Acute Toxicity Study and Anti-Inflammatory Effect of Injectable Nanodispersion of Bixa orellana L. (Chronic In®) in Danio rerio (Zebrafish)

Abstract

Luciana Paes Gomes, Nayara Nilcia Dias Colares, Helison De Oliveira Carvalho, Bianca Vitoria Monteiro Ferreira, Vinícius Maciel Vilhena, Gabriel da Costa Furtado, Danna Emanuelle Santos Gonçalves, Aline Lopes do Nascimento, Tamiris Marques Lage, Irma Danielle Rodrigues Pedro, Heitor Ribeiro da Silva, Erdi Can Aytar and Jose Carlos Tavares Carvalho

Medicinal plants hold great potential for developing drugs to treat inflammatory diseases. Bixa orellana L, popularly known as “annatto” or “urucum”, stands out among various species. Due to its experimental at-tributes, the Zebrafish (Danio rerio) is a small tropical freshwater fish highlighted as an experimental model in pharmacological and toxicological tests of new drugs. This study aims to evaluate the acute toxicological effects and anti-inflammatory activity of the injectable nanodispersion of Bixa orellana (NBO, Chronic In®) in zebrafish. The stability of the NBO was assessed with an average particle size ranging from 53.15 ± 0.64 nm to 59.90 ± 3.63 nm. The acute toxicity study used intraperitoneal doses of NBO ranging from 250 to 1500 mg/kg. The results showed significant toxic effects at doses of 750, 1000, and 1500 mg/kg, with histopathological changes in the liver, kidneys, and intestine. The 50% lethal dose (LD50) calculation corresponded to 830.6 mg/kg. In silico tests, the detected toxicity mechanism may be related to inhibiting the cardiac potassium channel (hERG II) and/or the TNF tumor necrosis factor receptor-associated protein 1 (TRAP1). In the an-ti-inflammatory evaluation of NBO in a model of intraperitoneal edema induced by carrageenan in Zebrafish, a significant anti-inflammatory effect was observed at doses of 20 and 40 mg/kg (i.p), without sig- nificant histopathological alterations in the organs evaluated. In summary, NBO has an anti-inflammatory effect at low doses and demonstrated that doses of NBO ranging from 500 to 1500 mg/kg applied intraperitoneally were unsafe and showed toxic effects and lethality as the dose increased.

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