The role of phenothiazine derivatives in autophagy regulation: A systematic review.

In this review, we summarized the current literature on the impact of phenothiazine derivatives on autophagy in vitro. Phenothiazines are antipsychotic drugs used in the treatment of schizophrenia, which is related to altered neurotransmission and dysregulation of neuronal autophagy. Thus, phenothiazine derivatives can impact autophagy. We identified 35 papers, where the use of the phenothiazines in the in vitro autophagy assays on normal and cancer cell lines, Caenorhabditis elegans, and zebrafish were discussed. Chlorpromazine, fluphenazine, mepazine, methotrimeprazine, perphenazine, prochlorperazine, promethazine, thioridazine, trifluoperazine, and novel derivatives can modulate autophagy. Stimulation of autophagy by phenothiazines may be either mammalian target of rapamycin (mTOR)-dependent or mTOR-independent. The final effect depends on the used concentration as well as the cell line. A further investigation of the mechanisms of autophagy regulation by phenothiazine derivatives is required to understand the biological actions and to increase the therapeutic potential of this class of drugs.

In vitro anticancer activity of fluphenazine, perphenazine and prochlorperazine. A review.

Drug repositioning is an approach that could accelerate the clinical use of compounds in different diseases. The goal is to take advantage of the fact that approved drugs have been tested on humans and detailed information is available on their pharmacology, toxicity and formulation. It can significantly reduce the costs and time needed to implement necessary therapies on the market. In recent years, phenothiazines are being tested for cancer, viral, bacterial, fungal and other diseases. Most research focuses on chlorpromazine as a model drug in this class, but other drugs such as fluphenazine, perphenazine and prochlorperazine have been proven to inhibit the viability of different cancer cell lines. In this study, we performed an extensive literature search to find and summarize all papers on the chosen phenothiazines and their potential in treating different types of cancerin vitro for further animal/clinical trials. Fluphenazine, perphenazine and prochlorperazine possess anticancer activity towards different types of human cancer. The antitumor activity is mainly mediated by an effect of the drugs on the cell cycle, proliferation or apoptosis. Possible molecular targets of phenothiazine derivatives are the drug's efflux pumps (ABCB1 and P-glycoprotein) and two parallel pathways (AKT and Wnt) regulated by the D2 receptor antagonists. The drugs have the potential to reduce the viability of human cancer cell lines, fragment the DNA, stimulate apoptosis, inhibit cell migration and invasiveness as well as impair the production of reactive oxygen species. In addition, due to the sedative and antiemetic properties antipsychotics can be used as an adjuvant for the treatment of chemotherapy side effects.

Polyphenols' Cardioprotective Potential: Review of Rat Fibroblasts as Well as Rat and Human Cardiomyocyte Cell Lines Research.

According to the World Health Organization, cardiovascular diseases are responsible for 31% of global deaths. A reduction in mortality can be achieved by promoting a healthy lifestyle, developing prevention strategies, and developing new therapies. Polyphenols are present in food and drinks such as tea, cocoa, fruits, berries, and vegetables. These compounds have strong antioxidative properties, which might have a cardioprotective effect. The aim of this paper is to examine the potential of polyphenols in cardioprotective use based on in vitro human and rat cardiomyocytes as well as fibroblast research. Based on the papers discussed in this review, polyphenols have the potential for cardioprotective use due to their multilevel points of action which include, among others, anti-inflammatory, antioxidant, antithrombotic, and vasodilatory. Polyphenols may have potential use in new and effective preventions or therapies for cardiovascular diseases, yet more clinical studies are needed.

Cardioprotective Activity of Selected Polyphenols Based on Epithelial and Aortic Cell Lines. A Review.

Polyphenols have recently gained popularity among the general public as products and diets classified as healthy and containing naturally occurring phenols. Many polyphenolic extracts are available on the market as dietary supplements, functional foods, or cosmetics, taking advantage of clients' desire to live a healthier and longer life. However, due to the difficulty of discovering the in vivo functions of polyphenols, most of the research focuses on in vitro studies. In this review, we focused on the cardioprotective activity of different polyphenols as possible candidates for use in cardiovascular disease therapy and for improving the quality of life of patients. Thus, the studies, which were mainly based on endothelial cells, aortic cells, and some in vivo studies, were analyzed. Based on the reviewed articles, polyphenols have a few points of action, including inhibition of acetylcholinesterase, decrease in reactive oxygen species production and endothelial tube formation, stimulation of acetylcholine-induced endothelium-derived mediator release, and others, which lead to their cardio- and/or vasoprotective effects on endothelial cells. The obtained results suggest positive effects of polyphenols, but more long-term in vivo studies demonstrating effects on mechanism of action, sensitivity, and specificity or efficacy are needed before legal health claims can be made.

E-cigarettes: voltage- and concentration-dependent loss in human lung adenocarcinoma viability.

E-cigarettes are used by millions of people despite the fact that the harmful effect of aerosol emitted from these products to the human organism is still not clear. In this paper, toxicity of vapor generated using different solutions and battery output voltage on A549 cells viability is presented. The obtained EC50 values for commercially available propylene glycol/glycerol solution 1:1 e-liquids based on 3.2 V (0.127%), 4.0 V (0.112%) and 4.8 V (0.038%) were about 1.5-4.5 times higher than in tobacco smoke (0.0086%). Furthermore, it was shown that the increase of battery output voltage decreased A549 cell viability. In addition, commercially available extracts were more cytotoxic than laboratory made extracts. Owing to the expansiveness of e-cigarettes, it is very important to estimate their impact on public health. Our results not only confirm less cytotoxicity of e-liquid aerosol than cigarette smoke, but also demonstrate that solutions used in e-liquids and, for the first time, battery output voltage have a significant impact on cytotoxicity of e-cigarette vapor. Thus, the results of this study are very important for the current and future legal regulations on e-cigarettes.

Effect of fluoroquinolones on melanogenesis in normal human melanocytes HEMn-DP: a comparative in vitro study.

PURPOSE: Fluoroquinolones are one of the most commonly prescribed classes of antibiotics. However, their use is often connected with high risk of phototoxic reactions that lead to various skin or eye disorders. The aim of this study was to examine the effect of ciprofloxacin, lomefloxacin, moxifloxacin and fluoroquinolone derivatives with different phototoxic potential, on the viability and melanogenesis in melanocytes. MATERIALS AND METHODS: Normal human epidermal melanocytes, dark pigmented (HEMn-DP) were used as an in vitro model system. The effect of the tested antibiotics on cell viability and melanization in pigmented cells was investigated using a spectrophotometric method. The WST-1 assay was used to detect the cytotoxic effect of antibiotics. RESULTS: Ciprofloxacin, lomefloxacin and moxifloxacin induced the concentration-dependent loss in melanocytes viability. The values of EC50 for the tested fluoroquinolone derivatives were found to be 2.0 mM for ciprofloxacin, 0.51 mM for lomefloxacin and 0.27 mM for moxifloxacin. The exposure of cells to different concentrations of the analyzed drugs resulted in decrease in melanin content and tyrosinase activity. The highest decrease was observed for lomefloxacin which may explain its high phototoxic potential in vivo. The role of melanin in the mechanism of the toxicity of fluoroquinolones was discussed and the obtained results were compared with the previously obtained data concerning light-pigmented melanocytes (HEMa-LP). CONCLUSIONS: The results obtained in vitro suggest that the phototoxic potential of fluoroquinolones in vivo depends on specific drug-melanin interaction, the ability of drugs to affect melanogenesis as well as on the degree of melanocytes pigmentation.

The effect of simultaneous exposure of HEMn-DP and HEMn-LP melanocytes to nicotine and UV-radiation on the cell viability and melanogenesis.

Nicotine is a main compound of tobacco plants and may affect more than a billion people all over the world that are permanently exposed to nicotine from cigarettes, various forms of smoking cessation therapies, electronic cigarettes or second-hand smoke. It is known that nicotine forms complexes with melanin what may lead to accumulation of this alkaloid in tissues of living organisms containing the pigment. This may affect the viability of cells and process of melanin biosynthesis that takes place in melanocytes. Although UV radiation is known to be a particular inductor of melanin biosynthesis, its simultaneous effect with nicotine on this process as well as the viability of human cells containing melanin have not been assessed so far. The aim of this study was to examine the simultaneous impact of nicotine and UV radiation on viability and melanogenesis in cultured normal human melanocytes dark (HEMn-DP) and light (HEMn-LP) pigmented. Nicotine together with UV radiation induced concentration-dependent loss in melanocytes viability. The higher cell loss was observed in dark pigmented melanocytes in comparison to light pigmented cells. Simultaneous exposure of cells to nicotine and UV radiation also caused changes in melanization process in both tested cell lines. The data suggest that simultaneous exposure of melanocytes to nicotine and UV radiation up-regulates melanogenesis and affects cell viability. Observed processes are more pronounced in dark pigmented cells.

FLUPHENAZINE AND PERPHENAZINE IMPACT ON MELANOGENESIS AND ANTIOXIDANT ENZYMES ACTIVITY IN NORMAL HUMAN MELANOCYTES.

Fluphenazine and perphenazine as a phenothiazine-class antipsychotic drugs are widely used to treat psychoses and schizophrenia, however their use is associated with significant side effects such as extrapyramidal symptoms as well as ocular and skin disorders. The aim of this study was to examine the effect of fluphenazine and perphenazine on cell viability, melanogenesis and antioxidant defense system in normal human melanocytes. It has been shown that both phenothiazines induce concentration-dependent loss in cell viability. The value of EC50. was calculated to be 1.24 and 2.76 µM for fluphenazine and perphenazine, respectively. Fluphenazine in concentration of 1.0 µM and perphenazine in concentrations of 1.0 and 3.0 µM inhibied melanogenesis and decreased microphthalmia-associated transcription factor content. To study the effect of both analyzed drugs on antioxidant defense system in melanocytes, the level of hydrogen peroxide and the activities of antioxidant enzymes: superoxide dismutase, catalase and glutathione peroxidase were determined. Fluphenazine and perphenazine in higher analyzed concentrations caused depletion of melanocytes antioxidant status, what indicated the induction of oxidative stress. The observed changes in melanization process and antioxidant defense system in pigmented cells exposed to fluphenazine and perphenazine in vibo suggest a significant role of melanin and melanocytes in the mechanisms of undesirable side effects of these drugs in vivo, especially directed to pigmented tissues. Moreover, the presented differences in modulation of biochemical processes in melanocytes may be an explanation for various toxic activity of the analyzed phenothiazine derivatives in vivo.

EFFECT OF PARACETAMOL ON MELANIZATION PROCESS IN HUMAN EPIDERMAL MELANOCYTES.

Paracetamol (acetaminophen) is commonly used as a drug of choice for treatment of pain and fever. Unlike non-steroidal anti-inflammatory drugs (NSAIDs) it does not cause gastrointestinal damage or untoward cardiorenal effects, however cutaneous adverse effects have been reported. It is known that paracetamol binds to melanin biopolymers, but the relation between the affinity of this drug to melanin and its toxicity is not documented. The aim of this work was to examine the impact of paracetamol on melanogenesis in cultured human normal epidermal melanocytes (HEMn-DP). The effect of paracetamol on cell viability was determined by WST-1 assay, melanin content and tyrosinase activity were measured spectrophotometrically. It has been demonstrated that paracetamol induced concentration-dependent loss in melanocytes viability. The value of EC50 was found to be - 20.0 mM. The analyzed drug inhibited melanin biosynthesis in a concentration-dependent manner by decreasing the melanin content as well as the tyrosinase activity. The demonstrated inhibitory effect of paracetamol on melanization process in normal epidermal melanocytes in vitro may explain the potential role of melanin biopolymer in the mechanisms of undesirable side effects of this drug in vivo, as a result of its accumulation in pigmented tissues.

Effect of norfloxacin and moxifloxacin on melanin synthesis and antioxidant enzymes activity in normal human melanocytes.

Fluoroquinolone antibiotics provide broad-spectrum coverage for a number of infectious diseases, including respiratory as well as urinary tract infections. One of the important adverse effects of these drugs is phototoxicity which introduces a serious limitation to their use. To gain insight the molecular mechanisms underlying the fluoroquinolones-induced phototoxic side effects, the impact of two fluoroquinolone derivatives with different phototoxic potential, norfloxacin and moxifloxacin, on melanogenesis and antioxidant enzymes activity in normal human melanocytes HEMa-LP was determined. Both drugs induced concentration-dependent loss in melanocytes viability. The value of EC50 for these drugs was found to be 0.5 mM. Norfloxacin and moxifloxacin suppressed melanin biosynthesis; antibiotics were shown to inhibit cellular tyrosinase activity and to reduce melanin content in melanocytes. When comparing the both analyzed fluoroquinolones, it was observed that norfloxacin possesses greater inhibitory effect on tyrosinase activity in melanocytes than moxifloxacin. The extent of oxidative stress in cells was assessed by measuring the activity of antioxidant enzymes: SOD, CAT, and GPx. It was observed that norfloxacin caused higher depletion of antioxidant status in melanocytes when compared with moxifloxacin. The obtained results give a new insight into the mechanisms of fluoroquinolones toxicity directed to pigmented tissues. Moreover, the presented differences in modulation of biochemical processes in melanocytes may be an explanation for various phototoxic activities of the analyzed fluoroquinolone derivatives in vivo.

EPR spectroscopy of chlorpromazine-induced free radical formation in normal human melanocytes.

The purpose of this study was to estimate the effect of chlorpromazine on free radical concentration in HEMn-DP melanocytes using electron paramagnetic resonance (EPR) spectroscopy. It was found that chlorpromazine at concentrations of 1 × 10(-7) and 1 × 10(-6) M contributed to the formation of free radicals (g values ~2) in a dose-dependent manner. The increase in free radical formation was accompanied by an increase in cytotoxicity, as shown by a tetrazolium assay. Homogeneous broadening of EPR lines, slow spin-lattice relaxation processes, and strong dipolar interactions characterized all the tested cellular samples. The performed examination of free radical formation in cells exposed to different chlorpromazine concentrations confirmed the usefulness of electron paramagnetic resonance spectroscopy to determine the effect of a drug on free radical production in a cellular model system in vitro.

Gentamicin affects melanogenesis in normal human melanocytes.

BACKGROUND: Aminoglycoside antibiotics, including gentamicin, despite their ability to induce adverse effects on pigmented tissues, remain valuable and sometimes indispensable for the treatment of various infections. It is known that gentamicin binds to melanin biopolymers, but the relation between this drug affinity to melanin and its toxicity is not well documented. The aim of this work was to examine the impact of gentamicin on viability and melanogenesis in HEMa-LP (light pigmented) and HEMn-DP (dark pigmented) normal human melanocytes. METHODOLOGY/PRINCIPAL FINDINGS: The effect of gentamicin on cell viability was determined by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay; melanin content and tyrosinase activity were measured spectrophotometrically. It has been demonstrated that gentamicin induces concentration-dependent loss in melanocytes viability. The application of antibiotic in concentration of 10 mM causes higher reduction in viability of the light pigmented melanocytes (by about 74%) when compared with the dark pigmented ones (by about 62%). The value of the concentration of a drug that produces loss in cell viability by 50% (EC50) for both cell lines was found to be ∼7.5 mM. It has been shown that gentamicin causes inhibition of tyrosinase activity and reduces melanin content in light pigmented melanocytes significantly more than in the dark pigmented cells. CONCLUSION/SIGNIFICANCE: We have found that gentamicin modulates melanization process in melanocytes in vitro, what may explain the potential role of melanin biopolymer in the mechanisms of undesirable toxic effects of this drug in vivo, as a result of its accumulation in pigmented tissues. We have also stated that the melanogenesis process in light pigmented melanocytes is more sensitive to the inhibitory effect of gentamicin than in the dark pigmented cells.

IMPACT OF GENTAMICIN ON ANTIOXIDANT ENZYMES ACTIVITY IN HEMn-DP CELLS.

Aminoglycoside antibiotics, including gentamicin, are widely used clinically in treatment of bacterial infections. Unfortunately, their side effects, especially nephrotoxicity and ototoxicity remain a problem. It is known that aminoglycoside antibiotics bind well to melanin biopolymer, but the relation between their affinity to melanin and ototoxicity is not well documented. The aim of this work was to examine the impact of gentamicin on antioxidant enzymes activity in cultured dark pigmented normal human melanocytes (HEMn-DP). The WST-1 assay was used to detect gentamicin cytotoxic effect. The analyzed antibiotic induced concentration-dependent loss in melanocytes viability. The value of EC50 was found to be 7.5 mM. Significant changes in the cellular antioxidant enzymes: SOD, CAT and GPx were stated in melanocytes exposed to gentamicin, what may indicate the depletion of antioxidant defense system. It is concluded, that the results obtained in vitro may explain a potential role of melanocytes and melanin in the causative mechanisms of aminoglycosides ototoxic effects in vivo.

Nicotine impact on melanogenesis and antioxidant defense system in HEMn-DP melanocytes.

Nicotine is a compound of tobacco plants and is responsible for addictive properties of tobacco which is used by about one billion of smokers all over the world. Recently, nicotine has drawn even more attention due to its presumed neuroprotective and antioxidant features as far as common use in various forms of smoking cessation therapies. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn influence biochemical processes in human cells producing melanin. The aim of this study was to examine the impact of nicotine on melanogenesis and antioxidant defense system in cultured normal human melanocytes (HEMn-DP). Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC50 was determined to be 2.52 mM. Nicotine modulated melanin biosynthesis in normal human melanocytes. Significant changes in hydrogen peroxide content and cellular antioxidant enzymes: SOD, CAT, and GPx activities were stated in melanocytes exposed to nicotine, which indicates alterations of antioxidant defense system. The results obtained in vitro may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long-term exposition to nicotine.

Effect of nicotine on melanogenesis and antioxidant status in HEMn-LP melanocytes.

Nicotine is a natural ingredient of tobacco plants and is responsible for the addictive properties of tobacco. Nowadays nicotine is also commonly used as a form of smoking cessation therapy. It is suggested that nicotine may be accumulated in human tissues containing melanin. This may in turn affect biochemical processes in human cells producing melanin. The aim of this study was to examine the effect of nicotine on melanogenesis and antioxidant status in cultured normal human melanocytes HEMn-LP. Nicotine induced concentration-dependent loss in melanocytes viability. The value of EC50 was determined to be 7.43 mM. Nicotine inhibited a melanization process in human light pigmented melanocytes and caused alterations of antioxidant defense system. Significant changes in cellular antioxidant enzymes: superoxide dismutase and catalase activities and in hydrogen peroxide content were stated. The obtained results may explain a potential influence of nicotine on biochemical processes in melanocytes in vivo during long term exposition to nicotine.

[Hypomelanoses transmitted from generation to generation]. / Hipomelanozy przekazywane z pokolenia na pokolenie.

Inherited diseases of pigmentation were among the first traits studied in humans because of their easy recognition. This article presents selected hypopigmentary disorders, which can be divided into hypomelanocytoses and hypomelanoses. Hereditary hypomelanoses are caused by abnormal melanin biosynthesis as well as by abnormal transfer of mature melanosomes to melanocyte dendrites and to neighboring cells. These disorders are represented by oculocutaneous albinism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Griscelli syndrome, Menkes syndrome and phenylketonuria, and are caused by different mutations of the following genes: TYR, P, TRP1, MATP, HPS, CHS, MYO5A, RAB27A, MLPH, ATP7A and PAH. Oculocutaneous albinism is caused by a deficiency of melanin pigment in the skin, hair, and eye and results from mutations in the TYR, P, TRP1 and MATP genes involved in the biosynthesis of melanin pigment. Mutations in the HPS, CHS, MYO5A, RAB27A and MLPH genes, which regulate the biogenesis, maturation and transfer of me-lanosomes to neighboring cells, are responsible for such disorders as Hermansky-Pudlak, Chediak-Higashi and Griscelli syndromes. In turn, mutations of the ATP7A and PAH genes, regulating intracellular copper concentration and activity of phenylalanine hydroxylase, lead to Menkes syndrome and phenylketonuria.

Targeting autophagy by antipsychotic phenothiazines: potential drug repurposing for cancer therapy.

Cancer is recognized as the major cause of death worldwide and the most challenging public health issues. Tumor cells exhibit molecular adaptations and metabolic reprograming to sustain their high proliferative rate and autophagy plays a pivotal role to supply the high demand for metabolic substrates and for recycling cellular components, which has attracted the attention of the researchers. The modulation of the autophagic process sensitizes tumor cells to chemotherapy-induced cell death and reverts drug resistance. In this regard, many in vitro and in vivo studies having shown the anticancer activity of phenothiazine (PTZ) derivatives due to their potent cytotoxicity in tumor cells. Interestingly, PTZ have been used as antiemetics in antitumor chemotherapy-induced vomiting, maybe exerting a combined antitumor effect. Among the mechanisms of cytotoxicity, the modulation of autophagy by these drugs has been highlighted. Therefore, the use of PTZ derivatives can be considered as a repurposing strategy in antitumor chemotherapy. Here, we provided an overview of the effects of antipsychotic PTZ on autophagy in tumor cells, evidencing the molecular targets and discussing the underlying mechanisms. The modulation of autophagy by PTZ in tumor cells have been consistently related to their cytotoxic action. These effects depend on the derivative, their concentration, and also the type of cancer. Most data have shown the impairment of autophagic flux by PTZ, probably due to the blockade of lysosome-autophagosome fusion, but some studies have also suggested the induction of autophagy. These data highlight the therapeutic potential of targeting autophagy by PTZ in cancer chemotherapy.

Impact of kanamycin on melanogenesis and antioxidant enzymes activity in melanocytes--an in vitro study.

Aminoglycosides, broad spectrum aminoglycoside antibiotics, are used in various infections therapy due to their good antimicrobial characteristics. However, their adverse effects such as nephrotoxicity and auditory ototoxicity, as well as some toxic effects directed to pigmented tissues, complicate the use of these agents. This study was undertaken to investigate the effect of aminoglycoside antibiotic-kanamycin on viability, melanogenesis and antioxidant enzymes activity in cultured human normal melanocytes (HEMa-LP). It has been demonstrated that kanamycin induces concentration-dependent loss in melanocytes viability. The value of EC50 was found to be ~6.0 mM. Kanamycin suppressed melanin biosynthesis: antibiotic was shown to inhibit cellular tyrosinase activity and to reduce melanin content in normal human melanocytes. Significant changes in the cellular antioxidant enzymes: SOD, CAT and GPx were stated in melanocytes exposed to kanamycin. Moreover, it was observed that kanamycin caused depletion of antioxidant defense sytem. It is concluded that the inhibitory effect of kanamycin on melanogenesis and not sufficient antioxidant defense mechanism in melanocytes in vitro may explain the potential mechanisms of undesirable side effects of this drug directed to pigmented tissues in vivo.

Effect of streptomycin on melanogenesis and antioxidant status in melanocytes.

Streptomycin is an aminoglycoside antibiotic with an antituberculosis activity commonly used in clinical practice due to its good antimicrobial characteristics. A well-known undesirable side effect of this drug is ototoxicity, which may be caused by overproduction of reactive oxygen species and loss of melanocytes in the inner ear. The aim of this study was to examine the effect of streptomycin on melanogenesis and antioxidant defense system in cultured normal human melanocytes (HEMa-LP). Streptomycin induced concentration-dependent loss in melanocytes viability. The value of EC50 was determined to be ~5.0 mM. It has been shown that streptomycin causes inhibition of tyrosinase activity and reduces melanin content in human melanocytes in a concentration-dependent manner. Significant changes in the activity of cellular antioxidant enzymes: superoxide dismutase, catalase, and glutathione peroxidase were also stated. The results obtained in vitro may explain a potential role of melanocytes and melanin in the causative mechanisms of aminoglycosides ototoxic effects in vivo.

[Hereditary hypomelanocytoses: the role of PAX3, SOX10, MITF, SNAI2, KIT, EDN3 and EDNRB genes]. / Hipomelanocytozy dziedziczne: rola genów PAX3, SOX10, MITF, SNAI2, KIT, EDN3 i EDNRB.

Hypo- and hyperpigmentation disorders are the most severe dermatological diseases observed in patients from all over the world. These disorders can be divided into melanoses connected with disorders of melanocyte function and melanocytoses connected with melanocyte development. The article presents some hereditary hypomelanocytoses, which are caused by abnormal melanoblast development, migration and proliferation as well as by abnormal melanocyte viability and proliferation. These disorders are represented by Waardenburg syndrome, piebaldism and Tietz syndrome, and are caused by different mutations of various or the same genes. The types of mutations comprise missense and nonsense mutations, frameshifts (in-frame insertions or deletions), truncating variations, splice alterations and non-stop mutations. It has been demonstrated that mutations of the same gene may cause different hypopigmentation syndromes that may have similar phenotypes. For example, mutations of the MITF gene cause Waardenburg syndrome type 2A as well as Tietz syndrome. It has also been demonstrated that mutations of different genes may cause an identical syndrome. For example, mutations of MITF, SNAI2 and SOX10 genes are observed in Waardenburg syndrome type II and mutations of EDNRB, EDN3 and SOX10 genes are responsible for Waardenburg syndrome type IV. In turn, mutation of the KIT gene and/or heterozygous deletion of the SNAI2 gene result in piebaldism disease. The knowledge of the exact mechanisms of pigmentary disorders may be useful in the development of new therapeutic approaches to their treatment.