Protective Effects of Acetaminophen on Ibuprofen-Induced Gastric Mucosal Damage in Rats with Associated Suppression of Matrix Metalloproteinase

Islam

Evidence-Based Complementary and Alternative Medicine

et al. 2019

The stem bark of Oroxylum indicum (O. indicum) was aimed at testing for anti-inflammatory, antiulcerative, antihyperglycemic, and antidyslipidemic activities. Liver enzyme concentration (SGPT, SGOT) had also been assessed. After being extracted in organic solvent, 3 distinct doses, 100, 200, and 400 mg/kg b.w. (p.o.), were used. For edema formation 0.1 ml carrageenan at a dose of 1% w/v was injected into paw of left hind. It showed a fall of edemas 37.50%, 48.34%, and 55.83% while used doses were 100, 200, and 400 mg/kg b.w. (p.o.) individually. The EtOH extract of O. indicum (50%) and its fractions PET, CLF, EtOAc, and nBUT were studied against ethanol-induced gastric mucosal damage. Only PET and n-BuOH exhibited the highest percentage of protection and were 96% and 99%, respectively, persuaded by ethanol. In OGTT glibenclamide revealed reduction of glucose level to 7.55 ± 0.22 mmol/L from 10.57 ± 0.32 mmol/L after 30 minutes. Antihyperglycemic activities were assessed for 8- and 12-week duration in diabetic rats. Glibenclamide reduced glucose level from 33.50±0.31 to 7.90±0.19 mmol/L in 12 weeks. In 12 and 8 weeks, combination therapy lowered blood glucose level to a normal extent by 79% and 61% individually. In antidyslipidemic activities after 12-week treatment, it revealed simvastatin; MEOI (400 mg/kg b.w.) and combination of both reduced TC level by 44%, 28%, and 48% consequently followed by TG and LDL. In 8-week treatment, HDL levels were increased by 34%, 13%, and 36%, and in 12 weeks increased by 36%, 8%, and 38% consequently. Liver enzyme concentration after 12 weeks of treatment with glibenclamide, 400 mg/kg b.w. (p.o.) of MEOI and combination of both, exhibited the fact that concentration of SGPT showed downturn by 43.23%, 8.01%, and 54.86% and SGOT by 42.40%, 5.31%, and 44.85%. This study remarked that O. indicum has anti-inflammatory, antiulcer, antidiabetic, and antidyslipidemic potentials but has no ameliorative effect on liver enzyme.

Section: Discussionsupporting

confidence: 92%

Ethnopharmacological Inspections of Organic Extract ofOroxylum indicumin Rat Models: A Promising Natural Gift

Islam

Evidence-Based Complementary and Alternative Medicine

et al. 2019

Journal of Pharmacology and Experimental Therapeutics

“…RNA isolation, cDNA synthesis, and quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) were performed as described in the online Supplemental Material and described by Linder et al (2010) and Fukushima et al (2014).…”

Section: Methodsmentioning

confidence: 99%

Involvement of Extracellular Signal-Regulated Kinase 5 in Kinin B1 Receptor Upregulation in Isolated Human Umbilical Veins

Kilstein

Nowak

Errasti

et al. 2016

The upregulated kinin B 1 receptors exert a pivotal role in modulating inflammatory processes. In isolated human umbilical veins (HUVs), kinin B 1 receptor is upregulated as a function of in vitro incubation time and proinflammatory stimuli. The aim of this study was to evaluate, using functional and biochemical methods, the involvement of extracellular signal-regulated kinase 5 (ERK5), p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK1/ 2) on the kinin B 1 receptor upregulation process in HUV. Real-time polymerase chain reaction analysis revealed for the first time that kinin B 1 receptor mRNA expression closely parallels the functional sensitization to kinin B 1 receptor selective agonist des-Arg 10 -kallidin (DAKD) in HUV. Moreover, the selective inhibition of ERK5, p38 MAPK, and JNK, but not ERK1/2, produced a dosedependent rightward shift of the concentration-response curves to DAKD after 5-hour incubation and a reduction in kinin B 1 receptor mRNA expression. Biochemical analyses showed that ERK5, p38 MAPK, and JNK phosphorylation is maximal during the first 2 hours postisolation, followed by a significant reduction in the last 3 hours. None of the treatments modified the responses to serotonin, an unrelated agonist, suggesting a specific effect on kinin B 1 receptor upregulation. The present work provides for the first time pharmacologic evidence indicating that ERK5 plays a significant role on kinin B 1 receptor upregulation. Furthermore, we confirm the relevance of p38 MAPK and JNK as well as the lack of effect of ERK1/2 in this process. This study may contribute to a better understanding of MAPK involvement in inflammatory and immunologic diseases.

“…Neben der Hemmung der Cyclooxygenase spielt auch der Einfluss von Ibuprofen auf die Metalloproteinase MMP-13 eine wesentliche Rolle in der Schädigung der Magenschleimhaut. Eine Suppression von MMP-13 durch Acetaminophen verminderte im Tierexperiment die durch Ibuprofen hervorgerufenen Schleimhautschäden im Magen [9]. Ibuprofen und auch Naproxen nicht nachgewiesen werden [10].…”

Section: Pns-nozizeptorunclassified

Wirkung und Nebenwirkungen von Ibuprofen

Jahn

2017

Phys Med Rehab Kuror

ZusammenfassungIbuprofen ist ein weit verbreitetes nichtsteroidales Antiphlogistikum (NSAID). Es hemmt durch Blockade des aktiven Zentrums die Cyclooxygenase 1 und 2 (COX-1 und COX-2) reversibel. In höheren Konzentrationen als die zur Hemmung der COX-1 und COX-2 notwendig sind, zeigt es Antitumor-Aktivität. In OTC-Dosierung (over the counter) (<1200 mg/d) ist das Risiko zur Entstehung von gastrointestinalen Blutungen geringer als bei Diclofenac, Naproxen, Piroxicam oder Indomethacin. Mit Erhöhung der Dosis (2400–3200 mg/d) und Verlängerung der Therapiedauer steigt das Risiko für gastrointestinale Nebenwirkungen. Bei höheren Dosierungen und schon eingeschränkter Nierenfunktion kann Ibuprofen zu einem akuten Nierenversagen führen. Eine Kontrolle der Nierenfunktion ist in diesen Fällen angezeigt. Bei Kindern bis zu 12 Jahren, bei Schwangeren und auch älteren Patienten sollte Paracetamol der Vorzug gegeben werden. Patienten mit Hypertonie, welche mit ACE-Hemmern, Angiotensin-II-Rezeptorenblockern oder Thiazid-Diuretika behandelt werden, sollten Ibuprofen nicht über einen längeren Zeitraum einnehmen. Bei gleichzeitiger Einnahme von Ibuprofen und Acetylsalicylsäure wird die irreversible Hemmung von ASS auf die COX-1 vermindert, da Ibuprofen eine höhere Affinität zum aktiven Zentrum der COX-1 besitzt.Eine kurzzeitige Behandlung mit Ibuprofen ist meist unproblematisch. Bei längerfristiger Therapie und höherer Dosierung muss zwischen niedrigem und hohem gastrointestinalem und kardiovaskulärem Risiko differenziert werden.