Advances in Antitumor Effects Using Liposomal Citrinin in Induced Breast Cancer Model

Author:

Moura Michely Laiany Vieira1,de Menezes Ag-Anne Pereira Melo1,de Oliveira Filho José Williams Gomes1ORCID,do Nascimento Maria Luiza Lima Barreto1,dos Reis Antonielly Campinho1,Ribeiro Alessandra Braga2,da Silva Felipe Cavalcanti Carneiro1ORCID,Nunes Adriana Maria Viana3,Rolim Hercília Maria Lins4ORCID,de Carvalho Melo Cavalcante Ana Amélia1,Sousa João Marcelo de Castro e1ORCID

Affiliation:

1. Laboratory of Toxicological Genetics—LAPGENIC, Graduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina 64049-550, Brazil

2. CBQF—Centro de Biotecnologia e Química Fina—Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal

3. Department of Biophysics and Physiology, Federal University of Piauí, Teresina 64049-550, Brazil

4. Laboratory of Pharmaceutical Nanosystems—NANOSFAR, Graduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina 64049-550, Brazil

Abstract

The study aimed to evaluate the antitumor and toxicogenetic effects of liposomal nanoformulations containing citrinin in animal breast carcinoma induced by 7,12-dimethylbenzanthracene (DMBA). Mus musculus virgin females were divided into six groups treated with (1) olive oil (10 mL/kg); (2) 7,12-DMBA (6 mg/kg); (3) citrinin, CIT (2 mg/kg), (4) cyclophosphamide, CPA (25 mg/kg), (5) liposomal citrinin, LP-CIT (2 μg/kg), and (6) LP-CIT (6 µg/kg). Metabolic, behavioral, hematological, biochemical, histopathological, and toxicogenetic tests were performed. DMBA and cyclophosphamide induced behavioral changes, not observed for free and liposomal citrinin. No hematological or biochemical changes were observed for LP-CIT. However, free citrinin reduced monocytes and caused hepatotoxicity. During treatment, significant differences were observed regarding the weight of the right and left breasts treated with DMBA compared to negative controls. Treatment with CPA, CIT, and LP-CIT reduced the weight of both breasts, with better results for liposomal citrinin. Furthermore, CPA, CIT, and LP-CIT presented genotoxic effects for tumor, blood, bone marrow, and liver cells, although less DNA damage was observed for LP-CIT compared to CIT and CPA. Healthy cell damage induced by LP-CIT was repaired during treatment, unlike CPA, which caused clastogenic effects. Thus, LP-CIT showed advantages for its use as a model of nanosystems for antitumor studies.

Funder

CNPq

Publisher

MDPI AG

Subject

Pharmaceutical Science

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