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

Abstract

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 μM curcumin for 1 h, HepG2 cells were exposed to 0.1–25 μM 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 μM 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.

The α‐1 Adrenergic Receptor Antagonist Doxazosin Attenuates Liver Fibrosis by Alleviating Sinusoidal Capillarization and Liver Angiogenesis

“…As shown by previous studies, the level of toxicity caused by doxazosin in cells varies from cell to cell. For example, HepG2 cell viability remained about 80% after treatment with 15 µ m doxazosin for 24 h, whereas about 60% of the HepG2 cells lost vitality after treatment with 25 µ m doxazosin for 24 h. [ 34 ] Similarly, after treatment with 30 µ m doxazosin for 24 h, about 78% of the PC‐3 cells were viable. [ 17 ] In this study, we examined the pharmacotoxicity of doxazosin in HUVECs and HHSECs and found that the drug toxicity increased with increasing concentrations of doxazosin.…”

Curcumin Supplementation Improves Growth Performance and Anticoccidial Index by Improving the Antioxidant Capacity, Inhibiting Inflammatory Responses, and Maintaining Intestinal Barrier Function in Eimeria tenella-Infected Broilers

“…Curcumin has often been reported to exhibit a direct antioxidant capacity, which can relieve oxidative stress by scavenging ROS [32,33]. These could be attributed to the chemical structure of curcumin; a lipophilic polyphenol with a conjugated double bond serves as a powerful electron donor to inhibit the redox processes that produce ROS [34,35]. Thus, curcumin could improve the antioxidant capacity of broiler chickens infected with Coccidioides and maintain the equilibrium of the antioxidant enzyme system.…”