Investigating the effect of Diindolylmethane on HPV and cancers caused by it

IntroductionDiindolylmethane (DIM) is the primary metabolite of the medicinally active acid indole-۳-carbinol (I۳C) found in many brassica vegetables via the parent compound glucobrassicin. Ingested glucobrassicin is catalyzed by the enzyme myrosinase stored in the vegetable and It is converted to Indole-۳-Carbinol, which is rapidly digested in the human stomach through acid-mediated condensation reactions to DIM and other metabolites. Diindolylmethane does not exist in its final form. In the human body, it is metabolized by precursors such as the plant substance indole-۳-carbinol, which is directly metabolized to diindolylmethane, and glugravicin, which is indirectly metabolized because it is a direct precursor of indole-۳-carbinol. Both are precursors of phytochemicals produced in some types of vegetables. When we consume rich sources of the phytochemical glugravicin, the enzyme myrosinase stimulates the release of indole-۳-carbinol. In the acidic environment of the stomach, indole-۳-carbinol reacts with indolines and forms diindolylmethane. Indole-۳-carbinol is highly reactive and unstable in the human body, meaning that a small fraction of it is metabolized to diindolemethane. Therefore, it is recommended to use pure diindolylmethane, which is more stable in the stomach. Diindolylmethane is a fat-soluble substance that is metabolized in the human body in a similar way to other phytochemicals such as lutein and lycopene. For better absorption through the digestive system, consumption of diindolylmethane with vegetable fats is recommended. In general, DIM has a relatively high absorption in the body. The main mechanism of DIM's effect is related to its effect on certain proteins in the body that are closely related to inflammation, estrogen regulation, androgen receptors, anti-viral and anti-cancer processes and are present in the following plants: Brussels sprouts, Mustard vegetable, Turnip, Cabbage, Red cabbage, Broccoli, radish, Cauliflower. Genital human papillomavirus infection is of interest to researchers and doctors due to its high prevalence in the human population, high contagiousness, and especially the ability of some HPV species to cause malignancy. This is especially true for cervical cancer (CC), which is one of the most common types of cancer in the Russian Federation and most of the world. Among the causes of death, malignant tumors of women over ۳۰ years of age took the first place. HPV is a group of more than ۲۰۰ related viruses, some of which are transmitted through vaginal, anal, or oral sex. Genital HPV types are divided into low-risk and high-risk groups. High-risk HPVs can cause different types of cancer. There are ۱۲ high-risk types of HPV: HPV ۱۶, ۱۸, ۳۱, ۳۳, ۳۵, ۳۹, ۴۵, ۵۱, ۵۲, ۵۶, ۵۸, and ۵۹. Two of these, HPV ۱۶ and HPV ۱۸, are responsible for more related cancers are HPV. Most HPV infections go away on their own without causing cancer: Your immune system usually controls HPV infections so that they are cleared by your body within a year or two . High-risk HPV infections that persist can cause cancer: Sometimes HPV infections are not successfully controlled by the immune system. When a high-risk HPV infection persists for years, it can lead to cell changes that, if left untreated, may worsen over time and become precancerous and then cancerous. HPV can cause six types of cancer: these include anal cancer, cervical cancer, oropharyngeal cancer, penile cancer, vaginal cancer, and vulvar cancer.MethodThe current review by searching in reliable books and useful databases such as Scopus, Elsevier, PubMed, Science Direct, Google Scholar, Mag Iran, Iran Dog, Iran Medex in the years ۲۰۱۳ to ۲۰۲۳ with keywords such as indolyl methane, warts Genital, HPV cancer, cervical cancer were done.FindingMechanistically, DIM appears to increase the activity of a gene repair enzyme that is reduced in some cancers, which is thought to provide protective effects. Acting on ۲-hydroxylation also appears to be relevant as it may produce an antiestrogenic effect. In mice, oral administration of indole-۳-carbinol (I۳C) for one week before induction of cancer by DMBA significantly reduced the incidence (۷۰-۹۰%) and multiplicity (۹۱-۹۶%) compared to the carcinogenic control. It shows efficacy on the direct carcinogen N-Nitroso-N-methylurea but to a lesser extent (۶۵% reduction in frequency). In one study (for ۲۵۰ days) spontaneous tumor growth, rather than toxin-induced tumor growth, appeared to occur in rats fed ۶۴ to ۱۲۸ mg/kg of I۳C in the diet (estimated intake by weight body (۴.۸-۹.۶ g/kg) is less than half. For control, it also decreases somewhat with multiplicity. In endometrial cancer-prone rats (Donryu rats) given dietary levels of indole-۳-carbinol (I۳C; ۲۰۰-۱۰۰۰ppm) and evaluated for a long-term experimental period, the rate of spontaneous uterine neoplasms after ۶۶۰ days It was significantly higher in the control group. (۳۸%) instead of low dose (I۳C (۲۵%) with ۶۰۰-۱۰۰۰ppm which is done equally (۱۴-۱۶%). This effect was observed along with increased ۲-hydroxylation of estradiol. Clinical (recovery of colposcopic status in ۸۳.۰% of patients), cytological (confirmed). (Absence of LSIL in ۹۸.۳% of women) and microbiological (HCR-HCR HPV negative in ۹۱.۵% of women) efficacy with satisfactory drug tolerance. Conclusion The therapeutic results obtained using the drug containing ۳, ۳'-diindolylmethane in the treatment of patients with low grade cervical intraepithelial lesions related to HPV can be considered satisfactory. Several animal studies (using DIM or its precursor I۳C) found anticancer effects on cancer cells. The aryl hydrocarbon receptor (AhR) plays a role in some immune cells, and in natural killer (NK) cells activation of this receptor (as seen with ۱۰ μM ۳,۳'-diindolylmethane) can increase production. IFN-γ increases the effective function, thereby inhibiting the growth of cancer cells.ConclusionAccording to our review study, based on biochemical reactions and effects in the body, di-indolyl methane can reduce and delay the progression of HPV to cancerous cells, so it is recommended to use it to increase cellular immunity and increase the protective strategy in people. Becomes infected with HPV.

کلیدواژه ها:

Diindolylmethane ، HPV ، cervical cancer