Reactive oxygen species

Roundup Toxicity May Impact Male Fertility: Study

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In 2011, Purdue University professor emeritus Don Huber notified US Agriculture Secretary Tom Vilsack, with a letter warning that tests show glyphosate, the active ingredient in Monsanto’s Roundup herbicide, may be contributing to spontaneous abortions and infertility in pigs, cattle, and other livestock.

This wasn’t the first time the chemical had been implicated as a threat to fertility, nor was it the last. Steep declines in human male sperm counts have been occurring alongside rises in birth defects of the male reproductive tract, and now new research suggests increasing exposure to glyphosate and Roundup may be at least partially to blame.

Male Fertility

Story at-a-glance –

  • Research is mounting that an environmental toxicant, especially an endocrine-disrupting chemical such as glyphosate in Roundup, may be involved in increasing rates of male infertility
  • Roundup exposure induced cell death in Sertoli cells (required for male sexual development and sperm health) in rat testis
  • The exposure was a low dose (36 parts per million), which is well within the US Environmental Protection Agency’s food safety exposure levels
  • Separate research showed that glyphosate led to severe oxidative stress in male testes, which leads to the generation of reactive oxygen species (ROS); ROS is linked to male infertility

There’s No Denying Trends in Infertility and Poor Semen Quality

A new report from the Institute of Science in Society (ISIS) has highlighted what appears to be the perfect storm for an “infertility time-bomb,” courtesy of Roundup.1 Average sperm counts have dropped by nearly half in the last 50 years, even among men without fertility problems.

Further, ISIS noted, 20 percent of young European men have sperm counts below the World Health Organization (WHO) reference level of 20 m/ml, and 40 percent have levels below 40 m/ml, which is associated with prolonging the time to pregnancy. Meanwhile, rates of conditions that impact semen quality and fertility are also on the rise. ISIS noted the following, in particular:

“Testicular germ cell cancer (TGC), which has been rising in the last five decades. Congenital malformations of the male reproductive tract, including undescended testes and incomplete fusion of the urethral folds that form the penis. Low testosterone.”

There are, of course, many potential explanations for these conditions, but, as ISIS noted, it has been proposed that an environmental toxicant, especially an endocrine-disrupting chemical such as glyphosate, may be involved. ISIS explained:

“In Europe, incidences of TGC and congenital reproductive tract malformations have been going up coincidentally with a downward trend in semen quality and testosterone levels…

These disorders share common risk factors and are risk factors for one another. Consequently, it has been proposed that the conditions collectively may represent a syndrome — a testicular dysgenesis syndrome (TDS) — caused by a common underlying causal factor, which is either a change in lifestyle or an environmental toxin, especially endocrine disrupting chemicals such as pesticides.”

Roundup Linked to Male Infertility Even at Low Doses

Of particular concern is a study published in December 2013, which revealed that Roundup exposure induced cell death in Sertoli cells in prepubertal rat testis.2 Sertoli cells are required for male sexual development, including maintaining the health of sperm cells.

The exposure was a low dose (36 parts per million), which is well within the US Environmental Protection Agency’s food safety levels.3 After 30 minutes of exposure, researchers found that Roundup yielded several disruptions to the cells’ health, including:

  • Induced oxidative stress
  • Activated multiple stress-response pathways
  • Increased intracellular calcium concentration, leading to calcium overload and cell death

The researchers proposed:

“Roundup toxicity, implicated in Ca(2+) [calcium] overload, cell signaling misregulation, stress response of the endoplasmic reticulum, and/or depleted antioxidant defenses, could contribute to Sertoli cell disruption in spermatogenesis that could have an impact on male fertility.”

It’s the latest in a series of studies that have pointed toward Roundup’s troubling impacts on fertility and reproductive health. Other studies have similarly found:4

  • Prepubertal exposure to glyphosate alters testosterone levels and is a potent endocrine disruptor5
  • Exposure to concentrations as low as 1 part per million (ppm) of Roundup and glyphosate decreased testosterone in rat sperm cells by 35 percent6
  • Exposure to Roundup may alter the structure of the testis in ducks, leading researchers to conclude the herbicide may “cause disorder in the morphophysiology of the male genital system of animals”7

Is Roundup-Induced Oxidative Stress Harming Sperm?

A separate study published last year further showed that glyphosate (in combination with another pesticide) led to severe oxidative stress in male testes.8 This may be a key reason for Roundup’s endocrine-disrupting effects, as oxidative stress leads to the generation of reactive oxygen species (ROS). ROS are known to induce DNA damage and decrease sperm counts, linking them closely with male infertility. As ISIS reported:

“ROS is so closely linked to male infertility that infertile males generating high levels of ROS are 7 times less likely to initiate a pregnancy compared with those with low levels of ROS. A meta-analysis demonstrated that ROS levels were significantly correlated with the fertilization rate in couples undergoing in vitro fertilization. …[Researchers have] concluded that high ROS is an independent marker of MFI [male factor infertility], irrespective of whether these patients have normal or abnormal semen parameters.”

Roundup May Be Even More Toxic Than Glyphosate

While glyphosate is often blamed for much of Roundup’s toxicity, Roundup is a glyphosate-based pesticide with adjuvants. These adjuvants, it turns out, may be toxic in their own right, as well as may act synergistically with glyphosate to greatly heighten its damaging effects.

POEA (polyethoxylated tallowamine), a major adjuvant surfactant in Roundup, has been shown to be cytotoxic (toxic to cells) at doses far lower than glyphosate itself. Unfortunately, most regulatory bodies regard POEA as inert, requiring no risk assessment, even as research suggests otherwise. ISIS reported:

“The major adjuvant POEA in glyphosate Roundup formulations is by far the most cytotoxic for human cells, ahead of glyphosate and its metabolite. It also amplifies the toxic effects of glyphosate…

It is very likely that the primary target of Roundup, especially its POEA surfactant, is the mitochondria, which play a key role in the development of sperm cells and sperm motility. In addition, male infertility could arise from ROS damages to mitochondrial DNA.”

Glyphosate May Contribute to Numerous Chronic Diseases

Glyphosate has a number of devastating biological effects, so much so that it may very well be one of the most important factors in the development of a wide variety of modern diseases and conditions. According to a peer-reviewed report9 authored by Anthony Samsel, a retired science consultant, and Dr. Stephanie Seneff, a research scientist at the Massachusetts Institute of Technology (MIT), these detrimental effects include:

Nutritional deficiencies, as glyphosate immobilizes certain nutrients and alters the nutritional composition of the treated crop Disruption of the biosynthesis of aromatic amino acids (these are essential amino acids not produced in your body that must be supplied via your diet)
Increased toxin exposure (this includes high levels of glyphosate and formaldehyde in the food itself) Impairment of sulfate transport and sulfur metabolism; sulfate deficiency
Systemic toxicity—a side effect of extreme disruption of microbial function throughout your body; beneficial microbes in particular, allowing for overgrowth of pathogens Gut dysbiosis (imbalances in gut bacteria, inflammation, leaky gut, and food allergies such as gluten intolerance)
Enhancement of damaging effects of other food-borne chemical residues and environmental toxins as a result of glyphosate shutting down the function of detoxifying enzymes Creation of ammonia (a byproduct created when certain microbes break down glyphosate), which can lead to brain inflammation associated with autism and Alzheimer’s disease

REMEMBER — If You Eat Processed Foods, You’re Eating Glyphosate

You’d be wise to stop using Roundup around your home, where children and pets can come into contact with it simply by walking across the area. However, this is only the tip of the iceberg when it comes to Roundup (and glyphosate) exposure. It’s important to understand that the glyphosate sprayed on conventional and genetically modified (GM) crops actually become systemic throughout the plant, so it cannot be washed off. It’s inside the plant. For example, genetically engineered corn has been found to contain 13 ppm of glyphosate compared to zero in non-GMO corn. Organ damage in animals has occurred at levels as low as 0.1 ppm or 130 times the “safe” human EPA limit.

The vast majority of processed foods sold in the US are made with GM corn and soy ingredients. So if you consume such foods, you should know you’re also consuming glyphosate. Tests show that people in 18 countries across Europe already have glyphosate in their bodies.10 The answer, of course, is to avoid processed foods of all kinds, as they’re virtually guaranteed to contain GM ingredients, and center your diet around whole, organic foods, as toxic pesticides (and GM ingredients) are not permitted in organic farming.

Vote with Your Pocketbook, Every Day

The food companies on the left of this graphic spent tens of millions of dollars in the last two labeling campaigns—in California and Washington State—to prevent you from knowing what’s in your food. You can even the score by switching to the brands on the right, all of whom stood behind the I-522 Right to Know campaign. Voting with your pocketbook, at every meal, matters. It makes a huge difference.

As always, I encourage you to continue educating yourself about genetically modified foods, and to share what you’ve learned with family and friends. Remember, unless a food is certified organic, you can assume it contains GMO ingredients if it contains sugar from sugar beet, soy, or corn, or any of their derivatives.

If you buy processed food, opt for products bearing the USDA 100% Organic label, as organics do not permit GMOs. You can also print out and use the Non-GMO Shopping Guide, created by the Institute for Responsible Technology. Share it with your friends and family, and post it to your social networks. Alternatively, download their free iPhone application, available in the iTunes store. You can find it by searching for ShopNoGMO in the applications. For more in-depth information, I highly recommend reading the following two books, authored by Jeffrey Smith, the executive director of the Institute for Responsible Technology:

  • Seeds of Deception: Exposing Industry and Government Lies about the Safety of the Genetically Engineered Foods You’re Eating
  • Genetic Roulette: The Documented Health Risks of Genetically Engineered Foods.

For timely updates, join the Non-GMO Project on Facebook, or follow them on Twitter. Please, do your homework. Together, we have the power to stop the chemical technology industry from destroying our food supply, the future of our children, and the earth as a whole. All we need is about 5 percent of American shoppers to simply stop buying genetically engineered foods, and the food industry would have to reconsider their source of ingredients—regardless of whether the products bear an actual GMO label or not.

Arsenic trioxide plus PX-478 achieves effective treatment in pancreatic ductal adenocarcinoma

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Highlights

  • •ATO plus PX-478 (HIF-1 inhibitor) controls PDAC by ROS accumulation.
  • •HIF-1 directly activates the transcription of FOXO1 in PDAC.
  • •HIF-1 removes intracellular ROS by the FOXO1/SESN3 pathway.

Abstract

Arsenic trioxide (ATO) has been selected as a promising treatment not only in leukemia but also in solid tumors. Previous studies showed that the cytotoxicity of ATO mainly depends on the induction of reactive oxygen species. However, ATO has only achieved a modest effect in pancreatic ductal adenocarcinoma, suggesting that the existing radical scavenging proteins, such as hypoxia inducible factor-1, attenuate the effect. The goal of this study is to investigate the effect of combination treatment of ATO plus PX-478 (hypoxia-inducible factor-1 inhibitor) and its underlying mechanism. Here, we showed that PX-478 robustly strengthened the anti-growth and pro-apoptosis effect of ATO on Panc-1 and BxPC-3 pancreatic cancer cells in vitro. Meanwhile, in vivo mouse xenograft models also showed the synergistic effect of ATO plus PX-478 compared with any single agent. Further studies showed that the anti-tumor effect of ATO plus PX-478 was derived from the reactive oxygen species-induced apoptosis. We next confirmed that Hypoxia-inducible factor-1 cleared reactive oxygen species by its downstream target, forkhead box O transcription factors, and this effect may justify the strategy of ATO plus PX-478 in the treatment of pancreatic cancer.

Researchers film early concussion damage, describe brain’s response to injury.

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There is more than meets the eye following even a mild traumatic brain injury. While the brain may appear to be intact, new findings reported in Nature suggest that the brain’s protective coverings may feel the brunt of the impact.

Using a newly developed mouse trauma model, senior author Dorian McGavern, Ph.D., scientist at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, watched specific cells mount an  to the injury and try to prevent more widespread damage. Notably, additional findings suggest a similar immune response may occur in patients with mild head injury.

In this study, researchers also discovered that certain molecules, when applied directly to the mouse skull, can bypass the brain’s protective barriers and enter the brain. The findings suggested that, in the mouse trauma model, one of those molecules may reduce effects of .

Although concussions are common, not much is known about the effects of this type of damage. As part of this study, Lawrence Latour, Ph.D., a scientist from NINDS and the Center for Neuroscience and Regenerative Medicine, examined individuals who had recently suffered a concussion but whose initial scans did not reveal any physical damage to brain tissue. After administering a commonly used dye during MRI scans, Latour and his colleagues saw it leaking into the meninges, the outer covers of the brain, in 49 percent of 142 patients with concussion.

To determine what happens following this mild type of injury, researchers in Dr. McGavern’s lab developed a new model of brain trauma in mice.

“In our mice, there was leakage from blood vessels right underneath the skull bone at the site of injury, similar to the type of effect we saw in almost half of our patients who had mild . We are using this mouse model to look at meningeal trauma and how that spreads more deeply into the brain over time,” said Dr. McGavern.

Dr. McGavern and his colleagues also discovered that the intact skull bone was porous enough to allow small molecules to get through to the brain. They showed that smaller molecules reached the brain faster and to a greater extent than larger ones. “It was surprising to discover that all these protective barriers the brain has may not be concrete. You can get something to pass through them,” said Dr. McGavern.

The researchers found that applying glutathione (an antioxidant that is normally found in our cells) directly on the skull surface after brain injury reduced the amount of  by 67 percent. When the researchers applied glutathione three hours after injury, cell death was reduced by 51 percent. “This idea that we have a time window within which to work, potentially up to three hours, is exciting and may be clinically important,” said Dr. McGavern.

Glutathione works by decreasing levels of reactive oxygen species (ROS) molecules that damage cells. In this study, high levels of ROS were observed at the trauma site right after the physical brain injury occurred. The massive flood of ROS set up a sequence of events that led to cell death in the brain, but glutathione was able to prevent many of those effects.

In addition, using a powerful microscopic technique, the researchers filmed what was happening just beneath the skull surface within five minutes of injury. They captured never-before-seen details of how the brain responds to traumatic injury and how it mobilizes to defend itself.

Initially, they saw cell death in the meninges and at the glial limitans (a very thin barrier at the surface of the brain that is the last line of defense against dangerous molecules). Cell death in the underlying brain tissue did not occur until 9-12 hours after injury. “You have death in the lining first and then this penetrates into the brain tissue later. The goal of therapies for brain injury is to protect the ,” said Dr. McGavern.

Almost immediately after head injury, the glial limitans can break down and develop holes, providing a way for potentially harmful molecules to get into the brain. The researchers observed microglia (immune cells that act as first responders in the brain against dangerous substances) quickly moving up to the brain surface, plugging up the holes.

Findings from Dr. McGavern’s lab indicate that microglia do this in two ways. According to Dr. McGavern, “If the astrocytes, the cells that make up the glial limitans, are still there, microglia will come up to ‘caulk’ the barrier and plug up gaps between individual astrocytes. If an astrocyte dies, that results in a larger space in the glial limitans, so the microglia will change shape, expand into a fat jellyfish-like structure and try to plug up that hole. These reactions, which have never been seen before in living brains, help secure the barrier and prevent toxic substances from getting into the brain.”

Studies have suggested that immune responses in the brain can often lead to severe damage. Remarkably, the findings in this study show that the inflammatory response in a model is actually beneficial during the first 9-12 hours after injury.

Mild traumatic brain injuries are a growing public health concern. According to a report from the Centers of Disease Control and Prevention, in 2009 at least 2.4 million people suffered a traumatic injury and 75 percent of those injuries were mild. This study provides insight into the damage that occurs following head trauma and identifies potential therapeutic targets, such as antioxidants, for reducing the damaging effects.