Protective effect of β-glucan and glutamine on intestinal and immunological damage in mice induced by cytarabine (Ara-C)

Recently, glutamine and β-glucan have been demonstrated to play an important role in modulation of the immune system and in promoting intestinal health benefits. The aim of this study was to investigate the effect of this intervention on inflammatory responses and intestinal health in mice orally pretreated with soluble Saccharomyces cerevisiae derived 1,3/1,6-β-glucan (80mg/kg) with or without glutamine (150mg/kg) and then challenged with cytarabine (Ara-C) (15mg/kg). Improvements in villi and crypts were not observed in the β-glucan group. The intestinal morphometry in the glutamine group showed the best results. β-glucan in combination with glutamine presented the highest values of IL-1β and IL-10 and lowest values for leukocytes and INF-γ. Based on these results, combined β-glucan and glutamine pretreatment reduced intestinal inflammation and improved the immune response after Ara-C challenge.

INDEX TERMS:
β-glucan; glutamine; intestine; immunology; mice; cytarabine; Ara-C; chemotherapy; yeast; intestinal health; immunomodulators

Authorship

Mariana Y.H. Porsani ^**Corresponding author: mariporsani@hotmail.com

Departamento de Clínica Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, Cidade Universitária, Av. Prof. Dr. Orlando Marques de Paiva 87, São Paulo, SP 05508-270, Brazil.Universidade de São PauloBrazilSão Paulo, SP, Brazil Departamento de Clínica Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, Cidade Universitária, Av. Prof. Dr. Orlando Marques de Paiva 87, São Paulo, SP 05508-270, Brazil.

Monique Paludetti

Laboratório de Fisiologia Veterinária, Departamento de Medicina Veterinária, Universidade Federal de Lavras (UFLA), Campus Universitário, Av. Doutor Sylvio Menicucci 1001, Kennedy, Lavras, MG 37200-000, Brazil. E-mail: moniiiique@gmail.comUniversidade Federal de LavrasBrazilLavras, MG, BrazilLaboratório de Fisiologia Veterinária, Departamento de Medicina Veterinária, Universidade Federal de Lavras (UFLA), Campus Universitário, Av. Doutor Sylvio Menicucci 1001, Kennedy, Lavras, MG 37200-000, Brazil. E-mail: moniiiique@gmail.com

Débora R. Orlando

Laboratório de Patologia Veterinária, Departamento de Medina Veterinária, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Av. Universitária, Unaí, MG 38610-000, Brazil. E-mail: deboraribeiro.orlando@gmail.comUniversidade Federal dos Vales do Jequitinhonha e MucuriBrazilUnaí, MG, Brazil Laboratório de Patologia Veterinária, Departamento de Medina Veterinária, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Av. Universitária, Unaí, MG 38610-000, Brazil. E-mail: deboraribeiro.orlando@gmail.com

Ana P. Peconick

Laboratório de Biologia Parasitológica, Departamento de Medicina Veterinária, UFLA, Campus Universitário, Av. Doutor Sylvio Menicucci 1001, Kennedy, Lavras, MG 37200-000, Brazil. E-mail: anappeconick@dmv.ufla.brUFLABrazilLavras, MG, BrazilLaboratório de Biologia Parasitológica, Departamento de Medicina Veterinária, UFLA, Campus Universitário, Av. Doutor Sylvio Menicucci 1001, Kennedy, Lavras, MG 37200-000, Brazil. E-mail: anappeconick@dmv.ufla.br

Rafael C. Costa

Laboratório de Patologia Veterinária, Departamento de Medicina Veterinária, UFLA, Campus Universitário, Av. Doutor Sylvio Menicucci 1001, Kennedy, Lavras, MG 37200-000, Brazil. E-mail: rafaelccosta3@gmail.comUFLABrazilLavras, MG, BrazilLaboratório de Patologia Veterinária, Departamento de Medicina Veterinária, UFLA, Campus Universitário, Av. Doutor Sylvio Menicucci 1001, Kennedy, Lavras, MG 37200-000, Brazil. E-mail: rafaelccosta3@gmail.com

Luiz E.D. Oliveira

Márcio G. Zangeronimo

Raimundo V. Sousa

*Corresponding author: mariporsani@hotmail.com

Conflict of interest.- The authors report no conflicts of interest.

SCIMAGO INSTITUTIONS RANKINGS

Figures

Figures (5)

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Fig.1.
Histological section of duodenum of mice used in the present study. HE. Note that histologically there are no changes in the morphology of histological sections among the groups. (A) Control group- (Mice without any treatment). (B) Ara-C group- (Mice challenged with Ara-C), (C) β- Glucan group-(Mice treated with β-Glucan and challenged with Ara-C). (D) Glutamine group- (Mice treated with Glutamine and challenged with Ara- C). (E) β- Glucan and Glutamine group- (Mice treated with β- Glucan in association with Glutamine and challenged with Ara-C).

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Fig.2.
Morphometry of duodenum of mice in control group. During the morphometric studies, villi height and width and crypt depth and width were measured in all the segments of the small intestine (duodenum, jejunum and ileum) of all animals. (A) Villi height mensuration. (B) Crypt depth mensuration. (C) Villi width mensuration. (D) Crypt 4 width mensuration.

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Fig.3.
(A) Total of leukocytes of mice treated with or without β- Glucan and Glutamine prior to challenge with Ara-C. (B) Mean standard of IL-10 (pg/ml), IL 1-β (pg/ml) and INF-γ (pg/ml) of mice treated with or without β- Glucan and Glutamine prior to challenge with Ara-C.

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Fig.4.
(A) Mean ± standard deviation of morphometry of the villi of the duodenum of the ileum of mice treated with or without of β- Glucan and Glutamine mice prior to challenge with Ara-C. (B) Crypts of the ileum of mice treated with or without of β- Glucan and Glutamine mice prior to challenge with Ara-C.

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Fig.5.
Immunohistochemistry (avidin-biotin) of B-Lymphocyte, T-Lymphocyte in ileum of mice and Macrophage in ileum of mice. Note the marking (brownish color) of lymphocytes in the interstitial region of the different groups: (A) B-Lymphocyte in ileum of mice of Control group. (B) B-Lymphocyte in ileum of mice of Ara-C group. (C) B-Lymphocyte in ileum of mice of β- Glucan group. (D) B-Lymphocyte in ileum of mice of Glutamine group. (E) B-Lymphocyte in ileum of mice of β- Glucan and Glutamine group. (F) T-Lymphocyte in ileum of mice of Control group. (G) T-Lymphocyte in ileum of mice of Ara-C group. (H) T-Lymphocyte in ileum of mice of β- Glucan group. (I) T-Lymphocyte in ileum of mice of Glutamine group. (J) Lymphocyte in ileum of mice of β-Glucan and Glutamine group. (G) Macrophage in ileum of mice of Control group. (H) Macrophage in ileum of mice of Ara-C group, there are a few marked cells. (I) Macrophage in ileum of mice of Ara-C group β- Glucan Group. (J) Glutamine group. (K) Macrophage in ileum of mice of Ara-C group β- Glucan and Glutamine group.

Fig.1. Histological section of duodenum of mice used in the present study. HE. Note that histologically there are no changes in the morphology of histological sections among the groups. (A) Control group- (Mice without any treatment). (B) Ara-C group- (Mice challenged with Ara-C), (C) β- Glucan group-(Mice treated with β-Glucan and challenged with Ara-C). (D) Glutamine group- (Mice treated with Glutamine and challenged with Ara- C). (E) β- Glucan and Glutamine group- (Mice treated with β- Glucan in association with Glutamine and challenged with Ara-C).

Fig.2. Morphometry of duodenum of mice in control group. During the morphometric studies, villi height and width and crypt depth and width were measured in all the segments of the small intestine (duodenum, jejunum and ileum) of all animals. (A) Villi height mensuration. (B) Crypt depth mensuration. (C) Villi width mensuration. (D) Crypt 4 width mensuration.

Fig.3. (A) Total of leukocytes of mice treated with or without β- Glucan and Glutamine prior to challenge with Ara-C. (B) Mean standard of IL-10 (pg/ml), IL 1-β (pg/ml) and INF-γ (pg/ml) of mice treated with or without β- Glucan and Glutamine prior to challenge with Ara-C.

Fig.4. (A) Mean ± standard deviation of morphometry of the villi of the duodenum of the ileum of mice treated with or without of β- Glucan and Glutamine mice prior to challenge with Ara-C. (B) Crypts of the ileum of mice treated with or without of β- Glucan and Glutamine mice prior to challenge with Ara-C.

Fig.5. Immunohistochemistry (avidin-biotin) of B-Lymphocyte, T-Lymphocyte in ileum of mice and Macrophage in ileum of mice. Note the marking (brownish color) of lymphocytes in the interstitial region of the different groups: (A) B-Lymphocyte in ileum of mice of Control group. (B) B-Lymphocyte in ileum of mice of Ara-C group. (C) B-Lymphocyte in ileum of mice of β- Glucan group. (D) B-Lymphocyte in ileum of mice of Glutamine group. (E) B-Lymphocyte in ileum of mice of β- Glucan and Glutamine group. (F) T-Lymphocyte in ileum of mice of Control group. (G) T-Lymphocyte in ileum of mice of Ara-C group. (H) T-Lymphocyte in ileum of mice of β- Glucan group. (I) T-Lymphocyte in ileum of mice of Glutamine group. (J) Lymphocyte in ileum of mice of β-Glucan and Glutamine group. (G) Macrophage in ileum of mice of Control group. (H) Macrophage in ileum of mice of Ara-C group, there are a few marked cells. (I) Macrophage in ileum of mice of Ara-C group β- Glucan Group. (J) Glutamine group. (K) Macrophage in ileum of mice of Ara-C group β- Glucan and Glutamine group.

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Protective effect of β-glucan and glutamine on intestinal and immunological damage in mice induced by cytarabine (Ara-C)

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[1] *Corresponding author: mariporsani@hotmail.com