Tag: oxidative stress

Categories : CancerTags :

Oxidative Stress Contributes to Multi-drug Resistance in Chemotherapy

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Shown here is a pseudo-colored scanning electron micrograph of an oral squamous cancer cell (white) being attacked by two cytotoxic T cells (red), part of a natural immune response. Photo by National Cancer Institute on Unsplash

Researchers have found that oxidative stress plays a role the inevitable occurrence of multi-drug resistance during tumour therapy, which they report in the Journal of Biochemical and Molecular Toxicology. 

While chemotherapy is a mainstay of cancer treatment, it is often hindered by the development of drug resistance, eventually evolving into multidrug-resistance which renders most drugs ineffective. 

Multidrug resistance is responsible for over 90% of deaths in cancer patients receiving traditional chemotherapeutics or novel targeted drugs. Its mechanisms include elevated metabolism of xenobiotics, enhanced efflux of drugs, growth factors, increased DNA repair capacity, and genetic factors (gene mutations, amplifications, and epigenetic alterations).

The most well-known mechanism is the induction of Adenosinetriphosphate (ATP)-binding cassette (ABC) transporters by chemotherapeutic drugs. These transporters are highly expressed in cancer cells and pumped out chemotherapeutics to make the treatment ineffective. 

Earlier research had shown that non-substrate nanoparticles could induce multidrug resistance by inducing oxidative damage, suggesting that multidrug resistance could be induced by oxidative damage as well as the substrate. 

To confirm the this, Yin Jian and his team investigated the interaction of three chemical agents (ethanol, hydrogen peroxide, and doxorubicin) with ABC transporters using a lung cancer cell line (A549) as a model. 

Among the three chemicals, doxorubicin is the substrate of ABC transporter and chemotherapeutic drugs, while ethanol and hydrogen peroxide are small-molecule compounds, which have no relationship with the function of ABC transporter. 

“When the three substances enter the cells, they can cause significant oxidative stress inside cells,” said Yin.  

The elevated oxidative stress induced the expression of transporters, and the elevated transporters reduce intracellular oxidative stress by effluxing oxidized glutathione. In this process, pregnane X receptor played an important regulatory role. 

Their results suggested that non-substrate chemicals could also induce ABC transporter expressions similar to chemotherapeutic agents after inducing oxidative damage. This phenomenon could be regarded as a non-specific feedback of tumor cells/ABC transporters to external stimuli. 

The conclusions validated the relationship between multidrug resistance mechanisms and oxidative stress. This would help to design advanced strategies on how to enhance this mechanism to more effectively combat ABC transporter-mediated multidrug resistance.  

“Considering that peroxidative damage is the main source of the toxicity of current environmental pollutants, long-term exposure to environmental pollutants could not only induce direct toxicity, but also further threaten human health by inducing multi-drug resistance,” said Yin Huancai, another researcher from the team. 

Source: China Academy of Sciences

Categories : LungTags :

Vaping Raises Oxidative Stress Levels Even in Nonsmokers

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Photo by Toan Nguyen on Unsplash
Photo by Toan Nguyen on Unsplash

In addition to the well-documented risks of smoking and vaping, a new UCLA study has revealed that a short vaping session can affect the cells of even healthy younger nonsmokers.

According to their study, published in JAMA Pediatrics, a single 30-minute vaping session can significantly increase cellular oxidative stress, which occurs when the body has an imbalance between free radicals, and the antioxidants which neutralise them.

“Over time, this imbalance can play a significant role in causing certain illnesses, including cardiovascular, pulmonary and neurological diseases, as well as cancer,” said the study’s senior author, Dr Holly Middlekauff, a professor of cardiology and physiology at the David Geffen School of Medicine at UCLA.

E-cigarettes, devices that deliver nicotine with flavouring and other chemicals in a vapour rather than smoke, are popularly seen as a safer cigarette alternative, but research by Prof Middlekauff and others has demonstrated that vaping is associated with a number of adverse changes in the body that can presage future health problems.

For the present study, 32 male and female study participants, aged 21 to 33, were split into three groups: 11 nonsmokers, nine regular tobacco cigarette smokers and 12 regular e-cigarette smokers. The researchers collected immune cells from each individual before and after a 30-minute vaping session to measure and compare changes in oxidative stress among the groups.

The researchers repeated this with a control session where participants spent 30 minutes “sham-vaping,” or puffing on an empty straw.

In nonsmokers, oxidative stress levels were found to be two to four times higher after the vaping session than before. Among the regular cigarette and e-cigarette smokers, the same 30-minute exposure did not lead to an increase in oxidative stress, the researchers noted, most likely because their baseline levels of oxidative stress were already increased.
“We were surprised by the gravity of the effect that one vaping session can have on healthy young people,” Prof Middlekauff said. “This brief vaping session was not dissimilar to what they may experience at a party, yet the effects were dramatic.”

The researchers noted that these results are especially troubling due to the increasing popularity of vaping, particularly among the youth. In a 2020 study, nearly a third of high school students reported e-cigarette use during the previous month.

There is still more to be understood about what exactly causes the changes in oxidative stress levels, whether it is caused by the nicotine or non-nicotine elements in e-cigarettes, which will be the subject of future research.

“While there’s a perception that e-cigarettes are safer than tobacco cigarettes, these findings show clearly and definitively that there is no safe level of vaping,” Prof Middlekauff said. “The results are clear, unambiguous and concerning.”

Source: UCLA