Melanosis Coli: Beyond Laxatives, What Are The Triggers?

Melanosis coli is a benign condition in which the lining of the colon and rectum turns a shade of black or brown. While the biggest risk factor for melanosis coli is frequent laxative use, there are other factors that can cause this condition. These include irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colonic neoplasms, hyperplastic polyps, non-steroidal anti-inflammatory drugs (NSAIDs), vitamin E (VE) deficiency, the intake of unsaturated fatty acids, environmental factors, family history, psoriasis, and Rett syndrome.

Chronic constipation

There are many different causes of chronic constipation. It can be caused by structural lesions of the colon, such as colon cancer, colon stricture, or narrowing. It can also be caused by medical conditions such as diabetes, thyroid disorders, Parkinson's disease, or pregnancy. Certain medications can also lead to chronic constipation, including pain medications (narcotics), blood pressure medications (calcium channel blockers), anti-seizure medications, and antispasmodics. In people over 50, chronic constipation may be a sign of a more serious bowel disease or structural disorder, so it is important to consult a healthcare professional.

To improve chronic constipation, it is recommended to increase fibre intake through diet or supplements, increase fluid intake, and exercise regularly. In more moderate to severe cases, medications or laxatives may be necessary. However, it is important to note that laxatives should be used carefully and for short periods of time, as prolonged use can lead to dependence and further aggravate constipation.

Intestinal dysfunction

Anthraquinone laxatives can result in the displacement of electrolytes and water loss in the intestinal tract. This, in turn, leads to the deposition of protein products, which can cause intestinal dysfunction. Changes in sympathetic function, electrolyte disorders, and decreased water absorption can also lead to intestinal dysfunction. The unabsorbed residues deposit in the intestine, forcing the intestinal mucosa to fill with large quantities of black or brown pigment.

The use of anthraquinone laxatives can also cause direct toxic effects on colonic epithelial cells, which can produce lipofuscin, a dark pigment. This is engulfed by nearby macrophages, which then generate tumour necrosis factor-alpha (TNF-a). This produces toxic effects on capillary vessels and damages neurons, inducing cell swelling and decomposition.

The treatment for melanosis coli involves stopping the use of laxatives, and it may take up to a year for the condition to resolve.

Direct toxic effects of drugs on epithelial cells

Melanosis coli is a benign condition in which the membranes lining the colon and rectum are discoloured, usually a dark brown or black colour. It is caused by pigment deposits in the lamina propria, a layer of the intestinal lining. While the condition is harmless and reversible, it is often indicative of laxative abuse, particularly those containing anthraquinones. Anthraquinones in laxatives have a direct toxic effect on the epithelial cells of the colon. When these laxative molecules turn into their active form in the large bowel, they can cause cell damage to the lining of the large bowel, leading to cell death.

Anthraquinone laxatives are widely available over the counter and are the primary cause of melanosis coli. They are products that stimulate the colon to pass stool more quickly and contain ingredients like senna, aloe, rhubarb, cascara sagrada, and frangula. Research published in the Indonesian Journal of Gastroenterology Hepatology and Digestive Endoscopy suggests that 70% of people who frequently take anthraquinone laxatives will develop melanosis coli, often within a few months of use.

The direct toxic effects of anthraquinone laxatives on epithelial cells are as follows:

• They stimulate the active transport of chloride into the gut, which in turn causes an osmotic gradient and pulls water into the gut lumen.
• They inhibit Na-K ATPase on the enterocytes, which further inhibits the reabsorption of water, sodium, and potassium, ultimately excreting it into the faeces.
• They stimulate local prostaglandins, which stimulate peristalsis and decrease transit time through the bowel.

The adverse effects of anthraquinone laxatives, particularly senna and other stimulant laxatives, include hypovolemia, leading to dizziness, palpitation, and syncope; miscarriages in women; and decreased absorption of oral medications due to uptake inhibition.

Melanosis coli is usually diagnosed during a colonoscopy or sigmoidoscopy, which are procedures that explore the colon. It is important to differentiate melanosis coli from other conditions that can cause similar pigmentation changes, such as Peutz-Jeghers Syndrome, an autosomal dominant disorder that increases the risk of colon cancer.

The treatment for melanosis coli is to discontinue the use of laxatives. The condition typically resolves within 6 to 12 months. Preventing constipation and subsequent laxative use is key to preventing melanosis coli. This can be achieved through dietary and lifestyle modifications, such as increasing fibre and fluid intake, and regular physical activity.

Changes in gene expression

Melanosis coli (MC) is a condition characterised by abnormal brown or black pigmentation deposits on the colonic mucosa. The specific genes associated with the pathogenesis of MC are not yet fully understood. However, a study published in 2015 by Xiao-An Li et al. revealed some interesting insights into the genes involved in MC.

The study by Li et al. aimed to examine the histopathological features and differentially expressed genes associated with MC. The researchers performed a range of analyses, including DNA expression microarray analysis, western blotting, and immunofluorescence assays, on tissue samples from patients diagnosed with MC.

The results of the study identified several genes that were significantly downregulated in MC. These included CYP3A4, CYP3A7, UGT2B11, and UGT2B15. These genes belong to the cytochrome P450 superfamily, which plays a crucial role in the metabolism of xenobiotics and drugs.

The CYP3A4 gene, in particular, was found to be downregulated in MC compared to normal tissue. This gene is predominantly present in the intestine and is involved in the metabolism of various clinical drugs. The study's findings suggest that long-term use of anthraquinone laxatives may inhibit the expression of CYP3A4 and other cytochrome P450-associated genes in the intestine.

In summary, the study by Li et al. provided novel insights into the genes associated with MC, specifically highlighting the downregulation of cytochrome P450-related genes. Further research is needed to build upon these findings and fully elucidate the genetic basis of MC.

Irritable bowel syndrome

Melanosis coli is a condition in which the membranes lining the colon and rectum become discoloured, usually a dark brown or black shade. It is a harmless, benign condition that does not cause colorectal cancer. The discolouration is caused by a build-up of a pigment called lipofuscin, which is associated with the ageing process and cell death.

The biggest risk factor for melanosis coli is the frequent use of laxatives, particularly anthraquinone-based laxatives. These are often used by people who are constipated and include products containing senna, aloe and rhubarb. Research suggests that 70% of people who frequently take these types of laxatives will develop melanosis coli within a few months of use.

However, melanosis coli has also been observed in patients who do not use laxatives. For example, it has been reported in patients with inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's colitis. This raises the possibility that chronic colitis could cause melanosis coli even in the absence of laxative use.

In terms of irritable bowel syndrome (IBS), this is a common disorder that can cause a range of digestive symptoms, including abdominal pain, bloating, diarrhoea and constipation. While melanosis coli has been observed in patients with IBD, it is unclear whether there is a direct link between IBS and melanosis coli. However, it is important to note that constipation, which is a symptom of IBS, can increase the risk of melanosis coli if it leads to frequent laxative use.

If you are experiencing symptoms of IBS or are concerned about constipation or melanosis coli, it is recommended that you consult a healthcare professional for personalised advice and guidance.

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