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Therapeutic effects of iNOS inhibition against vitiligo in an animal model
Hamid Mansourpour1, Katayoun Ziari2, Sahar Kalantar Motamedi3
1Shahid Beheshti University of Medical Science, Tehran, Iran and AJA University of Medical Science, Tehran, Iran.
Abstract:
Nitric oxide (NO) is involved in several biological processes, but its role in human melanogenesis and vitiligo need further studies. Previous studies revealed that exposure to UVA and UVB were capable of the inducing nitric oxide production in keratinocytes and melanocytes through the activation of constitutive nitric oxide synthase, whereas inducible nitric oxide synthase overexpression has been reported to play an important role in hyperpigmentary disorders. The aim of this study was to evaluate iNOS inhibitor aminoguanidine (AG) as a therapeutic agent in our mouse model of vitiligo. In this study, male C57BL/6J Ler-vit/vit mice were purchased to evaluate the effect of iNOS inhibitor (aminoguanidine) (50 and 100 mg/kg) and L-arginine (100 mg/kg) in a mouse model of vitiligo induced by monobenzone 40%. Moreover, we used phototherapy device to treat the mice with NBUVB as a gold standard.The findings revealed that monobenzone was capable of inducing depigmentation after 6 weeks. However, aminoguanidine in combination with monobenzone was decrease the effect of monobenzone, while L-arginine play a key role in promoting the effect of monobenzone (P<0.001). Based on the phototherapy, the efficacy of phototherapy significantly increased by adding L-arginine (P<0.05). Taken together, we suggest that iNOS inhibitor can be a novel treatment for the prevention and treatment of vitiligo by combination of NBUVB therapy, furthermore; NO agents like L-arginine could also increase the effectiveness of phototherapy. Taken together, this pilot study showed significant repigmentation of vitiligous lesions treated with iNOS inhibitor plus NBUVB therapy, where other aspect including expression of an inducible iNOS, NO and TNF levels remained to be evaluated in mice model.
Insights
Aminoguanidine, an inducible nitric oxide synthase (iNOS) inhibitor, showed potential in preventing vitiligo depigmentation. Combining iNOS inhibitors with NBUVB phototherapy may offer a novel treatment strategy for vitiligo.
Area of Science:
- Dermatology
- Immunology
- Biochemistry
Background:
- Nitric oxide (NO) plays a role in melanogenesis, with implications for vitiligo pathogenesis.
- Inducible nitric oxide synthase (iNOS) overexpression is linked to hyperpigmentary disorders.
- The therapeutic potential of iNOS inhibition in vitiligo requires further investigation.
Purpose of the Study:
- To evaluate aminoguanidine (AG), an iNOS inhibitor, as a therapeutic agent for vitiligo.
- To assess the combined effects of AG and L-arginine with monobenzone-induced vitiligo in mice.
- To determine the efficacy of NBUVB phototherapy, with and without L-arginine, for vitiligo treatment.
Main Methods:
- A mouse model of vitiligo was induced using 40% monobenzone.
- Mice were treated with varying doses of aminoguanidine (50 and 100 mg/kg) or L-arginine (100 mg/kg).
- Narrowband ultraviolet B (NBUVB) phototherapy was administered as a gold standard treatment.
Main Results:
- Monobenzone successfully induced depigmentation within 6 weeks.
- Aminoguanidine mitigated the depigmenting effects of monobenzone.
- L-arginine promoted monobenzone's depigmenting effect and enhanced NBUVB phototherapy efficacy.
- Significant repigmentation was observed in vitiligous lesions treated with iNOS inhibitor plus NBUVB therapy.
Conclusions:
- iNOS inhibition, particularly with aminoguanidine, shows promise for vitiligo prevention and treatment.
- Combination therapy of iNOS inhibitors with NBUVB phototherapy may be a novel therapeutic approach for vitiligo.
- L-arginine can enhance the effectiveness of phototherapy, suggesting a role for NO modulation in vitiligo treatment.
