Doxycycline hyclate: A schistosomicidal agent in vitro with immunomodulatory potential on granulomatous inflammation in vivo

Dias, M.V.S.; Castro, Aline Pereira; Campos, Camila Cabral; Silva, Thaiany Goulart de Souza e; Gonçalves, Reggiani Vilela; Souza, Raquel Lopes Martins; Marques, Marcos José; Novaes, Rômulo Dias

doi:10.1016/j.intimp.2019.02.032

Cited by 12 publications

(19 citation statements)

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“…Microstructural changes in the integument, similar to those identified in our study, such as bubbles, erosion/flaking and body retraction, were also observed with the use of the antibiotic, doxycycline, especially at higher concentrations (Dias et al ., 2019). In the same study, the disappearance, flattening and the collapse of tubercles were also observed.…”

Section: Discussionmentioning

confidence: 99%

Antiparasitic effects of ethanolic extracts of Piper arboreum and Jatropha gossypiifolia leaves on cercariae and adult worms of Schistosoma mansoni

et al. 2020

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New treatment strategies for schistosomiasis should be evaluated, since resistant strains to the only available drug, Praziquantel, have already been described. Thus, we demonstrated antiparasitic effects of ethanolic extracts of Jatropha gossypiifolia and Piper arboreum on cercariae and adult worms of Schistosoma mansoni. The bioassays were performed at 0–10 000 μg mL−1 concentration for 0–72 h. Adult worms were stained with carmine to assess external and internal damage. The chemical screening was performed using high-performance liquid chromatography. P. arboreum displayed the best cercaricidal effect, with a 100% reduction in viability in just 60 min. The extract of J. gossypiifolia was more effective against adult worms, with 100% viability reduction of male and female worms after 12 and 24 h, respectively. P. arboreum and J. gossypiifolia were equally effective in inhibiting the oviposition of S. mansoni (93% reduction) and causing damage to internal and external structures in adult worms. Flavonoids were identified in both the extracts and phenolic compounds and amides only in P. arboreum. Thus, for the first time, it was proven that ethanolic extracts of P. arboreum and J. gossypiifolia leaves are biologically active against cercariae and adult worms of S. mansoni in vitro.

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Section: Discussionmentioning

confidence: 99%

Antiparasitic effects of ethanolic extracts of Piper arboreum and Jatropha gossypiifolia leaves on cercariae and adult worms of Schistosoma mansoni

et al. 2020

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“…The morphological integrity of the integument of adult S. mansoni worms was evaluated by scanning electron microscopy (SEM) [ 20 ]. After the toxicity test, the worms were collected and fixed for 24 h in 10% buffered formalin (pH 7.2).…”

Section: Methodsmentioning

confidence: 99%

“…The worms were dehydrated in a series of increasing concentrations of ethanol (1x at 50%, 70%, 90%, 95%, and 3x at 99.98%, 1h immersion in each concentration.) and dried in an oven at 60 ºC for 12 h. They were mounted on metallic supports, coated with gold (Modular Balzers Union FDU 010, SCA 010, Oerlikon Balzers, Balzers, Liechtenstein), and examined with a scanning electron microscope (Leo 1430VP; Carl Zeiss, Jena, Thuringia, Germany) [ 20 ]. The integumentary integrity was analyzed in worms treated FB1, FB4 and FB9 at four different concentrations, two below (FB1, 0.104 and 0.208 mM; FB4, 0.080 and 0.161 mM; FB9, 0.203 and 0.270 mM) and two above (FB1, 0.416 and 0.521 mM; FB4, 0.242 and 0.322 mM; FB9, 0.405 and 0.473 mM) the ED 50 .…”

Section: Methodsmentioning

confidence: 99%

In vitro and in silico evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools

Souza

Novaes

Gonçalves

et al. 2022

J. Venom. Anim. Toxins incl. Trop. Dis

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Background: Eugenol shows both antibacterial and antiparasitic activities, suggesting that it might be evaluated as an option for the treatment of praziquantel-resistant schistosome. Methods: The in vitro activities of three eugenol derivatives (FB1, FB4 and FB9) on adult worms from Schistosoma mansoni were examined by fluorescence and scanning electron microscopy to analyze effects on the excretory system and integument damage, respectively. Biochemical tests with verapamil (a calcium channel antagonist) and ouabain (a Na + /K + -ATPase pump inhibitor) were used to characterize eugenol derivative interactions with calcium channels and the Na + /K + -ATPase, while in silico analysis identified potential Na + /K + -ATPase binding sites. Results: The compounds showed effective doses (ED 50 ) of 0.324 mM (FB1), 0.167 mM (FB4), and 0.340 mM (FB9). In addition, FB4 (0.322 mM), which showed the lowest ED 50, ED 90 and ED 100 (p < 0.05), caused the most damage to the excretory system and integument, according to both fluorescence and scanning electron microscopy analysis. The death of adult worms was delayed by ouabain treatment plus FB1 (192 versus 72 hours) and FB9 (192 versus 168 hours), but the response to FB4 was the same in the presence or absence of ouabain. Besides, no changes were noted when all of the eugenol derivatives were combined with verapamil. Moreover, FB1 and FB9 inhibited

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“…The enzymatic activity of matrix metalloproteases in macrophage homogenate was measured using a fluorometric enzymatic kit, according to the manufacturer's instructions (ABCAM, Cambridge, MA, USA). The MMP activity was measured at 490 nm/525 nm (excitation/emission), as previously reported [28].…”

Section: 12mentioning

confidence: 99%

Doxycycline Hyclate Modulates Antioxidant Defenses, Matrix Metalloproteinases, and COX-2 Activity Accelerating Skin Wound Healing by Secondary Intention in Rats

Altoé

Alves

Miranda

et al. 2021

Oxidative Medicine and Cellular Longevity

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The main objective of this study was to investigate the action of doxycycline hyclate (Dx) in the skin wound healing process in Wistar rats. We investigated the effect of Dx on inflammatory cell recruitment and production of inflammatory mediators via in vitro and in vivo analysis. In addition, we analyzed neovascularization, extracellular matrix deposition, and antioxidant potential of Dx on cutaneous repair in Wistar rats. Male animals ( n = 15 ) were divided into three groups with five animals each (protocol: 72/2017), and three skin wounds (12 mm diameter) were created on the back of the animals. The groups were as follows: C, received distilled water (control); Dx1, doxycycline hyclate (10 mg/kg/day); and Dx2, doxycycline hyclate (30 mg/kg/day). The applications were carried out daily for up to 21 days, and tissues from different wounds were removed every 7 days. Our in vitro analysis demonstrated that Dx led to macrophage proliferation and increased N-acetyl-β-D-glucosaminidase (NAG) production, besides decreased cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and metalloproteinases (MMP), which indicates that macrophage activation and COX-2 inhibition are possibly regulated by independent mechanisms. In vivo, our findings presented increased cellularity, blood vessels, and the number of mast cells. However, downregulation was observed in the COX-2 and PGE2 expression, which was limited to epidermal cells. Our results also showed that the downregulation of this pathway benefits the oxidative balance by reducing protein carbonyls, malondialdehyde, nitric oxide, and hydrogen peroxide (H2O2). In addition, there was an increase in the antioxidant enzymes (catalase and superoxide dismutase) after Dx exposure, which demonstrates its antioxidant potential. Finally, Dx increased the number of types I collagen and elastic fibers and reduced the levels of MMP, thus accelerating the closure of skin wounds. Our findings indicated that both doses of Dx can modulate the skin repair process, but the best effects were observed after exposure to the highest dose.

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Doxycycline hyclate: A schistosomicidal agent in vitro with immunomodulatory potential on granulomatous inflammation in vivo

Cited by 12 publications

References 70 publications

Antiparasitic effects of ethanolic extracts of Piper arboreum and Jatropha gossypiifolia leaves on cercariae and adult worms of Schistosoma mansoni

Antiparasitic effects of ethanolic extracts of Piper arboreum and Jatropha gossypiifolia leaves on cercariae and adult worms of Schistosoma mansoni

In vitro and in silico evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools

Doxycycline Hyclate Modulates Antioxidant Defenses, Matrix Metalloproteinases, and COX-2 Activity Accelerating Skin Wound Healing by Secondary Intention in Rats

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