Dados do Trabalho

Título

The schistosomicidal activity of 5-hydroxy-2-methyl-1,4-naphthoquinone (Plumbagin) and its effect on histopathological and histomorphometric modulation of hepatic granuloma

Introdução

Schistosoma mansoni infection is potentially fatal due to hepatic granulomatous inflammation and, in the absence of a vaccine, Praziquantel (PZQ) is currently the only control and treatment strategy for millions of infected people.

Objetivo (s)

To evaluate the schistosomicidal activity of plumbagin (PLUM) and its effect on granuloma in murine schistosomiasis.

Material e Métodos

Mice (n=50) were infected with 50 cercariae of S. mansoni and equally distributed into 5 groups: negative control group (G1), positive control group treated with PZQ (50mg/kg/day) (G2), and groups treated with 8 (G3), 16 (G4), or 32 (G5) mg/kg/day of PLUM. Treatment was performed by gavage from the 45th to the 49th day of infection. Kato-Katz was performed at the beginning of the treatment and on the 60th day, the day of euthanasia. The animals were perfused to evaluate the parasitic load (total and female worms), and their organs recovered to evaluate the load of eggs in the hepatic and intestinal tissues, the oviposition pattern, and histopathological and histomorphometric analysis of hepatic tissue and granulomas.

Resultados e Conclusão

PLUM reduced the number of eggs eliminated in the feces by 65, 71, and 82%, as well as reduced (p < 0.001) the total worm burden by 46.7, 55.2, and 72.4%, and the female worm burden at 44, 53, and 71.16% in mice treated with 8, 16, and 32 mg/kg, respectively. In evaluating the intestinal tissue, PLUM altered the oviposition by reducing the percentage of immature eggs (-65%) and increased about 10 times the percentage of dead eggs. In the PZQ group, we did not visualize eggs in the feces, the reduction in the worm load was 100%, in addition to causing an ovicidal effect with about 90% of the eggs dead in the intestinal tissue. PLUM reduced the egg load in liver tissue by 36, 46, and, 64%, and in intestinal tissue by 57, 65, and 80% for doses of 8, 16, and 32 mg\kg, respectively. PLUM reduced the numerical density by 41, 48, and 71% and the volume of hepatic granulomas by 49.56, 57.63, and 71.21%, respectively. Furthermore, PLUM caused histopathological improvement of granulomas in a dose-dependent manner by reducing the inflammatory infiltrate with a reduction in polymorphonuclear cells. PLUM is a promising schistosomicidal candidate, acting not only on parasitological parameters but also on hepatic granuloma.

Palavras-chave

Schistosomicidal, Histopathology, Naphthoquinones, Schistosoma mansoni, plumbagin.

Agradecimentos

CAPES - Code 001, FACEPE (APQ-0498-4.03/19, APQ-1181-4.03/22)