3,3'-Diindolylmethane for the Prevention and Treatment of Renal Fibrosis

By Kyle J. Norton


Renal fibrosis is a condition of kidney scars caused by improper healing of the kidney in regenerating damaged cells after an injury.

The process of kidney healing after injury involved serval overlapping phases, including inflammation, extracellular matrix (ECM) synthesis,  production and dissolving collagens,  regeneration, and remodeling.

Renal fibrosis over time may result in progressive loss of kidney function, leading to kidney failure in the advanced stage. 

Epidemiological studies suggested that age, gender, genetics, and perpetual activation of fibroblasts through priming are some of the prevalent factors that cause on the set of poor healing of kidney in the initiation of renal fibrosis.

Most patients with renal fibrosis are asymptomatic. Therefore, most cases of renal fibrosis are diagnosed at the advanced stage.

At this stage, patients may experience symptoms of chronic kidney disease (CKD), including weight loss and poor appetite. swollen ankles, feet or hands due to water retention, and blood in your urine. 

As of today, there are no effective treatments for preventing the progression of renal fibrosis. Treatments of renal fibrosis are to reduce symptoms and delay the disease progression of the disease.

3,3'-Diindolylmethane or DIM are phytochemicals derived from the digestion of indole-3-carbinol, belonging to the group of Indoles, found abundantly in broccoli, Brussels sprouts, cabbage, and kale, etc.


On finding a natural compound for the treatment of renal fibrosis with no side effects, researchers in the renal disease team led by the Renmin Hospital of Wuhan University examined 3,3'-Diindolylmethane (DIM), a natural acid condensation extracted from cruciferous plants, anti-fibrotic effects.

Selected rat kidney (NRK)-49F fibroblast cell mouse models induced renal fibrosis by a unilateral ureteral obstruction (UUO) and stimulated the production of transforming growth factor (TGF)-β1.

Where transforming growth factor (TGF)-β1 are inflammatory cytokines that frequently occur together during a regulatory T cell response.

According to the tested assays, treatment of DIM reduced kidney injury and production of interstitial collagens fibrosis.

Furthermore, DIM inhibited the expression of fibronectin involved in cell adhesion, growth, migration, and differentiation and increased fibronectin were found to associate with hypertrophic scars. and collagen-1 the collagen fiber involved the formation of scars.

Moreover, DIM promotes the expression of a protein associated with tumor suppression E-cadherin in the UUO model that protects the healing against the formation of scars.

DIM suppressed local fibroblast proliferation, a process that begins with a reaction to the clot associated with scar developing, observed by the scar contraction with the level of α-smooth muscle actin (α-SMA) and vimentin in scar tissue.

Additionally, DIM inhibited the renal fibrosis by significantly reduced the TGF-β1-induced proliferation of NRK49F cells in a time- and dose-dependent manner.

Interestingly, DIM decreased Smad2/3 phosphorylation associated with the excessive deposition of collagen and but increased Smad7 expression against keloid formation.

The results strongly suggested DIM inhibited the transforming growth factor (TGF)-β1 in the activation of proteins and genes associated with the formation of scarrings.

Dr. Xia ZE, the lead scientist said, " DIM inhibits TGF-β/Smad2/3 signaling to attenuate renal interstitial fibrosis via inhibiting local fibroblast activation".

Taken altogether, DIM may be considered a supplement for the prevention and treatment of renal fibrosis through its anti- renal scarring activity, pending to the confirmation fo larger sample size and multicenter human study.

Taken altogether, 3,3'-Diindolylmethane derived from the digestion of indole-3-carbinol may be considered a supplement for the prevention and treatment of renal fibrosis,, pending to the confirmation of the larger sample size and multicenter human study.

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Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)
Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.

Sources
(1) 3,3'-Diindolylmethane ameliorates renal fibrosis through the inhibition of renalfibroblast activation in vivo and in vitro by Xia ZE1, Xi JL2, Shi L. (PubMed)