Abstract
Microcystis aeruginosa is a cyanobacterium that produces a variety of cyclic heptapeptide toxins in freshwater. The protective effects of the macromolecular container cucurbit[7]uril (CB7) were evaluated using mouse models of cyanotoxin-induced liver damage. Biochemical analysis of liver function was performed to gauge the extent of liver damage after exposure to cyanobacterial crude extract [CCE; LD50 = 35 mg/kg body weight; intraperitoneal (i.p.)] in the absence or presence of CB7 (35 mg/kg body weight, i.p.). CCE injection resulted in liver enlargement, potentiated the activities of alanine aminotransferase (ALT) and glutathione S-transferase (GST), increased lipid peroxidation (LPO), and reduced protein phosphatase 1 (PP1) activity. CCE-induced liver enlargement, ALT and GST activities, and LPO were significantly reduced when CB7 was coadministered. Moreover, the CCE-induced decline of PP1 activity was also ameliorated in the presence of CB7. Treatment with CB7 alone did not affect liver function, which exhibited a dose tolerance of 100 mg/kg body wt. Overall, our results illustrated that the addition of CB7 significantly reduced CCE-induced hepatotoxicity (P < 0.05).
Highlights
The use of synthetic macromolecules for biological and medicinal applications has always been a popular approach (Yin et al, 2021)
Co-administration of CB7 and cyanobacterial crude extract (CCE) significantly nullified the increase in liver mass that was seen in group 3 (1.88 vs. 2.77 g; P < 0.05), which implies a protective effect of CB7 on CCE-induced liver enlargement
Our results show that CCE induced liver enlargement resulting from massive intrahepatic hemorrhage, which is consistent with previous findings that MC-LR inhibits phosphatase 1 (PP1), a serine/threonine phosphatase (Honkanen et al, 1990)
Summary
The use of synthetic macromolecules for biological and medicinal applications has always been a popular approach (Yin et al, 2021). CBs are molecular containers comprising two hydrophilic carbonyl-lined portals with a central hydrophobic cavity. They have been synthesized in different sizes (Figure 1 for cucurbit[7]uril [CB7]) (Lee et al, 2003). Because of these properties, the bioactivity of the CB7 host–guest complexes (Cheng et al, 2018) and their clinical applications in vitro and in vivo have been confirmed by several studies. Another study reported that a high affinity between CB7 and sorafenib, an anticancer drug (Yang et al, 2017), and bedaquiline (Kuok et al, 2018) and clofazimine (Li et al, 2016), antituberculosis drugs, enabled the host to decrease the cardiotoxicity of these drugs without
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