Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: an experimental study / Avaliação dos efeitos de sugamadex e dexmedetomidina intra-arterial: estudo experimental

Abstract Background: Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. Methods: Rabbits were randomly divided into 4 groups. Group Control (n = 7); no intervention performed. Group Catheter (n = 7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n = 7); rabbits were given 4 mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n = 7); rabbits were given 1 µg/kg dexmedetomidine into the central artery of the ear. After 72 h, the ears were amputated and histologically investigated. Results: There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p < 0.05). There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores. Conclusion: Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed.

Resumo Justificativa: A injeção intra-arterial de medicamentos pode causar isquemia aguda e grave e resultar em morbidade e mortalidade. Não há informações na literatura que avaliem os efeitos endoteliais arteriais de sugamadex e dexmedetomidina. A hipótese de nosso estudo foi que dexmedetomidina e sugamadex causariam alterações histológicas na estrutura endotelial arterial quando administrados por via intra-arterial. Método: Os coelhos foram randomicamente divididos em quatro grupos: grupo controle (n = 7), sem intervenção; grupo cateter (n = 7), uma cânula foi inserida na artéria central da orelha e medicamentos não foram administrados; grupo sugamadex (n = 7), receberam 4 mg/kg de sugamadex na artéria central da orelha; grupo dexmedetomidina (n = 7), receberam 1 µg/kg de dexmedetomidina na artéria central da orelha. Após 72 horas, as orelhas foram amputadas e histologicamente examinadas. Resultados: Não houve diferença significativa entre os grupos controle e cateter referente aos escores histológicos. Os escores do dano causado ao endotélio e à membrana e fibra elásticas, da hipertrofia do músculo liso e do aumento do tecido conjuntivo foram significativamente maiores nos grupos dexmedetomidina e sugamadex do que nos grupos controle e cateter (p < 0,05). Não houve diferença significativa entre os grupos dexmedetomidina e sugamadex nos escores histológicos. Conclusão: A administração de sugamadex e dexmedetomidina a coelhos por via intra-arterial causou danos arteriais histológicos. Para entender as alterações histológicas causadas por sugamadex e dexmedetomidina com mais clareza, estudos experimentais adicionais são necessários.

Capparis ovata treatment suppresses inflammatory cytokine expression and ameliorates experimental allergic encephalomyelitis model of multiple sclerosis in C57BL/6 mice.

Since ancient times, Capparis species have been widely used in traditional medicine to treat various diseases. Our recent investigations have suggested Capparis ovata's potential anti-neuroinflammatory application for the treatment of multiple sclerosis (MS). The present study was designed to precisely determine the underlying mechanism of its anti-neuroinflammatory effect in a mouse model of MS. C. ovata water extract (COWE) was prepared using the plant's fruit, buds, and flower parts (Turkish Patent Institute, PT 2012/04,093). We immunized female C57BL/6J mice with MOG35-55/CFA. COWE was administered at a daily dose of 500mg/kg by oral gavage either from the day of immunization (T1) or at disease onset (T2) for 21days. Gene expression analysis was performed using a Mouse Multiple Sclerosis RT² Profiler PCR Array, and further determinations and validations of the identified genes were performed using qPCR. Whole-genome transcriptome profiling was analyzed using Agilent SurePrint G3 Mouse GE 8X60K microarrays. Immunohistochemical staining was applied to brain sections of the control and treated mice to examine the degree of degeneration. COWE was further fractionated and analyzed phytochemically using the Zivak Tandem Gold Triple Quadrupole LC/MS-MS system. COWE remarkably suppressed the development of EAE in T1, and the disease activity was completely inhibited. In the T2 group, the maximal score was significantly reduced compared with that of the parallel EAE group. The COWE suppression of EAE was associated with a significantly decreased expression of genes that are important in inflammatory signaling, such as TNFα, IL6, NF-κB, CCL5, CXCL9, and CXCK10. On the other hand, the expression of genes involved in myelination/remyelination was significantly increased. Immunohistochemical analysis further supported these effects, showing that the number of infiltrating immune cells was decreased in the brains of COWE-treated animals. In addition, differential expression profiling of the transcriptome revealed that COWE treatment caused the down regulation of a group of genes involved in the immune response, inflammatory response, antigen processing and presentation, B-cell-mediated immunity and innate immune response. Collectively, these results suggest anti-neuroinflammatory mechanisms by which COWE treatment delayed and suppressed the development of EAE and ameliorated the disease in mice with persistent clinical signs.

Effect of induced hypothermia on lipopolysaccharide-induced lung injury in neonatal rats.

OBJECTIVES: Recent data suggest that induced hypothermia has some protective effects on experimental lung injury. We aimed to evaluate the protective effect of mild hypothermia in a rat model of lipopolysaccharide (LPS) induced neonatal lung injury. METHODS: Wistar rat pups were divided into four groups, specifically: (i) A control group, with no LPS administration and maintained in room air; (ii) A LPS group, with antenatal LPS administrated and maintained in room air; (iii) A LPS + hypothermia group, with antenatal LPS administrated and exposed to hypothermia; (iv) A hypothermia group, with no LPS administration and exposed to hypothermia. Intraperitoneal LPS was injected into maternal rats at the 19th and 20th gestational days to establish a neonatal lung injury model. Mild hypothermia was started at the postnatal 24th hour and continued during 24 h. At the postnatal 7th day, the rats were sacrificed and lung samples were evaluated for immunohistochemical tests and proinflammatory gene expression levels. RESULTS: Hypothermia therapy attenuated the damaging effects of antenatal LPS administration. Furthermore, hypothermia therapy reduced gene expression of pro-inflammatory cytokines (IL-6, IL-1α, IL-1ß, TNF-α) and induced the expression of a potent anti-inflammatory cytokine (IL-10). CONCLUSION: The results of this study indicated that mild hypothermia therapy is effective in an LPS induced neonatal lung injury model. If these results are supported by further studies, hypothermia may also be a new therapy option for preventing bronchopulmonary dysplasia.