Nanoformulation of a Trypanocidal Drug Isometamidium Chloride Ameliorates the Apurinic-Apyrimidinic DNA Sites/Genotoxic Effects in Horse Blood Cells.
Abstract: Isometamidium chloride (ISM) is a trypanocide for the prophylactic and therapeutic use against vector-borne animal trypanosomosis (mainly Surra caused by ) and African animal trypanosomosis caused by //). ISM was found to be an efficient trypanocide for therapeutic/prophylactic use against trypanosomosis; however, it produces some local and systemic detrimental effects in animals. We synthesized isometamidium chloride-loaded alginate gum acacia nanoformulation (ISM SANPS) to lessen the detrimental side effects of isometamidium chloride (ISM) while treating trypanosomal diseases. We intended to determine the cytocompatibility/toxicity, and DNA deterioration/chromosomal structural or number changes (genotoxicity) of ISM SANPs using mammalian cells in a concentration-dependent manner. Apurinic/apyrimidinic (AP) sites are one of the major types of DNA lesions formed during base excision and repair of oxidized, deaminated, or alkylated bases. The intensity of the cellular AP site is an excellent marker of the deterioration of DNA quality. We thought it pertinent to quantify the AP sites in ISM SANPs-treated cells. Our investigations established a dose-dependent cyto-compatibility or toxicity and DNA impairment (genotoxicity) in ISM SANPs-treated horse peripheral blood mononuclear cells. ISM SANPs were biocompatible at various concentrations tested on the mammalian cells.
Publication Date: 2023-03-02 PubMed ID: 36976161PubMed Central: PMC10057175DOI: 10.3390/jox13010012Google Scholar: Lookup
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- Journal Article
Summary
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The study investigates a nanotechnology-based formulation of the drug Isometamidium chloride (ISM), which is used to treat trypanosomosis in animals. The new formulation is intended to reduce the drug’s side effects while maintaining its efficacy. The researchers assess the new drug formulation’s effect on DNA and chromosomes in mammalian cell samples.
Introduction and Background
- Trypanosomosis is a disease that affects animals, primarily caused by parasites. Isometamidium chloride (ISM) is a commonly used drug for its treatment.
- However, the standard ISM drug has several negative side effects including local and systemic effects in animals.
- To address this, the researchers created a new ISM formulation using nanotechnology. This new formula, called ISM-loaded alginate gum acacia nanoformulation (ISM SANPs), aimed to lessen the side effects of the drug whilst maintaining effectiveness against trypanosomosis.
Objectives and Methods
- The researchers intended to determine the cytocompatibility/toxicity and genotoxicity (DNA and chromosome changes) of ISM SANPs using mammalian cells in a concentration-dependent manner.
- The intensity of cellular apurinic/apyrimidinic (AP) sites, gaps in the DNA sequence, is a useful marker of DNA integrity. Therefore, the team decided to measure these sites to assess the DNA damage caused by ISM SANPs.
Results and Findings
- The researchers found that exposure to ISM SANPs resulted in a dose-dependent cytotoxicity in horse peripheral blood mononuclear cells. This means that higher concentrations of the drug were toxic to cells while lower doses were compatible and safe.
- They also found dose-dependent genotoxicity, with higher doses causing more DNA damage, indicated by the higher number of AP sites.
- However, ISM SANPs were found to be biocompatible at various concentrations tested on mammalian cells, suggesting the nanoformulation ameliorates some of the negative side effects of traditional ISM.
Implications of the Study
- The results reinforce the use of nanotechnology in drug formulation to reduce side effects while maintaining efficacy, an area of particular importance in veterinary medicine for the treatment of diseases like trypanosomosis.
- Further research could explore in greater detail the genomic effects of ISM SANPs, and the optimal dosage that maximizes efficacy while minimizing harm.
Cite This Article
APA
Singh S, Kumar B, Dilbaghi N, Devi N, Prasad M, Manuja A.
(2023).
Nanoformulation of a Trypanocidal Drug Isometamidium Chloride Ameliorates the Apurinic-Apyrimidinic DNA Sites/Genotoxic Effects in Horse Blood Cells.
J Xenobiot, 13(1), 148-158.
https://doi.org/10.3390/jox13010012 Publication
Researcher Affiliations
- ICAR-National Research Centre on Equines, Hisar 125001, Haryana, India.
- Department of Bio & Nano Technology, Guru Jambheshwar University of Science & Technology, Hisar 125001, Haryana, India.
- ICAR-National Research Centre on Equines, Hisar 125001, Haryana, India.
- Department of Bio & Nano Technology, Guru Jambheshwar University of Science & Technology, Hisar 125001, Haryana, India.
- ICAR-National Research Centre on Equines, Hisar 125001, Haryana, India.
- ICAR-National Research Centre on Equines, Hisar 125001, Haryana, India.
- ICAR-National Research Centre on Equines, Hisar 125001, Haryana, India.
Grant Funding
- SR/NM/NS-1064/2011 / Department of Science and Technology
Conflict of Interest Statement
The authors declare no conflict of interest.
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