Search

Secretions of beneficial intestinal bacteria can inhibit the growth and biofilm formation of a wide range of microorganisms. Curcumin has shown broad spectrum antioxidant, anti-inflammatory, and antimicrobial potential. It is important to evaluate the influence of these secretions with bioactive peptides, in combination with curcumin, to limit growth and inhibit biofilm formation of pathogenic bacteria of importance in aquaculture. In the present study, the supernatants of Lactoccocus lactis NZ9000, Lactobacillus rhamnosus GG and Pediococcus pentosaceus NCDO 990, and curcumin (0,1,10,25 and 50 μM) were used to evaluate their efficacy in growth, inhibition biofilm and membrane permeability of Aeromonas hydrophila CAIM 347 (A. hydrophila). The supernatants of probiotics and curcumin 1,10 and 25 μM exerted similar effects in reducing the growth of A. hydrophila at 12 h of interaction. The supernatants of the probiotics and curcumin 25 and 50 μM exerted similar effects in reducing the biofilm of A. hydrophila. There is a significant increase in the membrane permeability of A. hydrophila in interaction with 50 μM curcumin at two hours of incubation and with the supernatants separately in the same period. Different modes of action of curcumin and bacteriocins separately were demonstrated as effective substitutes for antibiotics in containing A. hydrophila and avoiding the application of antibiotics. The techniques implemented in this study provide evidence that there is no synergy between treatments at the selected concentrations and times., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Doxazosin and carvedilol have been evaluated as an alternative treatment against chronic liver lesions and for their possible role during the regeneration of damage caused by liver fibrosis in a hamster model. However, these drugs have been reported to induce morphological changes in hepatocytes, affecting the recovery of liver parenchyma. The effects of these α /𝛽 adrenoblockers on the viability of hepatocytes are unknown. Herein, we demonstrate the protective effect of curcumin against the possible side effects of doxazosin and carvedilol, drugs with proven antifibrotic activity. After pretreatment with 1  μ M curcumin for 1 h, HepG2 cells were exposed to 0.1-25  μ M doxazosin or carvedilol for 24, 48, and 72 h. Cell viability was assessed using the MTT assay and SYTOX green staining. Morphological changes were detected using the hematoxylin and eosin (H&E) staining and scanning electron microscopy (SEM). An expression of apoptotic and oxidative stress markers was analyzed using reverse transcription-quantitative PCR (RT-qPCR). The results indicate that doxazosin decreases cell viability in a time- and dose-dependent manner, whereas carvedilol increases cell proliferation; however, curcumin increases or maintains cell viability. SEM and H&E staining provided evidence that doxazosin and carvedilol induced morphological changes in HepG2 cells, and curcumin protected against these effects, maintaining the morphology in 90% of treated cells. Furthermore, curcumin positively regulated the expression of Nrf2 , HO-1 , and SOD1 mRNAs in cells treated with 0.1 and 0.5  μ M doxazosin. Moreover, the Bcl-2 / Bax ratio was higher in cells that were treated with curcumin before doxazosin or carvedilol. The present study demonstrates that curcumin controls doxazosin- and carvedilol-induced cytotoxicity and morphological changes in HepG2 cells possibly by overexpression of Nrf2 ., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Mariana Yazmin Medina-Pizaño et al.)

Liver cirrhosis is the result of an uncontrolled fibrogenetic process, due to the activation and subsequent differentiation into myofibroblasts of the hepatic stellate cells (HSC). It is known that HSC express adrenoreceptors (AR), and the use of AR antagonists protects experimental animals from cirrhosis. However, several studies suggest that the toxicity generated by metabolism of these antagonists would hinder its use in cirrhotic patients. In addition, liver fibrosis may be associated with a decrease of the antioxidant response of the nuclear factor erythroid 2-related factor 2 (Nrf-2) and the overregulation of the proinflammatory pathway of nuclear factor kappa B (NF- κ B). Therefore, in the present work, the capacity of doxazosin ( α 1 antagonist), carvedilol (nonselective beta-adrenoceptor blocker with alpha 1-blocking properties), and curcumin (antioxidant and anti-inflammatory compound) to reverse liver cirrhosis and studying the possible modulation of Nrf-2 and NF- κ B were evaluated. Hamsters received CCl4 for 20 weeks, and then treatments were immediately administered for 4 weeks more. The individual administration of doxazosin or carvedilol showed less ability to reverse cirrhosis in relation to concomitantly curcumin administration. However, the best effect was the combined effect of doxazosin, carvedilol, and curcumin, reversing liver fibrosis and decreasing the amount of collagen I (Sirius red stain) without affecting the morphology of hepatocytes (hematoxylin and eosin stain), showing normal hepatic function (glucose, albumin, AST, ALT, total bilirubin, and total proteins). In addition, carvedilol treatment and the combination of doxazosin with curcumin increased Nrf-2/NF- κ B mRNA ratio and its protein expression in the inflammatory cells in the livers, possibly as another mechanism of hepatoprotection. Therefore, these results suggest for the first time that α / β adrenergic blockers with curcumin completely reverse hepatic damage, possibly as a result of adrenergic antagonism on HSC and conceivably by the increase of Nrf-2/NF- κ B mRNA ratio.

Amoebic liver abscess (ALA) is the most common extraintestinal amoebiasis caused by Entamoeba histolytica ( E. histolytica ). However, despite current knowledge and scientific advances about this infection, there are no effective treatments to prevent it. Herein, the antiamoebic capacity of curcumin in a hamster model was evaluated. Curcumin (150 mg/kg, p.o., daily during 10 days before infection) considerably prevents liver damage induced at 12 and 48 h post-intrahepatic inoculation of trophozoites and decreases ALT, ALP, and γ -GTP activities, and macroscopic and microscopic observations were consistent with these results. On the other hand, after one week of intraportal inoculation, liver damage was prevented by curcumin (150 mg/kg, p.o., daily, 20 days before amoebic inoculation and during the week of infection); liver/body weight ratios and tissue and histological stains showed normal appearance; in addition, the increases in ALT, ALP, and γ -GTP activities were prevented; the depletion of glycogen content induced by the amoebic damage was partially but significantly prevented, while NF- κ B activity was inhibited and the expression of IL-1 β was reduced; Nrf2 production showed a tendency to increase it, and HO-1 protein was overexpressed. These results suggest for the first time that curcumin can be a compound with antiamoebic effect in the liver, suggesting that its daily use could help greatly decrease the incidence of this type of infection.