RESUMO
Inflammatory bowel diseases (IBDs) are complex affections with increasing incidence worldwide. Multiple factors are involved in the development and maintenance of the symptoms including enhanced oxidative stress in intestinal mucosa. The conventional therapeutic approaches for IBDs are based on the use anti-inflammatory drugs with important collateral effects and partial efficacy. In the present work we tested the anti-inflammatory capacity of Kluyveromyces marxianus CIDCA 8154 in different models. In vitro, we showed that the pretreatment of epithelial cells with the yeast reduce the levels of intracellular reactive oxygen species. Furthermore, in a murine model of trinitro benzene sulfonic acid-induced colitis, yeast-treated animals showed a reduced histopathological score (P<0.05) and lower levels of circulating interleukin 6 (P<0.05). The capacity to modulate oxidative stress in vivo was assessed using a Caenorhabditis elegans model. The yeast was able to protect the nematodes from oxidative stress by modulating the SKN-1 transcription factor trough the DAF-2 pathway. These results indicate that K. marxianus CIDCA 8154 could control the intestinal inflammation and cellular oxidative stress. Deciphering the mechanisms of action of different probiotics might be useful for the rational formulation of polymicrobial products containing microorganisms targeting different anti-inflammatory pathways.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Colite/prevenção & controle , Kluyveromyces , Estresse Oxidativo , Probióticos/farmacologia , Animais , Células CACO-2 , Caenorhabditis elegans , Células HT29 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismoRESUMO
The intestine is highly sensitive to ischemia-reperfusion injury (IRI), a phenomenon occurring in different intestinal diseases. Several strategies to mitigate IRI are in experimental stages; unfortunately, no consensus has been reached about the most appropriate one. We report a protocol to study ischemic preconditioning (IPC) evaluation in mice and to combine IPC and tacrolimus (TAC) pretreatment in a warm ischemia model. Mice were divided into treated (IPC, TAC, and IPC + TAC) and untreated groups before intestinal ischemia. IPC, TAC, and IPC + TAC groups were able to decrease postreperfusion nitrites levels (P < .05). IPC-containing groups had a major beneficial effect by preserving the integrity of the intestinal histology (P < .05) and improving animal survival (P < .002) compared with TAC alone or the untreated group. The IPC + TAC group was the only one that showed significant improvement in lung histological analysis (P < .05). The TAC and IPC + TAC groups down-regulated intestinal expression of interleukin (II)-6 and IL1b more than 10-fold compared with the control group. Although IPC and TAC alone reduced intestinal IRI, the used of a combined therapy produced the most significant results in all the local and distant evaluated parameters.
Assuntos
Imunossupressores/farmacologia , Enteropatias/prevenção & controle , Intestinos/efeitos dos fármacos , Precondicionamento Isquêmico , Traumatismo por Reperfusão/prevenção & controle , Tacrolimo/farmacologia , Animais , Biomarcadores/metabolismo , Terapia Combinada , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Enteropatias/etiologia , Enteropatias/metabolismo , Enteropatias/patologia , Mucosa Intestinal/metabolismo , Intestinos/irrigação sanguínea , Intestinos/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nitritos/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fatores de Tempo , Isquemia Quente/efeitos adversosRESUMO
Among the abdominal organs, the intestine is probably the most sensitive to ischemia reperfusion injury (IRI), a phenomenon that occurs in many intestinal disorders. Few studies have reported in detail the impact of intestinal ischemia time in mice. We evaluated the effect of various warm intestinal ischemia times in an intestinal IRI model in mice. Adult male Balb/c mice were divided into 4 groups that differed in intestinal ischemia time: G1, 30; minutes; G2, 35 minutes; G3, 40 minutes; and G4, 45 minutes. Histological evaluation showed average Park scores as follows: G1 0.6 ± 0.55; G2 1.8 ± 0.45; G3 4.8 ± 2.25; and G4 5 ± 1.79. All animals from G1 survived 30 hours. G2 animals showed intermediate behavior with all succumbing between 18 and 30 hours postprocedure. G3 and G4 displayed similar survival results with animals succumbing before 6 hours after intestinal reperfusion. These data showed that Park index scores of 3 or higher were related to early death. We concluded that the 5 minutes between 35 and 40 minutes is the critical limit, after which all mice die after reperfusion. This result may represent a valuable tool for future research in mice.