Antitumor Profile of Combined Matricaria recutita Flower Extract and 5-Fluorouracil Chemotherapy in Sarcoma 180 In Vivo Model

Author:

Santos Sara A.1ORCID,Amaral Ricardo G.1ORCID,Graça Ariel S.1,Gomes Silvana V. F.2,Santana Fabrício P.2,de Oliveira Iza B.3ORCID,Andrade Luciana N.3ORCID,Severino Patrícia2ORCID,de Albuquerque-Júnior Ricardo L. C.4,Santos Sandra L.1,Souto Eliana B.56ORCID,Carvalho Adriana A.7

Affiliation:

1. Department of Physiology, Federal University of Sergipe, São Cristóvão CEP 49100-000, Brazil

2. Institute de Technology and Research (ITP), Tiradentes University, Aracaju CEP 49100-000, Brazil

3. Department of Medicine, Campus of Lagarto, Federal University of Sergipe, Lagarto CEP 49400-000, Brazil

4. Department of Pathology, Federal University of Santa Catarina, Florianópolis CEP 88040-370, Brazil

5. UCIBIO—Applied Molecular Biosciences Unit, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal

6. Associate Laboratory i4HB—Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal

7. Department of Pharmacy, Campus of Lagarto, Federal University of Sergipe, Lagarto CEP 49400-000, Brazil

Abstract

Medicinal plants have been commonly associated with chemotherapeutic treatments, as an approach to reduce the toxicological risks of classical anticancer drugs. The objective of this study was to evaluate the effects of combining the antineoplastic drug 5-fluorouracil (5-FU) with Matricaria recutita flowers extract (MRFE) to treat mice transplanted with sarcoma 180. Tumor inhibition, body and visceral mass variation, biochemical, hematological, and histopathological parameters were evaluated. The isolated 5-FU, 5-FU+MRFE 100 mg/kg/day, and 5-FU+MRFE 200 mg/kg/day reduced tumor growth; however, 5-FU+MRFE 200 mg/kg/day showed a more significant tumor reduction when compared to 5-FU alone. These results corroborated with the analysis of the tumor histopathological and immunodetection of the Ki67 antigen. In the toxicological analysis of the association 5-FU+MRFE 200 mg/kg/day, an intense loss of body mass was observed, possibly as a result of diarrhea. In addition, spleen atrophy, with a reduction in white pulp, leukopenia and thrombocytopenia, was observed in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day did not interfere in myelosuppressive action of 5-FU. In hematological analysis, body and visceral mass variation and biochemical parameters related to renal (urea and creatinine) and cardiac (CK-MB) function, no alteration was observed. In biochemical parameters related to liver function enzymes, there was a reduction in aspartate transaminase (AST) values in the 5-FU groups alone and associated with MRFE 200 mg/kg/day; however, there was no statistical difference between these groups. Therefore, the MRFE 200 mg/kg/day does not appear to influence enzyme reduction. The results of this study suggest that the association between the 5-FU+MRFE 200 can positively interfere with the antitumor activity, promoting the antineoplastic-induced reduction in body mass, while minimizing the toxicity of chemotherapy.

Funder

FAPITEC—Foundation for Research Support and Technological Innovation of the State of Sergipe

Publisher

MDPI AG

Subject

Chemical Health and Safety,Health, Toxicology and Mutagenesis,Toxicology

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