Protein from Hevea brasiliensis “Hev b 13” latex attenuates systemic inflammatory response and lung lesions in rats with sepsis

Araújo, Lilhian Alves de; Reis, Paulo Roberto de Melo; Mrué, Fátima; Gomes, Clayson Moura; Oliveira, Milton Adriano Pelli de; Silva, H M; Alves, Maxley Martins; Silva-Júnior, Nelson Jorge da

doi:10.1590/1519-6984.06316

Cited by 6 publications

(6 citation statements)

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“…46 Although the PPNL mechanism of action is still poorly understood, it is speculated that an interaction with immune cells might be at play, 57 as demonstrated in studies that found an anti-inflammatory response with an increase in IL-10 and a decrease in IL-1b expression after PPNL use. 3,4 Moreover, cardiac fibroblast studies suggested that IL-1b upregulation increases MMP-2 expression and that this activity may be regulated by the PKC-u, PKC-z, and NF-kB pathways. 64 Hence, when MMP-2 expression was reduced with IL-1b, an increase in collagen synthesis was found.…”

Section: Discussionmentioning

confidence: 99%

“…20 There is no consensus in the literature on the optimal treatment for Achilles tendon ruptures, but they can be treated either nonoperatively or operatively with open or percutaneous repairs; however, some studies indicate surgery as the best option, mainly for athletes. 14,35 The American Journal of Sports Medicine 2019;47 (4):901-914 DOI: 10.1177/0363546518822836 Ó 2019 The Author(s)…”

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Application of a Purified Protein From Natural Latex and the Influence of Suture Type on Achilles Tendon Repair in Rats

et al. 2019

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Background: The prolonged tendon-healing process, the high costs associated with treatment, the increase in the number of injuries over the past decades, and the lack of consensus on the optimal treatment of tendon injuries are a global problem. Restoring the normal tendon anatomy and decreasing the healing time are key factors for treatment advancement. Hypothesis: Application of a purified protein from natural latex (PPNL) accelerates the healing process, increasing collagen synthesis and decreasing metalloproteinases. PPNL associated with a simpler suture technique should decrease the healing time. Study Design: Controlled laboratory study. Methods: Injury, surgery, and treatment with PPNL were conducted with male Sprague-Dawley rats. Two suture techniques were used: U-suture, a simpler and lesser traumatic technique, and Kessler-Tajima, to avoid strangulation of the microcirculation. Achilles tendons were completely sectioned, and 100 µL of 0.1% PPNL was applied on the tendon during surgery. Tendon morphology, distribution, and quantity of collagen types I and III, as well as expression of TIMP-1, TIMP-2, MMP-2, and MMP-9 and ultrastructural aspects of cells and collagen fibrils, were assessed after 2 and 4 weeks. Results: PPNL treatment improved collagen type I synthesis and reduced MMP-2 expression. All groups showed a 6.8-times increase in tendon weight as compared with the control group after 2 weeks and a 5.2-times increase after 4 weeks. All groups showed an increase in diameter after 4 weeks, except for the ones treated with PPNL, which showed a slight reduction in diameter. The peak of concentration of collagen fibrils with a 80-nm diameter was 27.79% in the control group; all other experimental groups presented fibrils between 50 and 60 nm. However, the best results were observed with Kessler-Tajima suture associated with PPNL. Conclusion/Clinical Relevance: There are no known medicines or substances capable of aiding the tendon healing process besides surgery. The discovery of a substance able to improve this process and decrease its duration represents an important advancement in orthopaedic medicine.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Application of a Purified Protein From Natural Latex and the Influence of Suture Type on Achilles Tendon Repair in Rats

et al. 2019

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“…Previous studies associate the effect of the F1 protein with immune cells, which can regulate the expression of inflammatory cytokines [68–70]. F1 administration was able to reduce levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and increase levels of interleukin-10 (IL-10) and interleukin-4 (IL-4) which in general contribute to an anti-inflammatory effect [68–70]. Our results suggest that F1 protein may be associated with the regulation of growth factors, such as NGF and VEGF.…”

Section: Discussionmentioning

confidence: 99%

Growth factors expression and ultrastructural morphology after application of low-level laser and natural latex protein on a sciatic nerve crush-type injury

et al. 2019

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The effects of low-level laser therapy (LLLT) and natural latex protein (F1, Hevea brasiliensis) were evaluated on crush-type injuries (15kg) to the sciatic nerve in the expressions of nerve growth factor (NGF) and vascular endothelium growth factor (VEGF) and ultrastructural morphology to associate with previous morphometric data using the same protocol of injury and treatment. Thirty-six male rats were allocated into six experimental groups (n = 6): 1-Control; 2-Exposed nerve; 3-Injured nerve; 4-LLLT (15J/cm2, 780nm, 30mW, Continuous Wave) treated injured nerve; 5-F1 (0,1mg) treated injured nerve; and 6-LLLT&F1 treated injured nerve. Four or eight weeks after, sciatic nerve samples were processed for analysis. NGF expression were higher (p<0.05) four weeks after in all injured groups in comparison to Control (Med:0.8; Q1:0; Q3:55.5%area). Among them, the Injured (Med:70.7; Q1:64.4; Q3:77.5%area) showed the highest expression, and F1 (Med:17.3; Q1:14.1; Q3:21.7%area) had the lowest. At week 8, NGF expressions decreased in the injured groups. VEGF was expressed in all groups; its higher expression was observed in the injured groups 4 weeks after (Injured. Med:29.5; F1. Med:17.7 and LLLT&F1. Med:19.4%area). At week 8, a general reduction of VEGF expression was noted, remaining higher in F1 (Med:35.1; Q1.30.6; Q3.39.6%area) and LLLT&F1 (Med:18.5; Q1:16; Q3:25%area). Ultrastructural morphology revealed improvements in the treated groups; 4 weeks after, the F1 group presented greater quantity and diameter of the nerve fibers uniformly distributed. Eight weeks after, the F1 and LLLT&F1 showed similar characteristics to the non-injured groups. In summary, these results and our previous studies indicated that F1 and LLLT may favorably influence the healing of nerve crush injury. Four weeks after nerve injury F1 group showed the best results suggesting recovery acceleration; at 8th week F1 and LLLT&F1 groups presented better features and higher vascularization that could be associated with VEGF maintenance.

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“…The slides (n=8) were examined by an experienced pathologist blinded to the treatments, using a light microscope (Olympus Corp., Tokyo, Japan) at 200× magnification (100 fields per section). Lung tissue lesions were classified as described in a previous study [13].…”

Section: Methodsmentioning

confidence: 99%

The Protective Effects of Protease Inhibitor MG-132 on Sepsis-Induced Acute Lung Rats and Its Possible Mechanisms

Miao

et al. 2019

Med Sci Monit

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Background The aim of the present study was to investigate the protective effects of protease inhibitor MG-132 on sepsis-induced acute lung injury rats. Material/Methods Sprague Dawley rats were employed to induce sepsis by cecal ligation and puncture (CLP) method. Rats were divided into 4 groups: control, sham, model (CLP), and MG-132. Histopathology observation was detected by hematoxylin and eosin staining. The ratio of wet lung to dry lung (W/D) was calculated. In addition, the levels of inflammatory factors in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Also, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were evaluated. Western blotting was performed to measure the expression of hypoxia-inducible factor-1 α (HIF-1α). In order to assess the role of HIF-1α, YC-1, the inhibitor of HIF-1α, was used to treat the rats. The expression of phosphor-mTOR (p-mTOR), p-4EBP1, and p-EIF4E were evaluated by western blotting. Results Obvious pathological injury and increasing ratio of W/D in the model group were observed. Both pathological injury and W/D were improved in the MG-132 group, and the greatest improvement could be seen in the YC-1+MG-132 group. Furthermore, the MDA levels in the MG-132 group was decreased, accompanied by an increase in SOD levels. The level of HIF-1α was increased in the model group while a decreased was detected in the MG-132 group. The levels of inflammatory factors were high in the model group, whereas the opposite result was found in the MG-132 group, and the lowest in were in the YC-1+MG-132 group. Furthermore, the expression levels of p-mTOR, p-4EBP1, and p-EIF4E proteins were downregulated in the MG-132 group compared to the model group, and the lowest was in the YC-1+MG-132 group. Conclusions Our study suggested that MG-132 was able to protect against acute lung injury via inhibition of HIF-1α mediated mTOR/4EBP1/EIF4E pathway.

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Protein from Hevea brasiliensis “Hev b 13” latex attenuates systemic inflammatory response and lung lesions in rats with sepsis

Cited by 6 publications

References 32 publications

Application of a Purified Protein From Natural Latex and the Influence of Suture Type on Achilles Tendon Repair in Rats

Application of a Purified Protein From Natural Latex and the Influence of Suture Type on Achilles Tendon Repair in Rats

Growth factors expression and ultrastructural morphology after application of low-level laser and natural latex protein on a sciatic nerve crush-type injury

The Protective Effects of Protease Inhibitor MG-132 on Sepsis-Induced Acute Lung Rats and Its Possible Mechanisms

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