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      Action of vanillin ( Vanilla planifolia) on the morphology of tibialis anterior and soleus muscles after nerve injury Translated title: Ação da vanilina ( Vanilla planifolia) sobre a morfologia dos músculos tibial anterior e sóleo após lesão nervosa

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          ABSTRACT

          Objective

          To evaluate the action of vanillin ( Vanilla planifolia) on the morphology of tibialis anterior and soleus muscles after peripheral nerve injury.

          Methods

          Wistar rats were divided into four groups, with seven animals each: Control Group, Vanillin Group, Injury Group, and Injury + Vanillin Group. The Injury Group and the Injury + Vanillin Group animals were submitted to nerve injury by compression of the sciatic nerve; the Vanillin Group and Injury + Vanillin Group, were treated daily with oral doses of vanillin (150mg/kg) from the 3rd to the 21st day after induction of nerve injury. At the end of the experiment, the tibialis anterior and soleus muscles were dissected and processed for light microscopy and submitted to morphological analysis.

          Results

          The nerve compression promoted morphological changes, typical of denervation, and the treatment with vanillin was responsible for different responses in the studied muscles. For the tibialis anterior, there was an increase in the number of satellite cells, central nuclei and fiber atrophy, as well as fascicular disorganization. In the soleus, only increased vascularization was observed, with no exacerbation of the morphological alterations in the fibers.

          Conclusion

          The treatment with vanillin promoted increase in intramuscular vascularization for the muscles studied, with pro-inflammatory potential for tibialis anterior, but not for soleus muscle.

          RESUMO

          Objetivo

          Avaliar a ação da vanilina ( Vanilla planifolia) sobre a morfologia dos músculos tibial anterior e sóleo após lesão nervosa periférica.

          Métodos

          Ratos Wistar foram divididos em quatro grupos, com sete animais cada, sendo Grupo Controle, Grupo Vanilina, Grupo Lesão e Grupo Lesão + Vanilina. Os animais dos Grupos Lesão e Grupo Lesão + Vanilina foram submetidos à lesão nervosa por meio da compressão do nervo isquiático, e os Grupos Vanilina e Grupo Lesão + Vanilina foram tratados diariamente com doses orais de vanilina (150mg/kg) do 3 o ao 21 o dia após a indução da lesão nervosa. Ao término do experimento, os músculos tibial anterior e sóleo foram dissecados e seguiram o processamento de rotina em microscopia de luz, para posterior análise morfológica.

          Resultados

          A compressão nervosa promoveu alterações morfológicas características de denervação, sendo que o tratamento com vanilina foi responsável por respostas distintas nos músculos estudados. Para o tibial anterior, houve aumento do número de células satélites, núcleos centrais e atrofia das fibras, bem como desorganização fascicular. Já no sóleo, houve apenas aumento da vascularização, sem exacerbação das alterações morfológicas nas fibras.

          Conclusão

          O tratamento com vanilina promoveu o aumento da vascularização intramuscular para os músculos estudados, com potencial pró-inflamatório para o tibial anterior, o que não ocorreu no músculo sóleo.

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          Most cited references33

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          Inflammatory processes in muscle injury and repair.

          Modified muscle use or injury can produce a stereotypic inflammatory response in which neutrophils rapidly invade, followed by macrophages. This inflammatory response coincides with muscle repair, regeneration, and growth, which involve activation and proliferation of satellite cells, followed by their terminal differentiation. Recent investigations have begun to explore the relationship between inflammatory cell functions and skeletal muscle injury and repair by using genetically modified animal models, antibody depletions of specific inflammatory cell populations, or expression profiling of inflamed muscle after injury. These studies have contributed to a complex picture in which inflammatory cells promote both injury and repair, through the combined actions of free radicals, growth factors, and chemokines. In this review, recent discoveries concerning the interactions between skeletal muscle and inflammatory cells are presented. New findings clearly show a role for neutrophils in promoting muscle damage soon after muscle injury or modified use. No direct evidence is yet available to show that neutrophils play a beneficial role in muscle repair or regeneration. Macrophages have also been shown capable of promoting muscle damage in vivo and in vitro through the release of free radicals, although other findings indicate that they may also play a role in muscle repair and regeneration through growth factors and cytokine-mediated signaling. However, this role for macrophages in muscle regeneration is still not definitive; other cells present in muscle can also produce the potentially regenerative factors, and it remains to be proven whether macrophage-derived factors are essential for muscle repair or regeneration in vivo. New evidence also shows that muscle cells can release positive and negative regulators of inflammatory cell invasion, and thereby play an active role in modulating the inflammatory process. In particular, muscle-derived nitric oxide can inhibit inflammatory cell invasion of healthy muscle and protect muscle from lysis by inflammatory cells in vivo and in vitro. On the other hand, muscle-derived cytokines can signal for inflammatory cell invasion, at least in vitro. The immediate challenge for advancing our current understanding of the relationships between muscle and inflammatory cells during muscle injury and repair is to place what has been learned in vitro into the complex and dynamic in vivo environment.
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            Mechanisms of exercise-induced muscle fibre injury.

            Exercise for which a skeletal muscle is not adequately conditioned results in focal sites of injury distributed within and among the fibres. Exercise with eccentric contractions is particularly damaging. The injury process can be hypothesised to occur in several stages. First, an initial phase serves to inaugurate the sequence. Hypotheses for the initial event can be categorised as either physical or metabolic in nature. We argue that the initial event is physical, that stresses imposed on sarcolemma by sarcomere length inhomogeneities occurring during eccentric contractions cause disruption of the normal permeability barrier provided by the cell membrane and basal lamina. This structural disturbance allows Ca++ to enter the fibre down its electrochemical gradient, precipitating the Ca++ overload phase. If the breaks in the sarcolemma are relatively minor, the entering Ca++ may be adequately handled by ATPase pumps that sequester and extrude Ca++ from the cytoplasm ('reversible' injury). However, if the Ca++ influx overwhelms the Ca++ pumps and free cytosolic Ca++ concentration rises, the injury becomes 'irreversible'. Elevations in intracellular Ca++ levels activate a number of Ca(++)-dependent proteolytic and phospholipolytic pathways that are indigenous to the muscle fibres, which respectively degrade structural and contractile proteins and membrane phospholipids; for instance, it has been demonstrated that elevation of intracellular Ca++ levels with Ca++ ionophores results in loss of creatine kinase activity from the fibres through activation of phospholipase A2 and subsequent production of leukotrienes. This autogenetic phase occurs prior to arrival of phagocytic cells, and continues during the inflammatory period when macrophages and other phagocytic cells are active at the damage site. The phagocytic phase is in evidence by 2 to 6 hours after the injury, and proceeds for several days. The regenerative phase then restores the muscle fibre to its normal condition. Repair of the muscle fibres appears to be complete; the fibres adapt during this process so that future bouts of exercise of similar type, intensity, and duration cause less injury to the muscle.
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              Biochemical mechanisms for oxygen free radical formation during exercise.

              The biochemical mechanisms behind skeletal muscle soreness and damage with muscular overuse have remained unclear. Recently, however, a growing amount of evidence indicates that free radicals play an important role as mediators of skeletal muscle damage and inflammation. During exercise, two of the potentially harmful free radical generating sources are semiquinone in the mitochondria and xanthine oxidase in the capillary endothelial cells. During high intensity exercise the flow of oxygen through the skeletal muscle cells is greatly increased at the same time as the rate of ATP utilisation exceeds the rate of ATP generation. The metabolic stress in the cells causes several biochemical changes to occur, resulting in a markedly enhanced rate of production of oxygen free radicals from semiquinone and xanthine oxidase. During normal conditions free radicals are generated at a low rate and subsequently taken care of by the well developed scavenger and antioxidant systems. However, a greatly increased rate of free radical production may exceed the capacity of the cellular defence system. Consequently, a substantial attack of free radicals on the cell membranes may lead to a loss of cell viability and to cell necrosis and could initiate the skeletal muscle damage and inflammation caused by exhaustive exercise.
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                Author and article information

                Journal
                Einstein (Sao Paulo)
                Einstein (Sao Paulo)
                eins
                Einstein
                Instituto Israelita de Ensino e Pesquisa Albert Einstein
                1679-4508
                2317-6385
                Apr-Jun 2017
                Apr-Jun 2017
                : 15
                : 2
                : 186-191
                Affiliations
                [1 ]Universidade Estadual do Oeste do Paraná, Cascavel, PR, Brazil.
                Author notes
                Corresponding author: Regina Inês Kunz − Rua Universitária, 2,069 – Zip code: 85819-110 − Cascavel, PR, Brazil − Phone: (55 45) 3220-7405 − E-mail: regina_kunz@ 123456hotmail.com

                Conflict of interest: none.

                Article
                S1679-45082017AO3967
                10.1590/S1679-45082017AO3967
                5609615
                28767917
                05c07045-4779-412c-ace6-f745632193fa

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 December 2016
                : 12 April 2017
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 29, Pages: 6
                Categories
                Original Article

                muscle, skeletal,muscle denervation,peripheral nerve injuries,rehabilitation,biological products

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