Effect of modified citrus pectin on galectin-3 inhibition in cisplatin-induced cardiac and renal toxicity.

This study evaluated the effect of pharmacological inhibition of galectin 3 (Gal-3) with modified citrus pectin (MCP) on the heart and kidney in a model of cisplatin-induced acute toxicity. Male Wistar rats were divided into four groups (n = 6/group): SHAM, which received sterile saline intraperitoneally (i.p.) for three days; CIS, which received cisplatin i.p. (10 mg/kg/day) for three days; MCP, which received MCP orally (100 mg/kg/day) for seven days, followed by sterile saline i.p. for three days; MCP+CIS, which received MCP orally for seven days followed by cisplatin i.p. for three days. The blood, heart, and kidneys were collected six hours after the last treatment. MCP treatment did not change Gal-3 protein levels in the blood and heart, but it did reduce them in the kidneys of the MCP groups compared to the SHAM group. While no morphological changes were evident in the cardiac tissue, increased malondialdehyde (MDA) levels and deregulation of the mitochondrial oxidative phosphorylation system were observed in the heart homogenates of the MCP+CIS group. Cisplatin administration caused acute tubular degeneration in the kidneys; the MCP+CIS group also showed increased MDA levels. In conclusion, MCP therapy in the acute model of cisplatin-induced toxicity increases oxidative stress in cardiac and renal tissues. Further investigations are needed to determine the beneficial and harmful roles of Gal-3 in the cardiorenal system since it can act differently in acute and chronic diseases/conditions.

Lack of Annexin A1 Exacerbates Inflammatory Response in Acute Endometritis Model.

Annexin A1 (AnxA1) is a glucocorticoid-inducible protein and an important endogenous modulator of inflammation. However, its effect in the endometrial microenvironment is poorly explained. This study aimed to evaluate the role of endogenous AnxA1 in an endometritis mouse model induced by lipopolysaccharide (LPS). Female C57BL/6 wild-type (WT) and AnxA1-/- mice were divided into two groups: SHAM and LPS. To induce endometritis, mice received a vaginal infusion of 50 µL of LPS (1 mg/mL) dissolved in phosphate-buffered saline. After 24 h, the mice were euthanized, and blood and uteri samples were collected. The endometrium inflammatory scores were significantly increased in the LPS-treated group. AnxA1-/- mice from the LPS group demonstrated a significant increase in the number of degranulated mast cell levels compared to AnxA1-/- SHAM mice. The Western blotting analysis revealed that a lack of AnxA1 promoted the upregulation of NLRP3 and pro-IL-1ß in the acute endometritis animal model compared to WT LPS animals. LPS-induced endometritis increased the number of blood peripheral leukocytes in both WT and AnxA1-/- mice compared with SHAM group mice (p < 0.001). AnxA1-/- mice also showed increased plasma levels of IL-1ß (p < 0.01), IL-6, IL-10, IL-17, and TNF-α (p < 0.05) following LPS-induced endometritis. In conclusion, a lack of endogenous AnxA1 exacerbated the inflammatory response in an endometritis model via NLRP3 dysregulation, increased uterine mast cell activation, and plasma pro-inflammatory cytokine release.

Proteína antiinflamatória anexina 1: mecanismos celulares e relevância clínica / Anti-inflammatory protein annexin 1: cellular mechanisms and clinical relevance

Um dos eventos de importância no processo inflamatório é o recrutamento dos leucócitos da circulação sanguínea para os sítios da inflamação por meio de interações com as células endoteliais das vênulas pós-capilares. O mecanismo de recrutamento é desencadeado por uma série de mediadores pró-inflamatórios quesão produzidos por células como mastócitos, macrófagos, células endoteliais ativadas, bem como leucócitos transmigrados para o tecido inflamado. Por outro lado, a resposta inflamatória é controlada pela ação de mediadores antiinflamatórios que atuam para manter a homeostasia da resposta imunológica e prevenir alesão tecidual. Entre esses mediadores destaca-se a anexina 1, primeiro membro descrito de uma família de proteínas ligantes de fosfolipídios dependentes de cálcio, com seqüências de aminoácidos altamente conservadas nos vertebrados. Esta proteína atua como um potente modulador endógeno da inflamação,inibindo a atividade de enzimas que atuam na produção de mediadores pró-inflamatórios e interferindo no processo de transmigração dos leucócitos. Nesta revisão, a estrutura, a expressão, os mecanismos de açãoe os efeitos farmacológicos da anexina 1 em diferentes modelos experimentais são abordados. O objetivo final das investigações é avaliar a adequação do uso da anexina 1 como um agente terapêutico eficaz no tratamento de patologias causadas pela inflamação, como a artrite reumatóide, lesão do miocárdio por isquemia-reperfusão, neoplasias e asma, por exemplo.