The numerous side effects of platinum based chemotherapy has led to the design of new therapeutics with platinum replaced by another transition metal. Here, we investigated the interactions of previously reported copper(II) complexes containing S-isoalkyl derivatives, the salicylic acid with guanosine-5′-monophosphate and calf thymus DNA (CT-DNA) and their antitumor effects, in a colon carcinoma model. All three copper(II) complexes exhibited an affinity for binding to CT-DNA, but there was no indication of intercalation or the displacement of ethidium bromide. Molecular docking studies revealed a significant affinity of the complexes for binding to the minor groove of B-form DNA, which coincided with DNA elongation, and a higher affinity for binding to Z-form DNA, supporting the hypothesis that the complex binding to CT-DNA induces a local transition from B-form to Z-form DNA. These complexes show a moderate, but selective cytotoxic effect toward colon cancer cells in vitro. Binuclear complex of copper(II) with S-isoamyl derivative of thiosalicylic acid showed the highest cytotoxic effect, arrested tumor cells in the G2/M phase of the cell cycle, and significantly reduced the expression of inflammatory molecules pro-IL-1β, TNF-α, ICAM-1, and VCAM-1 in the tissue of primary heterotopic murine colon cancer, which was accompanied by a significantly reduced tumor growth and metastases in the lung and liver.

Intravascular hemolysis is a central feature of congenital and acquired hemolytic anemias, complement disorders, infectious diseases, and toxemias. Massive and/or chronic hemolysis is followed by the induction of inflammation, very often with severe damage of organs, which enhances the morbidity and mortality of hemolytic diseases. Galectin-3 (Gal-3) is a β-galactoside-binding lectin that modulates the functions of many immune cells, thus affecting inflammatory processes. Gal-3 is also one of the main regulators of fibrosis. The role of Gal-3 in the development of different kidney and liver diseases and the potential of therapeutic Gal-3 inhibition have been demonstrated. Therefore, the objective of this review is to discuss the possible effects of Gal-3 on the process of kidney and liver damage induced by intravascular hemolysis, as well as to shed light on the potential therapeutic targeting of Gal-3 in intravascular hemolysis.

Background/Objectives: Acute intravascular hemolysis is associated with the release of labile heme, which contributes to systemic inflammation and organ dysfunction. Galectin-3 (Gal-3) is a known modulator of inflammatory responses. However, its specific role in heme-induced organ injury remains to be fully elucidated. Methods: We used a phenylhydrazine (PHZ)-induced model of acute hemolysis in wild-type (WT) and Gal-3 knockout (KO) mice to investigate the influence of Gal-3 on tissue alterations and the inflammatory response. Results: Despite equivalent levels of hemolysis and anemia in both genotypes, Gal-3 deficiency was associated with reduced injury in the liver, kidneys, and pancreas. In WT mice, Gal-3 was associated with a pro-inflammatory splenic microenvironment. Conversely, Gal-3 KO mice exhibited a shift toward an immunoregulatory phenotype, characterized by an increased frequency of CD4 + CD25 + FoxP3+ regulatory T cells and IL-10+ macrophages. This shift correlated with preserved organ architecture and a more controlled inflammatory profile. Conclusions: Our findings suggest that Gal-3 may act as a mediator of heme-induced systemic inflammation. By influencing the splenic immune microenvironment and promoting a regulatory phenotype, the absence of Gal-3 appears to alleviate multi-organ stress, suggesting its potential as a target for modulating complications during acute hemolytic crises.

Background/Objectives: Immune-mediated hepatitis, including autoimmune hepatitis, remains a formidable clinical challenge characterized by the rapid destruction of the liver parenchyma. While whey proteins are well-regarded for their anti-inflammatory properties, goat whey possesses a distinct bioactive profile, offering superior digestibility and reduced allergenicity compared to their bovine counterparts. This study investigated the hepatoprotective potential and underlying immunological mechanisms of lyophilized goat whey (LGW) in a Concanavalin A (ConA)-induced model of acute hepatitis. Methods: BALB/c and C57BL/6 mice were administered LGW orally (1 g/kg/day) for five consecutive days prior to a ConA challenge. Liver injury was quantified via serum transaminase levels and histopathological evaluation. The cytokine profiles and the phenotype of liver mononuclear cells (MNCs) were analyzed using ELISA and flow cytometry, respectively. Results: LGW pretreatment significantly attenuated ConA-induced hepatitis in both mouse strains, markedly reducing serum transaminase levels and preserving hepatic architecture. Mechanistically, LGW triggered a fundamental shift in the hepatic immune microenvironment by suppressing the pro-inflammatory Th1/Th17 axis (evidenced by decreased IFN-γ and IL-17) while concurrently upregulating the anti-inflammatory cytokine IL-10. Furthermore, LGW induced a tolerogenic phenotype in hepatic dendritic cells (CD11c⁺CD206⁺), which directly correlated with a significant expansion of regulatory T cells (Tregs). This strain-independent protection suggests that LGW modulates fundamental, early-stage immune signaling pathways within the liver. Conclusions: Our findings demonstrate that LGW exerts potent hepatoprotection by effectively reprogramming the hepatic immune microenvironment toward a tolerogenic state. These results position LGW as a promising, safe, and effective functional food candidate for the prevention and adjunct management of immune-mediated inflammatory liver diseases.