<p><i>Cryptococcus neoformans</i> var. <i>grubii</i>, an encapsulated yeast ubiquitously found in the environment, is an opportunistic mycosis that causes molecular, cellular, and tissue damage in immunocompromised patients due to the production of many enzymes that have digestive potential to degrade host molecules, causing hematological, hepatic, and renal damage. Natural plant-based products, like rutin, are emerging as protective agents against hematological, hepatic, and renal damage. In this sense, we can emphasize the flavonoid rutin, a potent antifungal molecule against fungi belonging to the genus <i>Cryptococcus</i>. However, the protective effects of rutin on <i>C. neoformans</i> var. <i>grubii</i>-elicited hematological, hepatic, and renal damages remain unknown. Thus, the study aimed to investigate the protective effects of rutin on hematological, biochemical, and pathological parameters of rats experimentally infected by <i>C. neoformans</i> var. <i>grubii.</i> Erythrocyte count, hemoglobin content, and hematocrit levels were significantly reduced in rats treated with saline solution and infected by <i>C. neoformans</i> var. <i>grubii</i>, compared to rats treated with saline solution and uninfected, while total leukocytes and their subtypes significantly increased. Biomarkers of hepatic (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels) and renal (urea levels) functions were significantly increased in rats treated with saline solution and infected by <i>C. neoformans</i> var. <i>grubii</i>, compared to rats treated with saline solution and uninfected, while albumin reduced significantly in rats treated with saline solution and infected by <i>C. neoformans</i> var. <i>grubii</i>, compared to rats treated with saline solution and uninfected. Rutin treatment prevented the impairment of hematological parameters of red blood cells caused by the disease but did not exert protective effects on hematological parameters linked to white blood cells (total leukocytes and neutrophils, lymphocytes, monocytes, and eosinophils). This treatment ameliorated the increase in aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase activities caused by the disease. Rutin (50&#xa0;mg/kg) effectively mitigated anemia and liver injury caused by <i>C. neoformans</i> var. <i>grubii</i> in rats, likely due to its antioxidant and cytoprotective properties. However, its inability to reverse leukocytosis and renal impairment suggests that further optimization of dose and duration, or combination therapy, may enhance its efficacy. These findings support the potential of rutin as a supportive therapy in fungal infections with hepatic and hematological involvement.</p>

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Rutin mitigates hematological and hepatic damage in rats infected with Cryptococcus neoformans

  • Mariana Tonelotto Lorenzoni,
  • Helena Ritter Rebelato,
  • Alice Rodrigues Mazaro,
  • Rúbia Schallenberger da Silva,
  • Cinthia Melazzo de Andrade,
  • Teodoro Trevisan De Paula Martins,
  • Isabela Maraschin Vieira,
  • Maria Eduarda de Ávila Biscaglia Vieira,
  • Marcelo Leite da Veiga,
  • Carolina Rapachi Fortes,
  • Aline Rossato,
  • Larissa Da Silva Silveira,
  • Liana Da Silva Fernandes,
  • Michele Rorato Sagrillo,
  • Raquel Tusi Tamiosso,
  • Matheus Dellaméa Baldissera

摘要

Cryptococcus neoformans var. grubii, an encapsulated yeast ubiquitously found in the environment, is an opportunistic mycosis that causes molecular, cellular, and tissue damage in immunocompromised patients due to the production of many enzymes that have digestive potential to degrade host molecules, causing hematological, hepatic, and renal damage. Natural plant-based products, like rutin, are emerging as protective agents against hematological, hepatic, and renal damage. In this sense, we can emphasize the flavonoid rutin, a potent antifungal molecule against fungi belonging to the genus Cryptococcus. However, the protective effects of rutin on C. neoformans var. grubii-elicited hematological, hepatic, and renal damages remain unknown. Thus, the study aimed to investigate the protective effects of rutin on hematological, biochemical, and pathological parameters of rats experimentally infected by C. neoformans var. grubii. Erythrocyte count, hemoglobin content, and hematocrit levels were significantly reduced in rats treated with saline solution and infected by C. neoformans var. grubii, compared to rats treated with saline solution and uninfected, while total leukocytes and their subtypes significantly increased. Biomarkers of hepatic (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels) and renal (urea levels) functions were significantly increased in rats treated with saline solution and infected by C. neoformans var. grubii, compared to rats treated with saline solution and uninfected, while albumin reduced significantly in rats treated with saline solution and infected by C. neoformans var. grubii, compared to rats treated with saline solution and uninfected. Rutin treatment prevented the impairment of hematological parameters of red blood cells caused by the disease but did not exert protective effects on hematological parameters linked to white blood cells (total leukocytes and neutrophils, lymphocytes, monocytes, and eosinophils). This treatment ameliorated the increase in aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase activities caused by the disease. Rutin (50 mg/kg) effectively mitigated anemia and liver injury caused by C. neoformans var. grubii in rats, likely due to its antioxidant and cytoprotective properties. However, its inability to reverse leukocytosis and renal impairment suggests that further optimization of dose and duration, or combination therapy, may enhance its efficacy. These findings support the potential of rutin as a supportive therapy in fungal infections with hepatic and hematological involvement.