies examining the possible association between obesity and susceptibility to chemical toxicity are limited. In the present study, we performed a 13-week toxicity study for acetaminophen (APAP), a well-known drug that exhibits hepatotoxicity as an adverse effect, using an obese rat model to investigate the differences in susceptibility between obese and normal individuals. Male F344 and obese Zucker (lean and fatty) rats were administered 0, 80, 253, 800, 2,530, or 8,000 ppm APAP in the diet for 13 weeks. No significant toxicity related to APAP treatment was observed in terms of clinical signs and hematology in all three strains. Body weight gain in F344 and lean rats was significantly decreased by 8,000 ppm APAP treatment. Significant increases in serum total cholesterol level and relative liver weights were detected in F344 rats in the highest dose group. On histopathological assessment, centrilobular hepatocellular hypertrophy was observed in the 8,000 ppm groups of F344 and lean rats, whereas no histopathological changes were induced by APAP in fatty rats. The no-observed-adverse-effect levels (NOAELs) of APAP were evaluated to be 2,530 ppm in F344 and lean rats (142.1 and 152.8 mg/kg bw/day, respectively) and more than 8,000 ppm in fatty rats (> 539.9 mg/kg bw/day). These results suggested that obese Zucker rats may be less susceptible to APAP-dependent toxicity in the liver than their lean counterparts.

Lophirones B and C halt acetaminophen hepatotoxicity by upregulating redox transcription factor Nrf-2 through Akt, PI3K, and PKC pathways.

We investigated the mechanism of lophirones B- and C-mediated protection against acetaminophen hepatotoxicity. Mice were pretreated with 20 mg/kg body weight lophirones B and C for 7 days and challenged with acetaminophen on day 7. Acetaminophen raised nuclear factor-κB (NF-κB) in the liver of mice but lowered protein kinase B (Akt). Although, acetaminophen produced no significant alteration on nuclear erythroid related factor-2 (Nrf-2), phosphoinositide 3-kinase (PI3K) and protein kinase C (PKC), lophirones B and C raised the level of these proteins and Akt. The acetaminophen-mediated increase in NF-κB was significantly reversed by lophirones B and C. Lophirones B and C prevented acetaminophen-mediated alterations in serum biomarkers of hepatic injury. Similarly, lophirones B and C lowered the biomarkers of oxidative stress in the liver of acetaminophen-treated mice. It can be inferred from this study that lophirones B and C prevent acetaminophen-induced liver injury by enhancing Nrf-2 through Akt, PI3K, and PKC pathways.

Effect of early natal supplementation of paracetamol on attenuation of exotoxin/endotoxin induced pyrexia and precipitation of autistic like features in albino rats.

The present study was aimed to test the hypothesis that paracetamol (PCM) can precipitate autistic like features when used to counteract vaccine-induced fever using experimental rat pups. The pups were treated with measles mumps rubella (MMR) vaccine, diphtheria tetanus and pertussis (DPT) vaccines and lipopolysaccharide (LPS) with subsequent PCM treatment. The pups were evaluated for postnatal growth (weight gain, eye opening) and behavior alterations (swimming performance, olfactory discrimination, negative geotaxis, nociception, and locomotor activity) by performing battery of neurobehavioral test. Significant correlation was observed between social behavioral domains (nociception, anxiety and motor coordination) and pro-inflammatory load in the pups when treated with MMR/LPS along with PCM. A significant change in pro and anti-inflammatory (IL-4, IL-6, IL-10) markers were observed in rats treated with PCM, MMR, LPS, DPS alone or in combination with MMR, LPS and DPT (5128.6 ± 0.000, 15,488 ± 0.000***, 9661.1 ± 157.29***a, 15,312 ± 249.29***, 10,471 ± 0.00***a, 16,789 ± 273.34*** and 12,882 ± 0.00***a). Pups were also scrutinized for the markers of oxidative stress, inflammation and histopathologically. All the treatment groups showed significant alteration in the behavioral changes, oxidative markers (TBARS-in control-4.33 ± 0.02, PCM-9.42 ± 0.18***, MMR-5.27 ± 0.15***, MMR + PCM-8.57 ± 0.18*** a, LPS-6.84 ± 0.10***, LPS + PCM-4.51 ± 0.30***a, DPT-5.68 ± 0.12***, DPT + PCM-7.26 ± 0.18***a) and inflammatory markers without following any specific treatment. These observation could be accorded to variable phenotypes of autistic spectrum disorders (ASDs).

Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and protective effects of various compounds in vivo and in vitro.

Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress. This review updates the research conducted over the past decades into the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and oxidative stress as a result of APAP treatments, and ultimately their correlation with the toxicity and metabolism of APAP. The metabolism of APAP involves various CYP450 enzymes, through which oxidative stress might occur, and such metabolic factors are reviewed within. The therapeutics of a variety of compounds against APAP-induced organ damage based on their anti-oxidative effects is also discussed, in order to further understand the role of oxidative stress in APAP-induced toxicity. This review will throw new light on the critical roles of oxidative stress in APAP-induced toxicity, as well as on the contradictions and blind spots that still exist in the understanding of APAP toxicity, the cellular effects in terms of organ injury and cell signaling pathways, and finally strategies to help remedy such against oxidative damage.

Antipyretic potential of herbal coded formulation (Pyrexol).

The antipyretic effect of the aqueous extract of herbal coded formulation containing equal amount of Salix alba, Emblica officinalis, Glycyrrhiza glabra, Adhatoda vasica, Viola odorata, Thea sinensis, Veleriana officinalis, Foeniculum vulgare, Sisymbrium irrio and Achillea millefolium was investigated using the yeast induced pyrexia model in rabbits. Paracetamol was used as a control group. Rectal temperatures of all rabbits were recorded immediately before the administration of the extract or paracetamol and again at 1 hour, after this, temperature was noted at 1 hrs interval for 5 hrs using digital thermometer. At 240mg/kg dose the extract showed significant reduction in yeast-induced elevated temperature as compared with that of standard drug paracetamol (150mg/kg). It is concluded that herbal coded medicine at a dose of 240mg/kg has marked antipyretic activity in animal models and this strongly supports the ethno pharmacological uses of medicinal plants of this formulation.

New Phenylpropanoid and Coumarin Glycosides from the Stems of Hydrangea paniculata Sieb.

A new phenylpropanoid glycoside (1), and two new coumarin glycosides (2, 3), together with two known compounds (4, 5), have been isolated from the stems of Hydrangea paniculata Sieb. Their structures have been determined by spectroscopic and chemical methods. Furthermore, compound 1 (50 µM) exhibited significant hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage in vitro assays.

An evaluation of the anti-inflammatory, antipyretic and analgesic effects of hydroethanol leaf extract of Albizia zygia in animal models.

CONTEXT: The leaves of Albizia zygia (DC.) J.F. Macbr. (Leguminosae-Mimosoideae) are used in Ghanaian traditional medicine for the treatment of pain, inflammatory disorders and fever (including malaria). OBJECTIVES: The present study evaluated the anti-inflammatory, antipyretic and analgesic effects of the hydroethanol leaf extract of Albizia zygia (AZE) in animal models. MATERIALS AND METHODS: The anti-inflammatory and antipyretic effects of AZE were examined in the carrageenan-induced foot oedema model and the baker's yeast-induced pyrexia test respectively. The analgesic effect and possible mechanisms of action were also assessed in the formalin test. RESULTS: AZE (30-300 mg/kg, p.o.), either preemptively or curatively, significantly inhibited carrageenan-induced foot edema in 7-day-old chicks (ED50 values; preemptive: 232.9 ± 53.33 mg/kg; curative: 539.2 ± 138.28 mg/kg). Similarly, the NSAID diclofenac (10-100 mg/kg, i.p.) significantly reduced the oedema in both preemptive (ED50: 21.16 ± 4.07 mg/kg) and curative (ED50: 44.28 ± 5.75 mg/kg) treatments. The extract (30-300 mg/kg, p.o.) as well as paracetamol (150 mg/kg, p.o.) also showed significant antipyretic activity in the baker's yeast-induced pyrexia test (ED50 of AZE: 282.5 ± 96.55 mg/kg). AZE and morphine (1-10 mg/kg, i.p.; positive control), exhibited significant analgesic activity in the formalin test. The analgesic effect was partly or wholly reversed by the systemic administration of naloxone, theophylline and atropine. CONCLUSION: The results suggest that AZE possesses anti-inflammatory, antipyretic and analgesic properties, which justifies its traditional use. Also, the results show the involvement of the opioidergic, adenosinergic and the muscarinic cholinergic pathways in the analgesic effects of AZE.

Altered protein S-glutathionylation identifies a potential mechanism of resistance to acetaminophen-induced hepatotoxicity.

Acetaminophen (APAP) is the most commonly used over-the-counter analgesic. However, hepatotoxicity induced by APAP is a major clinical issue, and the factors that define sensitivity to APAP remain unclear. We have previously demonstrated that mice nulled for glutathione S-transferase Pi (GSTP) are resistant to APAP-induced hepatotoxicity. This study aims to exploit this difference to delineate pathways of importance in APAP toxicity. We used mice nulled for GSTP and heme oxygenase-1 oxidative stress reporter mice, together with a novel nanoflow liquid chromatography-tandem mass spectrometry methodology to investigate the role of oxidative stress, cell signaling, and protein S-glutathionylation in APAP hepatotoxicity. We provide evidence that the sensitivity difference between wild-type and Gstp1/2(-/-) mice is unrelated to the ability of APAP to induce oxidative stress, despite observing significant increases in c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation in wild-type mice. The major difference in response to APAP was in the levels of protein S-glutathionylation: Gstp1/2(-/-) mice exhibited a significant increase in the number of S-glutathionylated proteins compared with wild-type animals. Remarkably, these S-glutathionylated proteins are involved in oxidative phosphorylation, respiratory complexes, drug metabolism, and mitochondrial apoptosis. Furthermore, we found that S-glutathionylation of the rate-limiting glutathione-synthesizing enzyme, glutamate cysteine ligase, was markedly increased in Gstp1/2(-/-) mice in response to APAP. The data demonstrate that S-glutathionylation provides an adaptive response to APAP and, as a consequence, suggest that this is an important determinant in APAP hepatotoxicity. This work identifies potential novel avenues associated with cell survival for the treatment of chemical-induced hepatotoxicity.

Ninety-Day Subchronic Oral Toxicity Study of Senecio scandens Extract in Rats.

The present study assessed the safety/toxicity of Senecio scandens, a well-known Chinese herb that is used as an anti-inflammatory, antibiosis, and antipyretic drug. A 90-d subchronic oral toxicity study of S. scandens was performed in Wistar rats. The extract of S. scandens was administered orally to male and female rats at a single dose of 225, 450, and 900 mg/kg/d. There was no obvious toxicity. Certain changes in hematology and coagulation parameters (red cell distribution width (RDW), platelet count (PLT), monocyte percentage (Mo%), activated partial thromboplastin time (APTT), prothrombin time (PT)) were observed in some administration groups. In regards to the blood biochemical parameters, the levels of creatinine (CRN), potassium, and chloride were increased in a number of the treated rats. There were no significant changes in other hematology, coagulation, or biochemical parameters in rats orally administered S. scandens. S. scandens has a slight effect on rat coagulation and metabolism systems. The herb was safe at all doses tested, but caution should be taken when administering S. scandens at higher doses.

Micro hardness of dental tissues influenced by administration of aspirin during pregnancy / Microdureza de los tejidos dentales influenciada por la administración de aspirina durante el embarazo

The study is associated with the effect of aspirin (Acetyl Salicylic Acid) on the microhardness of mineralized tissues of the offspring's teeth, in response to the ingestion of the drug during pregnancy. Aspirin is a widely used analgesic and antipyretic medicine, for symptomatic treatment. Misuse of this drug during pregnancy may instigate developmental defects in offspring. An experimental control study was designed, in which female rabbits were taken as representative mammalian models and treated with aspirin during pregnancy. Their offspring's teeth were used to assess the microhardness of dental tissues. The rabbits were alienated into two groups, treated and control, consisting of seven rabbits in each set (n= 7). Microhardness was evaluated in three types of the sample teeth. The total number of teeth examined were, 2x7x12= 168 samples. Vicker's Hardness degree values were measured and recorded vis-à-vis (50 g for 15 s with 3 indentations per specimen on enamel and dentine separately). The range of hardness obtained was statistically analyzed and the Student's t-tests was applied, with the aid of SPSS version 20. The P-values for both enamel and dentine from maxillary incisors and molars were less than 0.05. The same trend was observed in the mandibular teeth. However, a teratogenicity of Acetyl Salicylic Acid was pragmatic in the recent in vivo studies. Based on the analysis, it was evident that the aspirin administration could produce negative effects leading to reduction in the microhardness of dental tissues of the offsprings.

El estudio asocia el efecto de la aspirina (ácido acetil salicílico) sobre la microdureza de los tejidos mineralizados de los dientes de crías, en respuesta a la ingesta del fármaco durante la preñez. La aspirina es un analgésico y antipirético ampliamente utilizado para el tratamiento sintomático. El mal uso de esta droga durante la preñez puede inducir defectos en el desarrollo de las crías. Se diseñó un estudio experimental de control, en el que se tomaron conejas como modelos de mamíferos representativos y fueron tratados con aspirina durante la preñez. Los dientes de sus crías fueron utilizados para evaluar la microdureza de los tejidos dentales. Los animales fueron distribuidos en dos grupos, tratados y control, con siete animales en cada grupo (n= 7). La microdureza se evaluó en tres tipos de dientes de la muestra. El número total de dientes examinados fueron 168 (2x7x12). Se midieron y registraron valores del grado de dureza Vickers vis-à-vis (50 g por 15 s con 3 indentaciones por especimen sobre el esmalte y la dentina por separado). Se analizó estadísticamente la gama de dureza obtenida y se aplicaron pruebas t de Student con la ayuda del programa SPSS versión 20. Los valores de p para el esmalte y la dentina de los incisivos maxilares y molares fueron menores a 0,05. Se observó la misma tendencia en los dientes mandibulares. Sin embargo, teratogenicidad producto del ácido acetil salicílico se encontró en recientes estudios in vivo. De acuerdo al análisis de los resultados, se evidenció que la administración de aspirina provocó efectos negativos que determinaron la reducción de la microdureza de los tejidos dentales de las crías.

Effect of ethanolic extracts of Justicia neesii Ramam. against experimental models of pain and pyrexia.

OBJECTIVE: The main objective of this study is to evaluate the analgesic and anti-pyretic activities of ethanolic extracts of Justicia neesii Ramam. by different experimental models. MATERIALS AND METHODS: The analgesic activity of plant extract was evaluated against thermal and chemical stimulus induced by Eddy's hot plate and acetic acid respectively in mice. Brewer's yeast induced pyrexia was used to evaluate the antipyretic activity in rats and TAB vaccine induced pyrexia was used to evaluate the antipyretic activity in rabbits. RESULTS: In the hot plate model 400 mg/kg p.o. dose of J. neesii has shown its maximal effect at 3 h. The results are significant (P < 0.05) and comparable to the values of standard drug pentazocine (30 mg/kg i.p.). In acetic acid induced writhing model 400 mg/kg p.o. of plant extracts have shown highly significant activity (P < 0.001) and better than standard drug indomethacin (10 mg/kg p.o.). The 400 mg/kg p.o. dose of plant extract has given significant results against both yeast induced pyrexia and TAB vaccine induced pyrexia (P< 0.01 and 0.05 respectively). These values are comparable to that of paracetamol 100 mg/kg p.o. standard dose. CONCLUSION: This study shows that the ethanol extract of J. neesii has significant analgesic and antipyretic activity.

Pharmacological and safety evaluation of fibrous root of Rhizoma Coptidis.

The aim of this study was to investigated the pharmacological activities and safety of fibrous root of Rhizoma Coptidis (FRC). FRC not only protected Kunming mice from the minimal lethal dose of Escherichia coli, but also protected rabbits from hyperpyrexia induced by lipopolysaccharid (LPS). The acute toxicity study showed that oral medial lethal dose (LD50) of FRC was greater than 7000mg/kg body weight in Kunming mice. The sub-chronic toxicity study showed that the no-observed-adverse effect level (NOAEL) of FRC was 1.88g/kg body weight in Sprague-Dawley rats, whereas FRC at higher dose (3.76g/kg body weight) resulted in damage to liver and lung. Negative results were present in Ames test, mouse micronucleus test and mouse sperm abnormality test. These finding support the use of FRC in veterinary medicine.