Curcumin Protects HepG2 Cells from the Cytotoxic Effect of Drugs with Anti-fibrotic Activity

Abstract

Background: The α and β adrenoblockers have been tested as an alternative treatment for chronic liver lesions such as fibrosis and cirrhosis in animal models, as well as their possible participation during the regeneration of the damage caused by liver cirrhosis in a hamster model. However, it was observed that doxazosin caused slight morphological changes in hepatocytes, while that curcumin showed protection to the hepatic parenchyma. Regardless, the pharmacokinetic effects of these 𝛼/𝛽 adrenoblockers on the hepatocytes' cell viability, possibly involved in the hepatic parenchyma's repopulation during cirrhosis reversal, are unknown. The present study aimed to elucidate the protective effect of curcumin on the possible side effects of doxazosin, tamsulosin, and carvedilol on the HepG2 cell line, drugs already tested with antifibrotic activity.Methods: HepG2 cells were exposed to 0.1, 0.5, 10, and 25 µM of doxazosin, carvedilol, and tamsulosin for 24, 48, and 72 h, for curcumin, cells were pretreated with 1 µM for 1 h before exposure to α and β adrenoblockers. The cell viability was assessed by MTT assay. The morphological changes were determined using hematoxylin and eosin (H&E) staining, scanning electron microscope (SEM), and acridine orange (AO) staining. Results: We observed that the doxazosin decreases cell viability dependently time and dose; carvedilol and tamsulosin increase cell proliferation. However, curcumin induces regulation of these effects in HepG2 cell line, increasing or maintaining viability compared to control. The pretreatment with curcumin regulated AST levels (aspartate aminotransferase) and ALT (alanine aminotransferase) in cells exposed to α and β adrenoblockers. The SEM and H&E staining provided evidence that doxazosin, carvedilol, and tamsulosin induced morphological changes in HepG2 cell line, depending on time and dose, approximately 80% of the cells treated with drugs were balonized, and curcumin protected these effects, maintaining the morphology in 90% of the treated cells.Conclusions: The present study demonstrates that curcumin protected the HepG2 cells against cytotoxicity and morphological changes induced by the α and β adrenoblockers attenuating secondary effects for possible oxidative stress. In this way, it is concluded that these treatments with antifibrotic effect, in co-treatment with curcumin, will not affect the possible repopulation process of the liver parenchyma during the reversion of fibrosis.

Protective Effect of Curcumin against Doxazosin- and Carvedilol-Induced Oxidative Stress in HepG2 Cells

“…Based on important antecedents of the interaction of doxazosin and carvedilol with the liver parenchyma, several stud-ies have been conducted, wherein these drugs were used to treat liver fibrosis in animal models, and morphological changes and alterations in levels of liver proliferation markers were observed [4,[9][10][11]. Recently, the morphological changes induced by these drugs in the HepG2 cells have been reported (unpublished data [12]). Based on these results, the present study was developed to analyze the effect of doxazosin or carvedilol on cytotoxicity, morphological changes, mRNA expression of antioxidant response genes, and cell death in HepG2 cells, which was used as a cell model liver.…”