title: Diminazene aceturate liposomes: morphometric and biochemical liver, kidney, and spleen of rats infected with Trypanosoma evansi.
abstract: The aim of this study was to evaluate the effect of treatment with liposomal (L-DMZ) and conventional (C-DMZ) diminazene aceturate formulations on hepatic and renal functions of rats, experimentally infected with Trypanosoma evansi. For this purpose, 72 Wistar rats (Rattus norvegicus) were divided into six groups (A, B, C, D, E, and F). Each group was subdivided into two other subgroups in order to assess the biochemical and histological results on days 7 and 40 post-treatment (PT). Treatments were carried out based on two different therapeutic protocols: L-DMZ and C-DMZ at 3.5mg/kg(-1), single dose (groups C and D), and five successive doses within intervals of 24h (groups E and F). Groups A and B corresponded to uninfected and infected (without treatment) animals, respectively. Sample collections were held on days 7 and 40 PT for the assessment of hepatic [alkaline phosphatase (AP), alanine transferase (ALT), albumin, gamma glutamil transferase (GGT) and renal functions (creatinine and urea). Additionally, the histology of fragments of liver, kidney, and spleen was performed. Animals in group B showed a significant increase in AP, GGT, ALT, and urea when compared with group A. On day 7 post-inoculation (PI), the biochemical analysis showed a reduction (P<0.05) of AP and GGT, while the levels of urea were increased in groups C, D, E, F. On day 40 PT, ALT was increased in these same groups when compared with group A. In histopathology, changes in liver samples were observed on day 7 PT in groups D and F, especially regarding the area and density of the hepatocytes. Renal analysis exhibited changes in glomerular space, glomerular, and corpuscular areas in group E. Therefore, these results allowed us to conclude that the treatment with L-DMZ and C-DMZ led to variable biochemical changes, which defined the functions of the liver and kidneys of treated animals, since the main histopathology alterations were observed in animals treated with liposomes, at their higher dosages. Thus, treatments with L-DMZ and C-DMZ in five consecutive doses were effective although being followed by liver toxicity.
authors.affiliation: Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Brazil. Electronic address: camilabelmontevet@yahoo.com.br.
authors.forename: Camila Belmonte
authors.initials: CB
authors.lastname: Oliveira
authors.affiliation: Department of Production and Control of Medicines, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Lucas Almeida
authors.initials: LA
authors.lastname: Rigo
authors.affiliation: Department of Small Animal, Universidade Federal de Santa Maria, Brazil.
authors.forename: Raqueli T
authors.initials: RT
authors.lastname: França
authors.affiliation: Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Brazil.
authors.forename: Lucas T
authors.initials: LT
authors.lastname: Gressler
authors.affiliation: Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Dalla Rosa
authors.affiliation: Department of Production and Control of Medicines, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Aline F
authors.initials: AF
authors.lastname: Ourique
authors.affiliation: Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Brazil.
authors.forename: Dionatan T
authors.initials: DT
authors.lastname: Oliveira
authors.affiliation: Department of Small Animal, Universidade Federal de Santa Maria, Brazil.
authors.forename: Rovaina L
authors.initials: RL
authors.lastname: Doyle
authors.affiliation: Departamento of Morphology and Histology, Universidade Federal de Santa Maria, Brazil.
authors.forename: Karen Luise dos Santos
authors.initials: KL
authors.lastname: Moreira
authors.affiliation: Departamento of Morphology and Histology, Universidade Federal de Santa Maria, Brazil.
authors.forename: Marcelo L
authors.initials: ML
authors.lastname: Veiga
authors.affiliation: Department of Small Animal, Universidade Federal de Santa Maria, Brazil.
authors.forename: Sonia T A
authors.initials: ST
authors.lastname: Lopes
authors.affiliation: Department of Production and Control of Medicines, Faculty of Pharmacy, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Ruy Carlos R
authors.initials: RC
authors.lastname: Beck
authors.affiliation: Department of Animal Science, Universidade do Estado de Santa Catarina, Chapecó, Brazil.
authors.forename: Aleksandro S
authors.initials: AS
authors.lastname: Da Silva
authors.affiliation: Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Brazil. Electronic address: sgmonteiro@uol.com.br.
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Monteiro
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D004133:Diminazene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D004195:Disease Models, Animal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D008081:Liposomes; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D014345:Trypanosoma / Q000187:drug effects* / Q000472:pathogenicity; D014352:Trypanosomiasis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology
chemical_list: D015415:Biomarkers; D008081:Liposomes; D014344:Trypanocidal Agents; C003915:diminazene aceturate; D004133:Diminazene
keywords: Diamidines; Lipid vesicles; Toxicity