Developmental toxicity, antioxidant, and marker enzyme assessment of swertiamarin in zebrafish (Danio rerio)

Abstract

A secoiridoid glycoside called swertiamarin has been widely used as a herbal medicine for many decades. In particular, swertiamarin from the Enicostema axillare herb has been used as a multipurpose drug to treat innumerable health problems. As this medicine is consumed orally, its toxicity level should be determined. To examine the safety of this compound, toxicology work was done in zebrafish, and this is the first report to describe swertiamarin toxicity in zebrafish. Zebrafish embryos were used in this swertiamarin toxicity study, and morphological changes were observed. Further, the compound was also studied in adult zebrafish to determine the impact of the compound on the fish liver.Enzyme profiling with superoxide dismutase, glutathione peroxidase, catalase, reduced glutathione levels, glutathione S-transferase, lactate dehydrogenase, glutamic oxaloacetic transaminases, lipid peroxidation, Na + /K + -ATPase, and glutamic pyruvic transaminases) was evaluated (p ≤ 0.05). Results suggest that swertiamarin is a safe drug only at a low concentration (40 µM). This study also shows that even herbal medicinal compounds may be toxic to humans at higher dosages. Hence, irrespective of whether a drug is synthetic or natural, it needs to be tested for its toxicity before use in humans.

Use of the Zebrafish Model as a tool to evaluate the anti- inflammatory and antioxidant activity of molecules. Literature Review

“…Plants are a source of nature's most important secondary metabolites, the generation of extracts and their application in treatments or to identify new specific substances used to make medicines, the potential of these extracts is of great importance for the food and pharmaceutical industry. (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) In the first phase of the metabolite revision, it was observed that in several studies plant extracts were used for both antioxidant and anti-inflammatory activity tests, five of the reviewed studies used extracts, mainly freeze-dried, Boeri et al (14) and Nguyen T. (31) performed an extraction in organic solvents that are toxic to zebrafish, so it is necessary to remove these solvents before using the compound, while Pradeep et al (32) used the fraction in ethanol, Conducting tests to determine oxidative stress directly with the extract; this indicates that the status of the metabolite's final product is a factor that can influence the antioxidant activity and in vivo analysis of the model.…”

“…Fertilized eggs were used in the early stages of development, with Mohamad Shariff et al (19) , Pradeep et al (18) and Boeri et al (14) , at 1-hour post-fertilization (h.d.f), (14,16,21) between 2 and 6 h.p.f. (20) It occupied fish of 10 h.p.f, while, in the other studies embryos of 1-and 3-days postfertilization was used (d.p.f).…”

Uso del modelo de pez cebra como herramienta para evaluar la actividad antiinflamatoria y antioxidante de los alimentos. Revisión de literatura

“…Otro de los métodos más comunes en estos estudios, fueron las cuantificaciones de actividad enzimática, (Perumal et al, 2021) realizaron varios análisis para enzimas CAT (catalasa), SOD (superóxido dismutasa), GSH (glutatión reducido), GPx (glutatión peroxidasa), GST (glutatión S-transferasa), además de peroxidación lipídica, si bien, en este grupo de metabolitos no se observó una gran presencia de estos estudios, en los otros grupos se incrementa la importancia de los mismos.…”

“…Se usó huevos fecundados en etapas tempranas de desarrollo, con (Mohamad Shariff et al, 2020), (Pradeep et al, 2019) y (Boeri et al, 2020) a 1 hora post fertilización (h.d.f), (Perumal et al, 2021), (Wang & Liu, 2020), (Boeri et al, 2020) entre 2 y 6 h.p.f, (Udaya et al, 2020) ocupó peces de 10 h.p.f, mientras que, en los otros estudios se usó embriones de 1 y 3 días post fertilización (d.p.f). Mientras que en ensayos para estrés oxidativo solo en tres estudios se emplearon oxidantes, AAPH (dihidrocloruro de 2,2'-azobis (2amidinopropano) con (Boeri et al, 2020), sulfato de cobre con (Nguyen et al, 2020)y oxazolona con (Poornima et al, 2019).…”

Developmental toxicity of the emerging contaminant cyclophosphamide and the integrated biomarker response (IBRv2) in zebrafish

“…30 Lipid peroxidation (LPO) is an antioxidant which is involved in the oxidation process of phospholipids during the antioxidant defence process. 31 Thus, antioxidants are widely used as biological health indicators of aquatic inhabitants. Likewise, the toxic effect of chemicals on tissues could be evaluated by assessing histopathology.…”