BMC pharmacology & toxicology · 2025
Concentration-dependent effects of bacterial melanin on new superoxide-producing associates in rat tissues: a rotenone neurotoxic model of parkinson's disease.
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Danielyan Margarita, Karapetyan Kristine, Simonyan Ruzan, Simonyan Gegham, Babayan Madlena, Poghosyan Mikhail, Yekmalyan Hasmik, Simonyan Maxim, Simonyan Karen, Nebogova Kristina
Аннотация
BACKGROUND: Oxidative stress plays a central role in the degeneration of dopaminergic neurons and is a key factor in the pathogenesis of Parkinson's disease (PD). Therefore, antioxidant therapy represents a promising therapeutic strategy. This process involves numerous enzymes and signaling pathways that contribute to disease progression. In the present study, bacterial melanin (BM), known for its high biological activity and biostimulatory effects, was applied as a potential antioxidant. We examined quantitative and qualitative alterations in total fractions of biomembrane-associated components derived from rat tissue in a rotenone-induced PD model, under both low and high BM concentrations, along with an evaluation of their antioxidant properties.
METHODS: PD was induced via intracerebral rotenone injection, and the animals were maintained for 4 weeks. BM was administered twice during the survival period at concentrations of 4.5 mg/ml and 9 mg/ml. To confirm disease progression and evaluate potential therapeutic effects of BM, the Rotarod behavioral test was performed following a 4-week survival period. From the biomembranes of brain, lung, and small intestine tissues, superoxide-generating associates were isolated. Their specific amounts (mg/g) and steady-state concentrations of superoxide (O₂⁻) (M) were determined to assess oxidative stress. Antioxidant activity was quantified using the Coomassie Brilliant Blue (CBB) dye decoloration method.
RESULTS: The results demonstrated that BM exerted a membrane-stabilizing effect, with the 9 mg/ml dose proving more effective than 4.5 mg/ml. BM modulated membrane formation across the brain, lung, and small intestine by inhibiting the release of newly formed membrane-bound structures (NLP-Nox associates) and regulating the steady-state concentration of O₂⁻.Behavioral tests further confirmed the effectiveness of BM, with animal behavior parameters in the high-concentration group closely resembling those of the control group. It was found that different BM concentrations possess different antioxidant activity: specific activity at 4.5 mg/ml concentration amounted to 1.2 U/mg, while at 9 mg/ml it was 2.9 U/mg.
CONCLUSIONS: The results demonstrate BM's potential as both an antioxidant and membrane-stabilizing agent for PD treatment. The study revealed a concentration-dependent effect of BM's antioxidant activity in the PD model, with 9 mg/mL showing superior efficacy. Further research and clinical trials are warranted to validate its therapeutic efficacy.
CLINICAL TRIAL NUMBER: Not applicable.
METHODS: PD was induced via intracerebral rotenone injection, and the animals were maintained for 4 weeks. BM was administered twice during the survival period at concentrations of 4.5 mg/ml and 9 mg/ml. To confirm disease progression and evaluate potential therapeutic effects of BM, the Rotarod behavioral test was performed following a 4-week survival period. From the biomembranes of brain, lung, and small intestine tissues, superoxide-generating associates were isolated. Their specific amounts (mg/g) and steady-state concentrations of superoxide (O₂⁻) (M) were determined to assess oxidative stress. Antioxidant activity was quantified using the Coomassie Brilliant Blue (CBB) dye decoloration method.
RESULTS: The results demonstrated that BM exerted a membrane-stabilizing effect, with the 9 mg/ml dose proving more effective than 4.5 mg/ml. BM modulated membrane formation across the brain, lung, and small intestine by inhibiting the release of newly formed membrane-bound structures (NLP-Nox associates) and regulating the steady-state concentration of O₂⁻.Behavioral tests further confirmed the effectiveness of BM, with animal behavior parameters in the high-concentration group closely resembling those of the control group. It was found that different BM concentrations possess different antioxidant activity: specific activity at 4.5 mg/ml concentration amounted to 1.2 U/mg, while at 9 mg/ml it was 2.9 U/mg.
CONCLUSIONS: The results demonstrate BM's potential as both an antioxidant and membrane-stabilizing agent for PD treatment. The study revealed a concentration-dependent effect of BM's antioxidant activity in the PD model, with 9 mg/mL showing superior efficacy. Further research and clinical trials are warranted to validate its therapeutic efficacy.
CLINICAL TRIAL NUMBER: Not applicable.