Effects of lead on the liver: Hepatotoxicity

Although it has been widely known that lead can enter through the gastrointestinal tract, we (the writers of this blog) have focused on lead’s effects on the immune system, the brain and development, blood pressure, or on humans and animals as a whole. However, if lead was poisonous to the entire body, then some part of the GI tract would be affected as well through ingestion of lead. Which part of the GI tract would be hit the hardest? Most likely, the organ that has to filter the excess lead out of the blood stream after it is ingested and absorbed: the liver.

The article ‘Lead hepatotoxicity & potential health effects’ by Mudipalli is an overview on the liver problems and diseases that can be caused by exposure to lead. According to the article, primary exposure is through either the respiratory or GI systems, and the absorbed lead is stored mostly in soft tissue and bone. Besides the neurotoxic effects of heavy lead exposure, gastrointestinal colic, which has symptoms of abdominal pain, constipation, and intestinal paralysis, is a consistent early sign of lead exposure. The liver is the first organ to be exposed to absorbed nutrients, because of the portal vein. Lead can cause parts of the liver to become cancerous, or fail in some of its functions, such as drug and cholesterol metabolism. Since the liver is connected to the GI tract, most hepatoxic effects are caused by ingestion, instead of respiration, of lead.

The article goes into detail on the individual mechanisms that damage liver function, such as the reduction in activity of cytochrome p50 (CYP50), which is a major part of drug metabolism. It also discusses some basic studies done to people who are at a higher risk of lead exposure, such as factory workers, gas station attendants, and construction workers. In short, an increased serum lead concentration caused a decrease in CYP50 metabolite excretion. Also, increased levels of lead induce one of the enzymes essential for cholesterol synthesis. The article continues on by detailing the mechanism behind lead’s effect of decreased heme synthesis, hepatic hyperplasia, and increased oxidative stress. It finishes on a positive note, discussing the lead-chelating methods that are therapeutic to lead-induced hepatic toxicity.

This article is very conducive to the rest of the articles posted. While the effects may not seem to be as critical as some of the other organs/systems that were discussed, they still impair liver function, which is dangerous to the entire body. If the liver cannot metabolize drugs on the regular pace, then the threshold of toxic-doses would be lower from everything from drugs like acetaminophen and alcohol to vitamins, like vitamin A and D.

The link to the article can be found here:

http://www.icmr.nic.in/ijmr/2007/december/1205.pdf

Lead Levels in Paint

(Hey everyone, here is a highly publicized issue in relation to lead toxicity. Lead in paint) 

This journal article, titled ‘Lead levels in new enamel household paints from Asia, Africa and South America’ by Clark et al, deals with levels of lead in newly produced paints from twelve different countries in Africa, Asia and South America. The researchers who conducted the study took three hundred and thirty seven samples from paints produced in twelve different countries. They took these samples from paints that were available in public paint shops and the paint was extracted from the surface it was applied on and analyzed using absorption spectroscopy. The results of the study show that the overall lowest average for lead concentration, around 6988ppm, in paints came from Singapore while the highest average lead concentration, around 31,960 ppm, was present in the paints that were produced in Ecuador. Also, the data shows that the lowest average lead concentration were present in white paint, around 1547 ppm, while the highest average levels of lead poisoning were present in yellow paint which had a level around 47,250 ppm. It has also been found that the darker less vibrant hues, such as white, brown, black and blue, had levels of lead that were found to be les than the mandated cut off level of lead which is 600ppm. The white paint was found to have the lowest percentage, around 33%, of samples in which the cutoff was exceeded or equaled. In comparison, for the orange paints around 89% of the samples exceeded or equaled the cutoff levels. Furthermore, it was discovered that fifty four percent of the paints produced in Singapore and China had concentrations less than the United States’ cutoff level for lead concentration in paints of 90ppm. From these findings the researchers were able to conclude that the technology necessary to produce low lead level paints is currently available (Clark et al.., 2009).

The issue of high lead concentration in paint and controlling levels of harmful lead has been a pivotal one in terms of toxic substances. This is so because children who are easily affected by lead are readily exposed to it in whenever they are in older homes which were painted using high lead concentrated paint. Also, another avenue for lead to enter the bodily systems of children is through toys, which were also painted using paint that contained high levels of lead. Recently, the United States has emphasized its policy on low lead levels by reducing the mandatory cutoff level of lead in paint to 90 ppm. The emphasis on lead and reducing concentrations of it paint and other sources are due to its menagerie of toxic effects that are especially magnified in children whose bodies are developing and thus, absorb more lead than adults. These effects in children include, brain and nervous system damage leading to subsequent behavior and learning problems, hearing problems, slowed development and maturity. In adults, these effects include reproductive issues, high blood pressure and hypertension, muscle and joint pains and memory and concentration problems (Epa.gov, 2009). I believe that the Unites States is making great progress in terms of reducing lead contamination and exposure through new regulates. I was especially overjoyed to see the recall of two million toys that did not meet the new standards of lead paint concentration. 

The Links to the article and Website used are as follows:

1. http://www.mediafire.com/file/z3zoomkdzow/Leadlevels.pdf
2. http://www.epa.gov/lead/pubs/leadinfo.htm#health

China faces reckoning over lead production

As we have mentioned in this blog, lead poisoning is a major problem in different areas of the world, especially in developing nations. This problem is becoming a big problem in China. In Jiyuan, China, where a large amount of car battery factories are located, villages are being evacuated due to lead poisoning. Of these people being evacuated, the children are in the worst health due to the fact that lead demonstrates a stronger toxic effect in children. Some of the children have blood levels of lead that reach 355 micrograms per liter (anything over 100 is dangerous). The inhabitants of the town commented that the children are shrinking away. Even the older inhabitants are experiencing mental problems like loss of short-term memory. The heavy amount of pollution in this province not only has poisoned the inhabitants but has also presented some social problems. Resident Han Haibo stated, "People don't want to leave, especially the old people who have spent their whole lives here, but the pollution is just too heavy."

China is the largest producer and consumer of lead. It also has some of the highest pollution levels in the world. The residents of Jiyuan also mentioned that looking at the landscape is like looking out of a dirty windshield. Due to the production of electrolytic lead for car batteries, there is a fine dust of metal in the air. The main reason why everyone in this area is becoming ill is due to the fact that the children play in that polluted environment and the whole area eats food grown from that polluted land. The worst piece of information in this whole story is that the residents of this area allowed the car battery companies to build their factories in that location. This decision was made mainly due to the lucrative jobs and lifestyles the car battery companies could provide for their families. For the time being, I believe that the inhabitants of this area need to vacate and find another residence despite the economic effects. Health is the most valuable asset any of these people can have and without that life is meaningless.

http://www.latimes.com/news/nationworld/nation/la-fg-china-lead14-2009nov14,0,963625.story

Sex-Specific Effects of Lead Toxicity in Infants

The journal article ‘Children’s Health: Sex-Specific Cognitive Effects of Lead’ by Barrett looked at the neurotoxic effects of lead in infant children and wanted to determine if there was any difference between male and female infants in terms of neurotoxicity. Lead is extremely harmful to the developing brain, and early exposure can limit children’s cognitive and behavioral development. The original threshold was at 10ug/dL, but other research states that the number may be actually lower.

The study used 457 infants following certain criteria, such as the mothers being non-smokers and not having a history for chronic diseases like hypertension and diabetes. When the infants were born, a cord blood sample was collected to determine lead concentration. At 12, 24, and 36 months, the Mental Development Index (MDI) of the Bayley Scales of Infant, which is a common tool used to assess the mental development of young children. Normal MDI scores are at least 85; below 85 indicates delayed development. Amongst boys, a higher cord blood lead level was significantly associated with a 4.5 point drop in MDI scores. Herbert Needleman, one of the researchers, states that boys are more sensitive to all brain insults, including neurotoxic agents and head injuries. According to him, the ‘basic’ brain is female, and masculinity is an addition, and therefore it is more easily damaged.

I think this article is critical for future research and overall concern for pregnant mothers in terms of lead toxicity. It enforces the general idea that anything that is toxic to the human body is toxic at lower concentrations in the unborn fetus, and therefore pregnant mothers should avoid lead-based items as much as possible during their pregnancy, in a similar fashion to cigarettes, alcohol, and other toxic substances.

The full article can be found here:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737040/?tool=pubmed

Developmental Exposure of Lead Toxicity in Pregnant Mice

In this study, nine-week-old pregnant female rats were exposed to various concentrations of lead acetate while in their breeding and pregnancy stage via water intake. These young offspring from the female rats were not exposed to any other lead concentrations after the initial introduction to their mothers. Several tests were used to detect any significant changes in immunotoxicity when offspring are 13 weeks in age. Results showed that macrophage cytokine functions, which include NO2 production and tumor necrosis factor-alpha) were increased in the 250 ppm group. In this same group, cell-mediate immunity showed decreased levels. There were also higher levels of serum IgE in offspring of rats that received 100ppm. What’s surprising in this study is that the mothers that were initially given the lead acetate showed no chronic immune changes or physiological changes while the embryos showed significant detectable immunotoxicity levels, which further substantiates the hypothesis that lead exposure has higher immune sensitivity levels (specifically changing the balance between type 1 and type 2 responses) in embryos compared to that of adults.

This study was significant in its contribution to demonstrating how lead exposure in rats can cause immunomodulatory effects on offspring during development. This study can be comparable to the human model because some studies of lead toxicity in children have reported slightly lower blood lead concentrations than in mice that are reported to affect behavioral function. The most important finding is that offspring blood and bone of measured lead levels during the immune analysis were surprisingly low, which indicates that pregnant females and other species including humans, can pass defective immune function with even short-term exposure to lead.

Miller, T.E., Golemboski, K.A., Ha, R.S., Bunn, T., Sanders, F.S., Dietert, R.R. (1998) Developmental exposure to lead cause persistent immunotoxicity in Fischer 344 rats. Toxicology Science. 42(2): 129-35.

Current concerns of Lead Toxicity

This article presents an overview of lead toxicity and a number of public concerns. It has been discovered that 10-15 micrograms/dL of lead in the bloodstream of newborns and infants can result in cognitive defects. At this blood stream concentration of lead, newborns and infants experience a reduction of 4-7 IQ points. These effects on newborns and infants are dose-dependent so the higher the lead exposure, the higher the reduction in IQ observed.

Lead has also been discovered to disrupt the central nervous system. The reason lead causes this problems are due to lead’s interactions with calcium mediated intracellular messenger systems and neurotransmission. These effects have been more readily observed in developing brains due to the higher susceptibility of immature endothelial cells to the negative effects of lead.

Low-level exposure to lead has also been discovered to raise blood pressure in adults. Researchers did not initially observe this effect due to the fact that a change in blood pressure is not really observed in high amounts of exposure to lead. The exposure to small amounts of lead (2-15 ug/dL in the bloodstream) leads to systolic pressures that vary from 102 to 173 mmHg and diastolic pressures from 61 to 105 mmHg.

Adverse health defects caused by lead exposure are preventable. The major factors of lead toxicity are age, nutrition, and housing and socioeconomic status. Younger children have been discovered to be at increased risk of lead toxicity due to their high lead intake according to their body size and greater absorption of lead through their gastrointestinal tract. Lead has been detected in water, beverages, and food. An initiative has started in the US to reduce the lead exposure through nutrition. The last major factor in lead exposure is housing and socioeconomic status. The housing of people with lower socioeconomic status has a high tendency to have lead paint and contain toxic materials. This invariably increases this section of the population’s exposure to lead and is a major reason why their bloodstream lead concentrations are elevated.

The article can be found here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1519587/

Speciation of Cd and Pb in dust emitted from sinter plant

(Hey Everyone, here is a journal about lead inhalation and how particles of lead reach our lungs...) 

(A sinter plant from 1939)

This journal article,' Speciation of Cd and Pb in dust emitted from sinter plant' by Sammut et al,   examines the speciation of the heavy metals lead and cadmium in steel dust spewn from sinter plants. It states the fact that the toxicity of heavy metals depends primarily upon speciation, which is the quantity of a particular substance of interest in an entity. In this case the researchers discovered that the lead is found to be complexed with carbonate and the cadmium with chloride. This was discovered through the usage of an array of tests ranging from "XRF, EXAFS or ICP-AES and chemical leaching". This association of the heavy metals is particularly toxic simply due to the fact that chloride and carbonate are highly soluble at normal environmental constraints (Sammut et al.., 2009). 

This would potentially allow for the metals to enter the ecosystem, eventually reaching humans. Also, the noxious dust particles could be inhaled by humans. This is harmful as inhaled lead becomes trapped in the lungs and enters the bloodstream. Once absorbed in to the blood lead is capable of disrupting normal enzyme synthesis and activity as it binds to the sulfhydryl groups present within enzymes. It also mimics the various cofactors utilized by enzymes. One particular enzyme pathway lead interferes with considerably is the synthesis of heme. 

I think that industrial plants such as sinter plants and smelting plants should either be shut down or closely regulated. The sheer quantity of lead and other toxic substances released by these plants is incredible and their toxic effects are evidenced by populations residing near these plants. Closing down these plants or cleaning up their emissions would profoundly alter lead levels in the air as well as reduce air pollution. 

The full Journal article can be found here:

http://www.mediafire.com/file/cbkjhzhzety/Chemosphere.pdf