Poison by Any Other Name

Apr 05 2012 Published by under [Medicine&Pharma]

Evil chemicals! Click for source

What image springs to mind when you see the word...

nicotine?

If you smoke, you may have a warm, fuzzy feeling, but for a lot of us, poison comes to mind. Nicotine makes tobacco products addictive, so it cannot be good. See the diagram at right; it's used as an insecticide! It kills bugs! It must be bad!

Of course, nicotine is merely a chemical. But chemicals are bad, right? Even a natural one that comes from a plant (like tobacco)? Even one with a short, pronounceable name?

So nicotine is bad...except when it isn't.

Renoprotective effects of long-term oral nicotine in a rat model of spontaneous proteinuria.
Agarwal et al. Am J Physiol Renal Physiol 302:F895, 2012
DOI:  10.1152/ajprenal.00507.2011

Nicotine has demonstrated beneficial effects in a number of inflammatory disorders, including inflammatory bowel disease, sepsis, and hypersensitivity pneumonitis. In animal models of ischemia-reperfusion kidney injury results are more variable, depending on the model and route of nicotine administration. It seems that macrophages (immune white blood cells) and capillaries in the kidney have alpha-7 nicotinic acetylcholine receptors which modulate these anti-inflammatory effects.

This study used a rat model of spontaneous proteinuria, Munich-Wistar-Fromter rats. As these rats age, they develop proteinuria. As protein is reabsorbed by the peritubular capillaries in the kidney, filtered agents such as cytokines and growth factors can promote inflammation and further kidney damage. At the time proteinuria begins in this model (24 weeks, a middle-aged rat), animals were begun on one of three doses of nicotine in drinking water along with an untreated control group. Saccharine in the water in all groups masked the taste of nicotine (yes, the control rats were drinking diet soda, circa 1970). Every 4 weeks they measured blood pressure, glomerular filtration rate, and proteinuria. They examined kidney structure in a number of ways after 28 weeks of study, when the rats reached one year of age.

Kidney function (upper panel) & proteinuria (lower panel)

The control rats showed the typical course for the MWF model, with glomerular filtration rates less than half of baseline after 28 weeks of study (see figure at left). This effect on clearance of waste products was blunted by nicotine ingestion. Protein excretion increased in all groups of rats, but, once again, nicotine treatment reduced the level of protein spill.

Nicotine treatment also reduced scarring in the glomeruli, the filtering units of the kidneys. Macrophages, those pesky blood cells that promote inflammation and scarring, were also reduced by nicotine treatment. Production of scar materials by the kidney was also reduced with the nicotine treatment.

So proteinuric patients should smoke? Or at least wear those patches?

Not exactly.

Smoking is a major risk factor for the development and progression of all sorts of kidney diseases. We ABSOLUTELY DO NOT WANT ANYONE SMOKING EVER FOR ANY REASON!

Like most molecules, nicotine has many faces. In this case, we examined its perky, anti-inflammatory side. Nicotine also has other effects that may not be desirable. Short-term ingestion raises blood pressure and heart rate via stimulation of the adrenergic system; these effects were not detected with long-term ingestion in this rat model. Nicotine also affects a number of systems that modulate blood flow (and can therefore affect function) of the kidney. Changes in these systems were not assessed in the present study.

Also, prior studies show that what happens in rats does not necessarily happen in mice when it comes to nicotine. Why? We really do not know. Do these species metabolize nicotine differently? Or is there some other reason for these differences? When it comes to nicotine, are people more like rats or mice or neither?

Nicotine has another danger: addiction. Can we come up with a modified nicotine (with a longer, scarier, more chemically name) that would provide anti-inflammatory effects without producing undesirable vascular or behavioral effects? Anything is possible, but this molecule is still in the future.

The bottom line: nicotine from a natural, plant-based source like tobacco can be a killer. Pure nicotine from the lab may be a healer. Only time and more experiments will tell.

2 responses so far

  • drugmonkey says:

    Nicotine is also a decent cognitive enhancer. It's just the delivery system is such an asshole. Plus, like you said, addiction.

  • Crystal Voodoo says:

    I will preface this statement with the admission that I am entirely biased on this topic. Tobacco is not the only method to administer nicotine. Electronic cigarette technology administers nicotine in vapor form using propylene glycol or vegetable glycerin as a carrier molecule spiked with a flavoring. Clearly the long term health effects haven't been adequately tested but I appreciate not wheezing when going upstairs and the cost is pennies compared to tobacco. The downside is that my overall consumption has increased significantly in the conversion. I just thought I might put this out there.

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