Our study observed gender-specific ibuprofen-mediated effects on mice liver. However, since the proteomic profiling was only done on male mice, the liver proteins and pathways investigated by Western blotting and biochemical assays were limited only to proteins which were identified as differentially regulated in liver of male mice.
It is likely that female-specific changes in protein expression also occur in ibuprofen treated livers and these changes were not investigated. The effects observed may also be age specific and could be significantly different in mice of different ages. Mass spectrometry showed that moderate levels of ibuprofen given to healthy mice for seven days resulted in over proteins that were significantly altered when compared to control groups.
Western blotting and biological assays showed that livers from male and female mice showed differences in the UPS, glycolysis and fatty acid metabolism. It is likely that many of the other pathways that were affected by ibuprofen also show gender differences, but these pathways were not investigated in this study. The data also suggests that ibuprofen affects previously unknown pathways such as amino acid, steroid and vitamin metabolism. Overall, our data indicate that moderate doses of ibuprofen can affect liver more significantly than previously reported and include proteasome dysfunction, increased levels of H 2 O 2 , impaired glycolytic pathways and altered fatty acid synthesis and oxidation.
Although we expected similar differences between males and females with respect to ibuprofen treatment, complex gender-specific ibuprofen-mediated effects were observed.
These gender-specific effects may be important for the side effects of ibuprofen such as increased risk of stroke and more research is needed to investigate this possibility. The amounts of ibuprofen taken by males and females may need to be altered in the future. Although the published experimental data to support that males and females show important physiological differences that affect the pathophysiology of many common diseases is increasing at a steady pace, very little gender-specific health care is utilized worldwide.
Ultimately, gender should be considered in drug use, as the toxicity of some drugs is significantly different between women and men. All Western Blot raw data generated or analyzed during this study are included in this published article Supplementary Figure 4. The datasets generated during the current study are available from the corresponding author on reasonable request.
Irvine, J. Formulation and delivery strategies of ibuprofen: challenges and opportunities. Dill, J. A molecular mechanism for ibuprofen-mediated RhoA inhibition in neurons. Rainsford, K. Ibuprofen: pharmacology, efficacy and safety.
Smyth, E. Prostanoids in health and disease. RJLR Chang, S. Mazaleuskaya, L. PharmGKB summary: ibuprofen pathways. Rui, L. Energy metabolism in the liver. Gao, Y. Proteomic analysis of acetaminophen-induced hepatotoxicity and identification of heme oxygenase 1 as a potential plasma biomarker of liver injury.
Article Google Scholar. Ghosh, R. Laster, J. Aspirin-Induced Acute Liver. ACG case Rep. Article PubMed Google Scholar. Wen, C. Metabolism of liver CYP and ultrastructural changes after long-term administration of aspirin and ibuprofen. Different effects of the nonsteroidal anti-inflammatory drugs meclofenamate sodium and naproxen sodium on proteasome activity in cardiac cells. Cell Cardiol.
Diclofenac induces proteasome and mitochondrial dysfunction in murine cardiomyocytes and hearts. Jamil, A. Ibuprofen targets neuronal pentraxins expresion and improves cognitive function in mouse model of AlCl3-induced neurotoxicity. Bendele, A.
Hepatocellular proliferation in ibuprofen-treated mice. Reagan-Shaw, S. Dose translation from animal to human studies revisited. Klotz, C. Rauniyar, N. III Isobaric labeling-based relative quantification in shotgun proteomics. Proteome Res. Ow, S. Gomes, A. Proteomic analysis of physiological versus pathological cardiac remodeling in animal models expressing mutations in myosin essential light chains.
Muscle Res. Cell Motil. Shadforth, I. Oberg, A. Cui, Z. Crude and purified proteasome activity assays are affected by type of microplate. Identification of the immunoproteasome as a novel regulator of skeletal muscle differentiation. Kimura, H. Cloos, J. Immuno proteasomes as therapeutic target in acute leukemia. Cancer Metastasis Rev.
Collins, G. The Logic of the 26S Proteasome. Dantuma, N. The ubiquitin-proteasome system in neurodegenerative diseases: precipitating factor, yet part of the solution. Ranek, M. Protein kinase g positively regulates proteasome-mediated degradation of misfolded proteins. Wong, H. Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions.
Veal, E. Hydrogen peroxide sensing and signaling. Scarim, C. Fong, S. Stamper, B. Proteomic analysis of acetaminophen-induced changes in mitochondrial protein expression using spectral counting.
Lee, C. Lapeyre-Mestre, M. Non-steroidal anti-inflammatory drug-related hepatic damage in France and Spain: analysis from national spontaneous reporting systems. Sgro, C. Incidence of drug-induced hepatic injuries: a French population-based study. Upadhyay, A. Janssen, G. Ibuprofen: Plasma Concentrations in Man. Lecker, S. Protein degradation by the ubiquitin-proteasome pathway in normal and disease states. Jamart, C. Regulation of ubiquitin-proteasome and autophagy pathways after acute LPS and epoxomicin administration in mice.
BMC Musculoskelet. Ebstein, F. Emerging roles of immunoproteasomes beyond MHC class I antigen processing. Launay, N. Oxidative stress regulates the ubiquitin-proteasome system and immunoproteasome functioning in a mouse model of X-adrenoleukodystrophy.
Nesari, A. Preadministration of high-dose alpha-tocopherol improved memory impairment and mitochondrial dysfunction induced by proteasome inhibition in rat hippocampus. Nguyen, A. PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis.
Zanella, A. Red cell pyruvate kinase deficiency: molecular and clinical aspects. Kemmelmeier, F. Effects of the nonsteroidal anti-inflammatory drug mefenamic acid on energy metabolism in the perfused rat liver. Garcia, M. Phosphofructokinase deficiency leads to a severe cardiac and hematological disorder in addition to skeletal muscle glycogenosis.
PLoS Genet. Mullarky, E. Nakao, N. Uemoto 3—23 Schutt, F. Moderately reduced ATP levels promote oxidative stress and debilitate autophagic and phagocytic capacities in human RPE cells. Zhao, R. Mitochondrial electron transport chain, ROS generation and uncoupling Review. Bhatia, K.
Oxidative stress contributes to sex differences in angiotensin II-mediated hypertension in spontaneously hypertensive rats. Barp, J. Myocardial antioxidant and oxidative stress changes due to sex hormones. Johnson, T. Zheng, X. Alleviation of neuronal energy deficiency by mTOR inhibition as a treatment for mitochondria-related neurodegeneration. Huang, H. Physiological levels of ATP negatively regulate proteasome function. Cell Res. Bolanos, J. Bioenergetics and redox adaptations of astrocytes to neuronal activity.
Seo, E. Reactive oxygen species-induced changes in glucose and lipid metabolism contribute to the accumulation of cholesterol in the liver during aging. Porter, S. Non-steroidal anti-inflammatory drugs and apoptosis in the gastrointestinal tract: potential role of the pentose phosphate pathways. Kourounakis, A. Chang, H. Clinical use of cyclooxygenase inhibitors impairs vitamin B-6 metabolism.
However, use in the third trimester of pregnancy has been cautioned against by some and as NSAIDs are used closer to term, risks to mother and child increase. In children, NSAIDs are considered to be just as safe as acetaminophen, with the main risk being dosing errors. While ibuprofen has been shown to be highly effective as an analgesic, a ceiling dose has been noted by some researchers.
As a result, supplemental analgesics to be taken in conjunction with ibuprofen have been advocated as a way to increase analgesia, such as concomitant administration of acetaminophen, which results in a statistically significant decrease in discomfort compared to mg ibuprofen alone Menhinick, , IEJ.
A quantitative systemic review found that the combination of ibuprofen and acetaminophen provided greater analgesic efficacy than opioids, as well as fewer adverse effects Moore, , JADA. With its tried and proven efficacy, it is easy to see why ibuprofen is one of the analgesics of choice by endodontists.
Falcon is an assistant professor in the Department of Endodontics at Rutgers, where she also completed her dental degree and endodontic training. She can be reached at falconcy sdm. Read more in Pharmacology. Acetaminophen and ibuprofen are available in every pharmacy. GoodRx can give you an idea of specific prices in stores near you. The side effects of acetaminophen and ibuprofen may differ. This is because your body breaks them down differently.
For example, acetaminophen is broken down and removed by the liver. Acetaminophen has a warning about liver damage it can cause that can be fatal cause death. Liver damage can happen if you take too much in a hour period.
For more information, read about the dangers of acetaminophen overdose. Ibuprofen, on the other hand, is removed from your body by your kidneys. Taking it for a long time can cause kidney damage and stomach bleeding. Using high doses of ibuprofen for longer than recommended can increase your risk of:. Acetaminophen and ibuprofen can cause dangerous interactions when you take them with certain medications. To reduce your risk, make sure you tell your doctor about all drugs, supplements, and herbs you take.
Taking either acetaminophen or ibuprofen may cause problems if you have certain health issues. Talk to your doctor before using acetaminophen or ibuprofen if you have:. Acetaminophen and ibuprofen both treat pain, but they work slightly differently in your body. Each drug can pose different safety issues, especially if you have existing health conditions.
How different can they be? Learn more to judge for yourself. Over-the-counter anti-inflammatory drugs help reduce pain.
0コメント