Creolina <sup>®</sup> administrada por diferentes vias em ratos envenenados experimentalmente com veneno de Bothrops jararaca

Carvalho, Lucas Rannier Ribeiro Antonino; Pereira, Helder Camilo da Silva; Silva, Hugo Thyares Fonseca Nascimento Pereira da; Lucena, Ricardo Barbosa de; Guerra, Ricardo Romão

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PATHOLOGY • Cienc. Rural 49 (5) • 2019 • https://doi.org/10.1590/0103-8478cr20180699 copiar

Creolina ^® administrada por diferentes vias em ratos envenenados experimentalmente com veneno de Bothrops jararaca

Autoria SCIMAGO INSTITUTIONS RANKINGS

RESUMO:

Esse estudo objetivou avaliar os efeitos da Creolina^® quando administrada por diferentes vias de acesso em ratos experimentalmente envenenados pela peçonha de Bothrops jararaca. Em ratas Wistar fêmeas foi inoculada a peçonha botrópica por via intramuscular, e em seguida as ratas foram tratadas com Creolina^® (administrada oralmente, topicamente e intramuscularmente) ou a mistura de veneno + Creolina^®. Os animais que receberam a Creolina^®, além do veneno, por via oral, tópica e muscular desenvolveram a sintomatologia local e achados laboratoriais semelhantes ao grupo que recebeu apenas o veneno. De forma controversa, os animais inoculados com o veneno misturado a Creolina^® não apresentaram sinais característicos da ação local do veneno (necrose, hemorragia) e apresentaram parâmetros hematológicos dentro da normalidade para espécie. Esses resultados sugerem que a Creolina^® apresentou efeito antiofídico apenas quando misturada ao veneno e administrada intramuscularmente.

Palavras-chave:
antiveneno; medicina popular; veneno botrópico

Autoria

Lucas Rannier Ribeiro Antonino Carvalho

Programa de Pós-graduação em Ciência Animal, Universidade Federal da Paraíba (UFPB), Areia, PB, Brasil.Universidade Federal da Paraíba (UFPB)BrazilAreia, PB, BrazilPrograma de Pós-graduação em Ciência Animal, Universidade Federal da Paraíba (UFPB), Areia, PB, Brasil.

http://orcid.org/0000-0002-5875-8573

Helder Camilo da Silva Pereira

Universidade Federal da Paraíba (UFPB), Curso de Medicina Veterinária, Areia, PB, Brasil.Universidade Federal da Paraíba (UFPB),BrazilAreia, PB, BrazilUniversidade Federal da Paraíba (UFPB), Curso de Medicina Veterinária, Areia, PB, Brasil.

http://orcid.org/0000-0001-9265-8966

Hugo Thyares Fonseca Nascimento Pereira da Silva

Ricardo Barbosa de Lucena

Programa de Pós-graduação em Ciência Animal, Universidade Federal da Paraíba (UFPB), 58397-000, Areia, PB, Brasil. Universidade Federal da Paraíba (UFPB)BrazilAreia, PB, BrazilPrograma de Pós-graduação em Ciência Animal, Universidade Federal da Paraíba (UFPB), 58397-000, Areia, PB, Brasil.

http://orcid.org/0000-0003-1162-1948

Ricardo Romão Guerra ^*E-mail: ricardo@cca.ufpb.br. *Corresponding author.

http://orcid.org/0000-0001-8226-8606

E-mail: ricardo@cca.ufpb.br. ^*Corresponding author.

DECLARATION OF CONFLICT OF INTERESTS

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

AUTHORS’ CONTRIBUTIONS

All authors contributed equally for the conception and writing of the manuscript. All authors critically revised the manuscript and approved of the final version.

SCIMAGO INSTITUTIONS RANKINGS

Figuras | Tabelas

Figuras (1)
Tabelas (3)

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Figure 1
Macroscopic and microscopic evaluation of the right hind limbs of Wistar rats after experimental bothropic poisoning (Bothrops jararaca) and treatment with Creolin^®. A1) Photographic image of the right-side face of the limb inoculated only with Creolin^® intramuscularly. A2) Photomicrography of the inoculation region of Creolin^® with evident neutrophil infiltrate (^*). Hematoxylin-Eosin staining. Bar: 200 micrometers. B1) Photographic image of the right-side face of the limb inoculated only with bothropic poison intramuscularly presenting friable appearance, edema, and hemorrhage. B2) Photomicrography of the venom inoculation region with diffuse hemorrhage (arrows). Hematoxylin-Eosin staining. Bar: 100 micrometers. C1) Photographic image of the right-side face of the limb inoculated with bothropic venom and then Creolin^® intramuscularly, presenting friable appearance, edema, and hemorrhage similar to inoculation only with the venom. C2) Photomicrography of the venom inoculation region and the Creolin^® injected intramuscularly with diffuse hemorrhage (arrows). Hematoxylin-Eosin staining. Bar: 200 micrometers. D1) Photographic image of the right-side face of the limb inoculated with the venom + Creolin^® mixture intramuscularly. D2) Photomicrography of the inoculation region of the venom + Creolin^® mixture injected intramuscularly with the presence of neutrophil infiltrate (^*). Hematoxylin-eosin staining. Bar: 100 micrometers.

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Table 1
Identified changes and their time intervals in a group of Wistar rats after experimental bothropic poisoning (Bothrops jararaca) and treatment with Creolin^® by different access routes.

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Table 2
Renal and muscular histopathological changes in Wistar rats after experimental bothropic poisoning (Bothrops jararaca) and treatment with Creolin^® by different access routes after eight hours of inoculation.

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Table 3
Hematological values of Wistar rats, eight hours after experimental bothropic poisoning (Bothrops jararaca) and treatment with Creolin^® by different access routes (^*). Values expressed as mean ± standard deviation.

Figure 1 Macroscopic and microscopic evaluation of the right hind limbs of Wistar rats after experimental bothropic poisoning (Bothrops jararaca) and treatment with Creolin^®. A1) Photographic image of the right-side face of the limb inoculated only with Creolin^® intramuscularly. A2) Photomicrography of the inoculation region of Creolin^® with evident neutrophil infiltrate (^). Hematoxylin-Eosin staining. Bar: 200 micrometers. B1) Photographic image of the right-side face of the limb inoculated only with bothropic poison intramuscularly presenting friable appearance, edema, and hemorrhage. B2) Photomicrography of the venom inoculation region with diffuse hemorrhage (arrows). Hematoxylin-Eosin staining. Bar: 100 micrometers. C1) Photographic image of the right-side face of the limb inoculated with bothropic venom and then Creolin^® intramuscularly, presenting friable appearance, edema, and hemorrhage similar to inoculation only with the venom. C2) Photomicrography of the venom inoculation region and the Creolin^® injected intramuscularly with diffuse hemorrhage (arrows). Hematoxylin-Eosin staining. Bar: 200 micrometers. D1) Photographic image of the right-side face of the limb inoculated with the venom + Creolin^® mixture intramuscularly. D2) Photomicrography of the inoculation region of the venom + Creolin^® mixture injected intramuscularly with the presence of neutrophil infiltrate (^). Hematoxylin-eosin staining. Bar: 100 micrometers.

Table 1 Identified changes and their time intervals in a group of Wistar rats after experimental bothropic poisoning (Bothrops jararaca) and treatment with Creolin^® by different access routes.

Changes	Control	imC	Bj	Bj+voC	Bj+vtC	Bj+imC	imBj+C
Claudication	Absent	0 h-3 h	0 h-8 h	0 h-8 h	0 h-8 h	0 h-8 h	0 h-8 h
Prostration	Absent	Absent	0 h-5 h	0 h-4 h	0 h-3 h	0 h-4 h	0 h-4 h
Myoclonus	Absent	Absent	Absent	0 h-2 h	0 h-2 h	Absent	0 h-2 h
Bleeding	Absent	Absent	1 h-8 h	2 h-8 h	2 h-8 h	01-8 h	Absent
Pain	0 h-1 h	0 h-2 h	0 h-8 h	0 h-8 h	0 h-8 h	0 h-8 h	0 h-8 h
Dark urine	Absent	Absent	1 h-8 h	2 h-5 h	2 h-5 h	2 h-5 h	2 h-3 h
Anorexia	0 h-1 h	0 h-3 h	0 h-5 h	0 h-5 h	0 h-3 h	0 h-4 h	0 h-5 h
Death	0/5	0/5	0/5	0/5	2/5	0/5	0/5

Control: sterile saline solution; Bj: only intramuscular bothropic venom; imC: only intramuscular Creolin^®; Bj+voC: bothropic venom followed by oral Creolin^® treatment; Bj+vtC: bothropic venom followed by topical Creolin^® treatment; Bj+imC: bothropic venom and followed by intramuscular injection of Creolin^®; imBj+C:intramuscular injection of a mixture of Creolin^® and bothropic venom.

Table 2 Renal and muscular histopathological changes in Wistar rats after experimental bothropic poisoning (Bothrops jararaca) and treatment with Creolin^® by different access routes after eight hours of inoculation.

Renal Changes	Control	imC	Bj	Bj+voC	Bj+vtC	Bj+imC	imBj+C
Granular cylinders	-	-	+++	+++	+++	+++	++
Hyaline cylinders	-	-	++	+++	+++	+++	+
Hydropic degeneration	-	-	+	+	+	+	-
Necrosis of tubules	-	-	++	+	-	+	-
Muscular Changes	Control	imC	Bj	Bj+voC	Bj+vtC	Bj+imC	imBj+C
Bleeding	-	-	+++	+++	+++	++	-
Edema	-	++	+++	+++	++	++	+
Neutrophilic infiltrate	-	+++	-	-	++	+	+++
Hyaline degeneration	-	-	+	+	-	+	-

Control: sterile saline solution; Bj: only intramuscular bothropic venom; imC: only intramuscular Creolin^®; Bj+voC: bothropic venom followed by oral Creolin^® treatment; Bj+vtC: bothropic venom followed by topical Creolin^® treatment; Bj+imC: bothropic venom and followed by intramuscular injection of Creolin^®; imBj+C:intramuscular injection ofa mixture of Creolin^® and bothropic venom.

Table 3 Hematological values of Wistar rats, eight hours after experimental bothropic poisoning (Bothrops jararaca) and treatment with Creolin^® by different access routes (^*). Values expressed as mean ± standard deviation.

Hemogram	Control (n=5)	imC (n=4)	Bj (n=5)	Bj+voC (n=4)	Bj+vtC (n=3)	Bj+imC (n=5)	imBj+C (n=4)
Leukocytes (x10³/μL)	5.2±0.9b	7.8±1.7ab	9.5±1.3a	6.9±0.7ab	5.2±0.9b	7.3±2.3ab	6.2±0.2b
Blood Cells (x10⁶/μL)	7.2±0.4ab	7.5±0.7a	6.6±0.5abc	4.6±0.4d	4.9±0.2d	6.0±0.3c	6.3±0.2bc
Hemoglobin (g/dL)	15.2±1.0a	15.8±0.5a	13.4±1.0b	9.5±0.9c	9.2±0.4c	12.2±0.6b	13.1±0.3b
Hematocrit (%)	42.0±2.6ab	45.2±1.2a	37.3±2.6c	26.7±3.0d	28.1±0.2d	34.1±1.8c	38.0±1.0bc
Plasma Protein (g/dL)	6.4±0.2a	6.7±0.3a	5.2±0.3c	5.6±0.1bc	5.3±0.3bc	5.2±0.3c	6.0±0.1ab
Fibrinogen (mg/dL)	225.0±125.8a	225.0±50.0a	100.0±89.4a	100.0±115.5a	66.6±115.5a	140.0±260.8a	160.0±167.3a
Platelets (10³/µL)	704.3±135.3a	840.5±82.1a	13.6±6.9b	77.2±61.7b	88.3±31.3b	11.0±4.0b	838.0±209.6a

^*Mean in the same line, followed by distinct letters differed by Tukey test and p<0.05. Control: sterile saline solution; Bj: only intramuscular bothropic venom; imC: only intramuscular Creolin^®; Bj+voC: bothropic venom followed by oral Creolin^® treatment; Bj+vtC: bothropic venom followed by topical Creolin^® treatment; Bj+imC: bothropic venom and followed by intramuscular injection of Creolin^®; imBj+C: intramuscular injection of a mixture of Creolin^® and bothropic venom.

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