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Medical Forum / Diseases and Disorders / Hepatitis / May 2008NEWS: Aspirin Reduces HCV Load
Acetylsalicylic acid inhibits hepatitis C virus RNA and protein expression through cyclooxygenase 2 signaling pathways. Trujillo-Murillo K, Rincón-Sánchez AR, Martínez-Rodríguez H, Bosques-Padilla F, Ramos-Jiménez J, Barrera-Saldaña HA, Rojkind M, Rivas-Estilla AM. Department of Biochemistry, School of Medicine and University Hospital, Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon, Mexico. It has been reported that salicylates (sodium salicylate and aspirin) inhibit the replication of flaviviruses, such as Japanese encephalitis virus and dengue virus. Therefore, we considered it important to test whether acetylsalicylic acid (ASA) had anti-hepatitis C virus (HCV) activity. To this end, we examined the effects of ASA on viral replication and protein expression, using an HCV subgenomic replicon cell culture system. We incubated Huh7 replicon cells with 2-8 mM ASA for different times and measured HCV-RNA and protein levels by northern blot, real-time polymerase chain reaction, and western analysis, respectively. We found that ASA had a suppressive effect on HCV-RNA and protein levels (nearly 58%). ASA-dependent inhibition of HCV expression was not mediated by the 5'-internal ribosome entry site or 3'-untranslated regions, as determined by transfection assays using bicistronic constructs containing these regulatory regions. However, we found that HCV-induced cyclooxygenase 2 (COX-2) messenger RNA and protein levels and activity and these effects were down-regulated by ASA, possibly by a nuclear factor kappa B-independent mechanism. We also observed that the ASA-dependent inhibition of viral replication was due in part to inhibition of COX-2 and activation of p38 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 (MEK1/2) mitogen-activated protein kinases (MAPKs). Inhibition of these kinases by SB203580 and U0126, respectively, and by short interfering RNA silencing of p38 and MEK1 MAPK prevented the antiviral effect of ASA. Taken together, our findings suggest that the anti-HCV effect of ASA in the Huh7 replicon cells is due to its inhibitory effect on COX-2 expression, which is mediated in part by the activation of MEK1/2/p38 MAPK. CONCLUSION: These findings suggest the possibility that ASA could be an excellent adjuvant in the treatment of chronic HCV infection.  SignatureTo reach me, complete my last name in the address. Thomas, This is quite interesting. Remember Sulfasalazine? Someone from outside the usual correspondents on this list, when informed that perhaps Sulfasalzine could aid in reducing or reversing fibrosis damage, responded "too bad that it is bound with Aspirin..." or words to that effect. This gets one wondering... as if I ever stop wondering... Thanks cactus jammies > Acetylsalicylic acid inhibits hepatitis C virus RNA and protein > expression through cyclooxygenase 2 signaling pathways. [quoted text clipped - 34 lines] > possibility that ASA could be an excellent adjuvant in the treatment of > chronic HCV infection. On May 5, 1:23 pm, "Cactus Jammies" <cactusjamm...@retinal.circus.orb> wrote: > Thomas, > This is quite interesting. Remember Sulfasalazine? Someone from outside [quoted text clipped - 6 lines] > > cactus jammies Jammy Man, When I was first dx'd with HCV in 1998 I went over to the U of P in Philadelphia. I met a girl there who just finished a trial with Interferon and with Ketoprofen. It was her second try but she cleared. I'm not sure even if they were using Riba with it back then. It seemed odd to me at the time because Ketoprofen is a NSAID but then I was new to HCV and knew very little at that time, even as a nurse. It's funny how you ponder something and years down the road you find the interstate............ never stop wondering..........yikes that was 10 years ago. eileen <~~~~~~~~~~~~~ a crumpled cookie but clear at 6 months post treatment. > > Acetylsalicylic acid inhibits hepatitis C virus RNA and protein > > expression through cyclooxygenase 2 signaling pathways. [quoted text clipped - 38 lines] > > - Show quoted text - LET'S HEAR IT FOR EILEEN, THE DRAGON SLAYER! way to go Eileen :) I am so happy to read that news! and you'll keep getting better day by day, I know you will. lotsa hugs Sara On May 5, 1:23 pm, "Cactus Jammies" <cactusjamm...@retinal.circus.orb> wrote: > Thomas, > This is quite interesting. Remember Sulfasalazine? Someone from [quoted text clipped - 10 lines] > > cactus jammies Jammy Man, When I was first dx'd with HCV in 1998 I went over to the U of P in Philadelphia. I met a girl there who just finished a trial with Interferon and with Ketoprofen. It was her second try but she cleared. I'm not sure even if they were using Riba with it back then. It seemed odd to me at the time because Ketoprofen is a NSAID but then I was new to HCV and knew very little at that time, even as a nurse. It's funny how you ponder something and years down the road you find the interstate............ never stop wondering..........yikes that was 10 years ago. eileen <~~~~~~~~~~~~~ a crumpled cookie but clear at 6 months post treatment. > "Thomas Wagner" <t...@capecod.com> wrote in message > [quoted text clipped - 73 lines] > > - Show quoted text - > LET'S HEAR IT FOR EILEEN, THE DRAGON SLAYER! > [quoted text clipped - 124 lines] > > - Show quoted text - Thanks Sara, Couldn't have done it without our cookies! Waiting on my new Detroit Music you promised. You above all others have been my cheerleader, Thank You. Now we need to see more of the cookies. ;) eileen [...] >eileen <~~~~~~~~~~~~~ a crumpled cookie but clear at 6 months post >treatment. So *that* is the way the cookie crumples! :-) Excellent news, Eileen! Glad to hear this! Cheers! (and <golf claps!>) /greyhackles > [...] > [quoted text clipped - 8 lines] > > /greyhackles Thanks Grey As usual your contributions to everyone here is so valuable. I ThankYou for your kindness to me and sharing your knowledge with all. eileen >On May 5, 1:23 pm, "Cactus Jammies" <cactusjamm...@retinal.circus.orb> >wrote: [quoted text clipped - 22 lines] >eileen <~~~~~~~~~~~~~ a crumpled cookie but clear at 6 months post >treatment. fwiw: It appears the most recent trial combining Interferon with Ketoprofen was conducted in 2003, comparing that combo with Interferon monotherapy. SVR rates were roughly tripled with that combo vs IFN monotherapy (32.5% vs 10%). Issues with epigastric pain was significantly higher with the combo therapy (as one might imagine). Thumbnail here: http://www.blackwell-synergy.com/doi/abs/10.1046/j.1365-2893.2003.00449.x?journa lCode=jvh Going back in time, this study published in 1999 also showed roughly triple the SVR rates with Interferon + Ketoprofen vs IFN Monotherapy (26% vs 10%) while pointing out potential NSAID hepatotoxicity with the Ketoprofen: http://gut.bmj.com/cgi/content/abstract/46/3/427 Published the same year, this study showed no significant difference in SVR rates for Interferon w/or wo Ketoprofen (in fact the without arm did slightly better): http://www.blackwell-synergy.com/doi/pdf/10.1046/j.1365-2036.1999.00613.x And this study using IFN + Ketoprofen on previous IFN monotherapy non-responders showed zero success: http://www.ncbi.nlm.nih.gov/pubmed/9218853 So it looks like Ketoprofen was relegated to the dustbin when Peg-IFN + Ribavirin studies showed far better results... /greyhackles > Jammy Man, > [quoted text clipped - 9 lines] > eileen <~~~~~~~~~~~~~ a crumpled cookie but clear at 6 months post > treatment. Eileen, glad to hear the news. Dwight > > Jammy Man, > [quoted text clipped - 13 lines] > > Dwight Dwight, Dwight! Always there giving me help, without ever knowing you made my day! Hope the new house is everything your gang and zoo need. eileen >eileen <~~~~~~~~~~~~~ a crumpled cookie but clear at 6 months post >treatment. Congrats on the SVR! A costly one but I'll bet over time things will improve. Don > >eileen <~~~~~~~~~~~~~ a crumpled cookie but clear at 6 months post > >treatment. [quoted text clipped - 3 lines] > > Don Don, I am kook oz u re ? do I have it right? Thanks for your cheerleading too, it means alot. eileen Somebody want to translate that for me? I've got brain fog. > Acetylsalicylic acid inhibits hepatitis C virus RNA and protein > expression through cyclooxygenase 2 signaling pathways. [quoted text clipped - 34 lines] > possibility that ASA could be an excellent adjuvant in the treatment of > chronic HCV infection. > Somebody want to translate that for me? I've got brain fog. Hi Thip, The bottom line is what you want to look for in these abstracts. In the orginal posting (see below) the scientists posited that ASA looks promising as an adjuvant in concert with treatments as they are. Adjuvants are frequently used in some types of Cancer therapies. - cactus jammies Adjuvant From Wikipedia, the free encyclopedia Adjuvants are pharmacological or immunological agents that modify the effect of other agents (e.g., drugs, vaccines) while having few if any direct effects when given by themselves. In this sense, they are roughly analogous to chemical catalysts. Types of adjuvants include: a.. Pharmaceutic adjuvant b.. In pharmacology, adjuvants are drugs that have few or no pharmacological effects by themselves, but may increase the efficacy or potency of other drugs when given at the same time. c.. Immunologic adjuvant d.. Agricultural spray adjuvant e.. Adjuvant chemotherapy f.. Adjuvants for dermatalogical products, including cosmetics and toiletries >> CONCLUSION: These findings suggest the >> possibility that ASA could be an excellent adjuvant in the treatment of >> chronic HCV infection. Well, durn it all, CJ. And here I thought you were gonna tell me I'd live a normal life span if I ate half a bottle of aspirin every day. :-) Thanks for the info, friend. >> Somebody want to translate that for me? I've got brain fog. > [quoted text clipped - 26 lines] >>> possibility that ASA could be an excellent adjuvant in the treatment of >>> chronic HCV infection. >Well, durn it all, CJ. And here I thought you were gonna tell me I'd live a >normal life span if I ate half a bottle of aspirin every day. :-) That and about 10 or so grapefruits a day just might be the answer. As long as you are diligent with the bloodletting that is. Don >>Well, durn it all, CJ. And here I thought you were gonna tell me I'd live >>a [quoted text clipped - 4 lines] > > Don Set up a regimen and I'll see if I can find a test sucker--um, make that a test subject--to try it out. Don't forget not to miss any doses of the Laetrile, as well... :) >> Well, durn it all, CJ. And here I thought you were gonna tell me I'd live a >> normal life span if I ate half a bottle of aspirin every day. :-) [quoted text clipped - 3 lines] > > Don
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