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Aspirin (Acetylsalicylic Acid) Inhibits HCV Replication in Laboratory Study
Aspirin (Acetylsalicylic Acid) Inhibits HCV Replication in Laboratory Study
http://www.hivandhepatitis.com/hep_c/news/2008/062008_a.html
Aspirin (Acetylsalicylic Acid) Inhibits HCV Replication in Laboratory Study
Due to the limitations of interferon-based therapy for chronic hepatitis C virus (HCV) infection, researchers have explored various alternative therapies. In the May 2008 issue of Hepatology, Mexican researchers reported on a laboratory study of the anti-HCV activity of acetylsalicylic acid, better known as aspirin.
The investigators were interested in testing acetylsalicylic acid against HCV because it has previously been reported that salicylates inhibit the replication of other flaviviruses including Japanese encephalitis virus and dengue virus.
In the present study, the researchers examined the effects of acetylsalicylic acid on viral replication and protein expression using an HCV subgenomic replicon cell culture system. They incubated Huh7 replicon cells with 2-8 mM acetylsalicylic acid for different durations, and measured HCV RNA and protein levels using Northern blot, Western blot, and real-time polymerase chain reaction (PCR) assays.
Results
• Acetylsalicylic acid had a suppressive effect on HCV RNA and protein levels of nearly 58%.
• Acetylsalicylic acid-dependent inhibition of HCV expression was not mediated by the 5'-internal ribosome entry site or 3'-untranslated regions.
• However, HCV-induced cyclooxygenase 2 (COX-2) messenger RNA and protein levels and activity were down-regulated by acetylsalicylic acid, possibly via a nuclear factor kappa-B (NF-kappa-B)-independent mechanism.
• Acetylsalicylic acid-dependent inhibition of viral replication was due in part to inhibition of COX-2 and activation of p38 and MEK1/2 mitogen-activated protein kinases (MAPKs).
• Inhibition of these kinases, for example by short interfering RNA silencing, blocked the antiviral effect of acetylsalicylic acid.
The investigators concluded that, "our findings suggest that the anti-HCV effect of acetylsalicylic acid 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."
These findings, they added, "suggest the possibility that acetylsalicylic acid could be an excellent adjuvant in the treatment of chronic HCV infection."
6/20/08
Reference
K Trujillo-Murillo, AR Rincon-Sanchez, H Martinez-Rodriguez, and others. Acetylsalicylic acid inhibits hepatitis C virus RNA and protein expression through cyclooxygenase 2 signaling pathways. Hepatology 47(5): 1462-1472. May 2008.
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My comments (and others are welcomed) they don't mention just how much asprin that one might take or the frequency. For instance a half asprin a day can reduce the chance of a heart attack. What kind of doing is required to achieve the levels needed for this to work?
People should note, moderate use of asprin[i] could[/i] raise LFT's, could increase thinning of the blood thereby reducing it's ability to clot.
People with advanced liver disease need to check with their doctors before deciding to self medicate with asprin. Hypertension, varices, diminished clortting ability common with many people with advanced liver disease makes consultaion with a doctor more important. Check with your doctor FIRST!!!
There are a number of compounds which are showing some promise in inhibiting HCV replication. Grapefruit juice is also shown to reduce HCV replication.
Best,
Willy
http://www.hivandhepatitis.com/hep_c/news/2008/062008_a.html
Aspirin (Acetylsalicylic Acid) Inhibits HCV Replication in Laboratory Study
Due to the limitations of interferon-based therapy for chronic hepatitis C virus (HCV) infection, researchers have explored various alternative therapies. In the May 2008 issue of Hepatology, Mexican researchers reported on a laboratory study of the anti-HCV activity of acetylsalicylic acid, better known as aspirin.
The investigators were interested in testing acetylsalicylic acid against HCV because it has previously been reported that salicylates inhibit the replication of other flaviviruses including Japanese encephalitis virus and dengue virus.
In the present study, the researchers examined the effects of acetylsalicylic acid on viral replication and protein expression using an HCV subgenomic replicon cell culture system. They incubated Huh7 replicon cells with 2-8 mM acetylsalicylic acid for different durations, and measured HCV RNA and protein levels using Northern blot, Western blot, and real-time polymerase chain reaction (PCR) assays.
Results
• Acetylsalicylic acid had a suppressive effect on HCV RNA and protein levels of nearly 58%.
• Acetylsalicylic acid-dependent inhibition of HCV expression was not mediated by the 5'-internal ribosome entry site or 3'-untranslated regions.
• However, HCV-induced cyclooxygenase 2 (COX-2) messenger RNA and protein levels and activity were down-regulated by acetylsalicylic acid, possibly via a nuclear factor kappa-B (NF-kappa-B)-independent mechanism.
• Acetylsalicylic acid-dependent inhibition of viral replication was due in part to inhibition of COX-2 and activation of p38 and MEK1/2 mitogen-activated protein kinases (MAPKs).
• Inhibition of these kinases, for example by short interfering RNA silencing, blocked the antiviral effect of acetylsalicylic acid.
The investigators concluded that, "our findings suggest that the anti-HCV effect of acetylsalicylic acid 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."
These findings, they added, "suggest the possibility that acetylsalicylic acid could be an excellent adjuvant in the treatment of chronic HCV infection."
6/20/08
Reference
K Trujillo-Murillo, AR Rincon-Sanchez, H Martinez-Rodriguez, and others. Acetylsalicylic acid inhibits hepatitis C virus RNA and protein expression through cyclooxygenase 2 signaling pathways. Hepatology 47(5): 1462-1472. May 2008.
-------------------------------------------------------------------
My comments (and others are welcomed) they don't mention just how much asprin that one might take or the frequency. For instance a half asprin a day can reduce the chance of a heart attack. What kind of doing is required to achieve the levels needed for this to work?
People should note, moderate use of asprin[i] could[/i] raise LFT's, could increase thinning of the blood thereby reducing it's ability to clot.
People with advanced liver disease need to check with their doctors before deciding to self medicate with asprin. Hypertension, varices, diminished clortting ability common with many people with advanced liver disease makes consultaion with a doctor more important. Check with your doctor FIRST!!!
There are a number of compounds which are showing some promise in inhibiting HCV replication. Grapefruit juice is also shown to reduce HCV replication.
Best,
Willy
Just in case MH trash the link the article is from Medscape and called
The Roles of Amantadine, Rimantadine, Ursodeoxycholic Acid, and NSAIDs, Alone or in Combination With Alpha Interferons, in the Treatment of Chronic Hepatitis C
Article No. 416610
CS
The Roles of Amantadine, Rimantadine, Ursodeoxycholic Acid, and NSAIDs, Alone or in Combination With Alpha Interferons, in the Treatment of Chronic Hepatitis C
Article No. 416610
CS
This has been tried before and didnt work. Intesesting that someone decided to have another look at it.
From http://www.medscape.com/viewarticle/416610_4
Nonsteroidal Anti-Inflammatory Drugs
Background and Pharmacology
The first report on the use of NSAIDs to treat chronic hepatitis C was published in 1993.[28] The rationale for the use of NSAIDs in treating chronic hepatitis C is based on their ability to inhibit prostaglandin synthesis, thereby potentially increasing the concentration of 2'5'oligoadenylate synthetase, an enzyme associated with the antiviral activity of interferon.[28] Most studies have used NSAIDs such as tenoxicam, ketoprofen, and aspirin (Figure 1) in combination with alpha interferons.[29-31] Although beneficial effects were initially reported using these combination therapies, the most rigorously designed study using tenoxicam in combination with alpha interferon failed to confirm these results.[29]
Nonsteroidal Anti-inflammatory Drugs Plus Alpha Interferon Therapy
The results of two studies employing NSAIDs in combination with alpha interferons are summarized in Table 3.[29,30] In a randomized, double-blind study of 149 alpha interferon-naive patients, Zarski et al[29] treated all patients with rIFN-alpha2a 3 MIU TIW in combination with either placebo or tenoxicam 20 mg/day. A biochemical ETR was observed in 49.3% of patients in the rIFN-alpha2a/placebo group and in 42.9% of patients in the combination rIFN-alpha2a/tenoxicam group. Six months after treatment cessation, biochemical response rates had decreased to 28.3% and 23.8% of patients, respectively. Similar to sustained biochemical response rates, sustained virologic response rates were virtually identical between treatments (17.2% and 17.5%, respectively). A 65% reduction in the Knodell Histologic Activity Index score was noted in the placebo group, compared with a 51% reduction in the group receiving combination rIFN-alpha2a/tenoxicam. These results show that the addition of tenoxicam to the regimen of rIFN-alpha2a did not result in further improvement in biochemical, virologic, or histologic parameters in chronic hepatitis C patients. In a separate study of rIFN-alpha2b (3 MIU TIW) plus ketoprofen (100 mg TID) for 4 months in alpha interferon nonresponders, no sustained biochemical or virologic responses were observed.[30]
Adverse Events
The incidence figures for most adverse events were similar between patients treated with alpha interferon monotherapy and those treated with combination alpha interferon/tenoxicam therapy; however, 2/73 (3%) patients receiving tenoxicam developed gastric ulcers that required medical intervention.[30]
Summary
Although the combination therapy of alpha interferons with NSAIDs is theoretically attractive, the results of a well-designed study failed to demonstrate any clinical benefit. Importantly, a relatively high incidence of gastric ulcerations requiring treatment has been reported, which is consistent with the known adverse events of NSAIDs.
CS
From http://www.medscape.com/viewarticle/416610_4
Nonsteroidal Anti-Inflammatory Drugs
Background and Pharmacology
The first report on the use of NSAIDs to treat chronic hepatitis C was published in 1993.[28] The rationale for the use of NSAIDs in treating chronic hepatitis C is based on their ability to inhibit prostaglandin synthesis, thereby potentially increasing the concentration of 2'5'oligoadenylate synthetase, an enzyme associated with the antiviral activity of interferon.[28] Most studies have used NSAIDs such as tenoxicam, ketoprofen, and aspirin (Figure 1) in combination with alpha interferons.[29-31] Although beneficial effects were initially reported using these combination therapies, the most rigorously designed study using tenoxicam in combination with alpha interferon failed to confirm these results.[29]
Nonsteroidal Anti-inflammatory Drugs Plus Alpha Interferon Therapy
The results of two studies employing NSAIDs in combination with alpha interferons are summarized in Table 3.[29,30] In a randomized, double-blind study of 149 alpha interferon-naive patients, Zarski et al[29] treated all patients with rIFN-alpha2a 3 MIU TIW in combination with either placebo or tenoxicam 20 mg/day. A biochemical ETR was observed in 49.3% of patients in the rIFN-alpha2a/placebo group and in 42.9% of patients in the combination rIFN-alpha2a/tenoxicam group. Six months after treatment cessation, biochemical response rates had decreased to 28.3% and 23.8% of patients, respectively. Similar to sustained biochemical response rates, sustained virologic response rates were virtually identical between treatments (17.2% and 17.5%, respectively). A 65% reduction in the Knodell Histologic Activity Index score was noted in the placebo group, compared with a 51% reduction in the group receiving combination rIFN-alpha2a/tenoxicam. These results show that the addition of tenoxicam to the regimen of rIFN-alpha2a did not result in further improvement in biochemical, virologic, or histologic parameters in chronic hepatitis C patients. In a separate study of rIFN-alpha2b (3 MIU TIW) plus ketoprofen (100 mg TID) for 4 months in alpha interferon nonresponders, no sustained biochemical or virologic responses were observed.[30]
Adverse Events
The incidence figures for most adverse events were similar between patients treated with alpha interferon monotherapy and those treated with combination alpha interferon/tenoxicam therapy; however, 2/73 (3%) patients receiving tenoxicam developed gastric ulcers that required medical intervention.[30]
Summary
Although the combination therapy of alpha interferons with NSAIDs is theoretically attractive, the results of a well-designed study failed to demonstrate any clinical benefit. Importantly, a relatively high incidence of gastric ulcerations requiring treatment has been reported, which is consistent with the known adverse events of NSAIDs.
CS
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