Findings from a recent study offer evidence that popular impotence medications may be able to protect the liver from the damage that can be caused by sepsis, a systemic inflammatory response to infection. This could be yet another example of the emerging versatility of PDE5 inhibitors, the family of drugs that has revolutionized the treatment of erection problems.
This most recent study, published in an issue of Science Signaling, is based on testing done by researchers at the University of Pittsburgh School of Medicine. Lead investigator on the study was Timothy Billiar, M.D., professor and chairman of surgery at the medical school.
Significance of Findings
In explaining the significance of the study’s findings, Dr. Billiar pointed out that infection anywhere in the body can trigger a release of chemicals that cause inflammation throughout the body, a condition known as sepsis. This condition, a leading cause of death in hospital intensive care units, can inflict life-threatening damage to vital organs, including the liver and kidneys.
“Sepsis is a very challenging problem, so the possibility that we might be able to repurpose a drug that is in use and well understood is very exciting,” Dr. Billiar said.
To better understand how sepsis works and the potential damage it can cause, it’s important to know that this inflammatory condition triggers the production of a protein known as tumor necrosis factor, or TNF. On the one hand, TNF helps to fight infection, while on the other, it can be harmful to vital organs at sustained high levels.
Mouse Models of Sepsis
The researchers at Pitt’s School of Medicine looked at the effects of sildenafil, better known as Viagra, in mouse models of sepsis and also in laboratory tests on human liver cells. In mice, they found that sildenafil caused the liver to produce greater amounts of a protein known as cyclic guanosine monophosphate, or cGMP. It’s worth noting that cGMP is a key player in facilitating the erection process.
In the mice, the increase in cGMP levels caused liver cells to shed surface proteins known as TNF receptors. As the number of receptor cells declined, the negative effects of TNF declined, protecting the liver from serious damage. Researchers also observed sildenafil’s protective effects in laboratory testing with human liver cells.
“Our study suggests that increasing the bioavailability of cyclic GMP might be beneficial in ameliorating the inflammation associated with sepsis,” Dr. Billiar said. “Sildenafil and other ED drugs might be a good approach to try early in the course of the illness to forestall organ damage.”
As a next step, Pitt researchers plan to try to replicate their findings in a large animal model of sepsis.
Growing List of Benefits
If subsequent testing proves that PDE5 inhibitors can successfully protect human livers from sepsis-inflicted damage, it will add to the growing list of these drugs’ medicinal benefits above and beyond facilitating the erectile process in impotent men.
A flurry of studies over the last decade has uncovered evidence that PDE5 inhibitors may also be effective in fighting various forms of cancer. One of the more recent findings came from a study conducted by researchers at Virginia Commonwealth University in Richmond.
In the VCU study, researchers found that combination therapy with sildenafil and an anticancer drug known as OSU-03012 (AR-12) was more effective in killing brain cancer cells than therapy using only the anticancer drug. Phil Dent, Ph.D., lead author of the VCU study, explained that together the two drugs are more effective at destabilizing a chaperone protein known as GRP78. Destabilization of GRP78 and minimizing chaperone function, says Dent, ¨kills brain cancer cells, including stem cell selected variants.¨
Could Fight Viral, Bacterial Illnesses
Apart from its potential application in treating certain types of cancer, the VCU findings could lead to new methods to fight a wide array of other viral and bacterial illnesses, according to an article posted at DailyMail.com. Such illnesses might include Ebola, hepatitis, influenza, and MRSA (methicillin-resistant Staphylococcus aureus).
Dent told the Daily Mail that findings from the VCU study ¨prove that GRP78 is a ‘drugable’ target to stop viruses from reproducing and spreading. And in the case of bacteria, we have a new antibiotic target, DnaK, that if we’re careful and only use the OSU drug in hospitals, we’ve got something that can help to treat the superbugs.¨
Meanwhile, researchers at Johns Hopkins Kimmel Cancer Center have conducted multiple studies over the last decade to look at ways in which the body’s immune system can better identify cancer cells and attack them. In late 2006, researchers reported that sildenafil by itself helped to somehow unmask malignant cells in animal studies. In laboratory mice with implanted breast and colon tumors, tumors were reduced two- or threefold in animals treated with sildenafil, compared with those who didn’t get the drug.
Elevated Levels of Nitric Oxide
In explanation for this phenomenon, Johns Hopkins researchers said it appeared that the elevated levels of nitric oxide triggered by sildenafil seem ¨to dampen the effects of a specialized cell that diverts the immune system away from tumors, allowing swarms of cancer-attacking T-cells to migrate to tumor sites in the rodents.¨
Those specialized cells targeted by Johns Hopkins researchers are known as myeloid-derived suppressor cells, or MDSCs, which help tumors to stay hidden from the T-cells dispatched by the body’s immune system. Sildenafil seems to disable the elaborate protective system of the MDSCs so that the immune system can more readily identify tumor cells and eradicate them.
In a small-scale human study, Johns Hopkins researchers built on what they had learned from the 2006 study. In the human study, a 50-year-old patient with end-stage multiple myeloma was treated with tadalafil, better known by its Cialis brand name and yet another of the impotence drugs in the PDE5 inhibitor family. Tadalafil worked very much the same way as sildenafil had in animal studies, blocking MDSC function and restoring the patient’s immune responsiveness.
Still Other Applications
Already marketed under the brand name of Revatio as a treatment for pulmonary arterial hypertension, sildenafil has also been shown to be helpful in treating a number of other ailments. In a recently published study, Chinese researchers at Wenzhou Medical University found that sildenafil significantly reduced symptoms in women with interstitial cystitis, a chronic bladder condition. In a double-blind, placebo-controlled study of 54 women with IC, sildenafil achieved an overall effectiveness rate of 62.5 percent.
In a recently published review of 24 studies in which men with a history of cardiovascular disease took sildenafil, Italian researchers found a good deal of evidence that the impotence drug can be helpful in treating heart disease. Specifically, the review found that sildenafil was particularly useful in treating early-stage heart failure and in preventing a thickening of the heart muscle, which negatively affects cardiac function.
Don Amerman is a freelance author who writes extensively about a wide array of nutrition and health-related topics.
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