arbutin and Chemical-and-Drug-Induced-Liver-Injury

Cyclophosphamide (CP) is a potent anticancer drug widely employed in chemotherapy against various types of cancer. However, CP leads to toxicity to non-targeted organs, including the liver and this limits its clinical use. This study explored the role of arbutin (ARB) against CP-mediated oxidative and inflammatory reactions and hepatotoxicity. Rats were administered ARB (25 and 50 mg/kg) for 14 days and CP (150 mg/kg). CP triggered liver tissue injury with marked increase in serum AST, ALT, ALP, and bilirubin, and hepatic malondialdehyde (MDA) and nitric oxide (NO) coupled with diminution of GSH, SOD, catalase, and GPx. Liver NF-kB p65, NOS, IL-6, TNF-α, Bax and caspase-3 were upregulated by CP injection and IL-10 and Bcl-2 were decreased. ARB prevented liver injury, suppressed MDA, NO, NF-kB p65, inflammatory markers, Bax and caspase-3 in CP-treated rats. ARB restored antioxidants, IL-10 and Bcl-2, and enhanced Nrf2 and hemeoxygenase-1 (HO) both gene and protein in the liver of rats. In conclusion, these results pinpointed the protective role of ARB on oxidative and inflammatory reactions, apoptosis, and hepatotoxicity in rats. This hepatoprotective activity was linked to the ability of ARB to modulate Nrf2/HO-1 pathway.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antioxidants; Arbutin; bcl-2-Associated X Protein; Caspase 3; Chemical and Drug Induced Liver Injury; Cyclophosphamide; Inflammation; Interleukin-10; Liver; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Rats; Signal Transduction

Topics: Acetaminophen; Animals; Antioxidants; Arbutin; Caffeic Acids; Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liver Injury, Chronic; Liver; Mice; Molecular Docking Simulation; NF-E2-Related Factor 2; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Signal Transduction; Tea

Alcoholic liver disease (ALD) is a pervasive ailment due to the excessive consumption of alcohol and there is no operative drug for its treatment. The current exploration was intended to examine the hepatoprotective efficacy of arbutin against ethanol-provoked liver injury in rats via the modulation of the Nrf-2/HO-1 signaling cascade. Wistar rats were challenged with the 3 g/kg/day (40% v/v) of ethanol for 4 weeks to provoke the ALD and concomitantly supplemented with 40 mg/kg of arbutin. The liver function markers enzymes, inflammatory cytokines, and oxidative stress markers levels were scrutinized by using the respective assay kits. The mRNA expression of Nrf-2/HO-1 signaling proteins was studied by reverse-transcription polymerase chain reaction. The histological alterations of liver tissues were examined. HepG2 cells were used for the in vitro studies. The levels of oxidative stress markers and liver marker enzymes were examined by using kits. Reactive oxygen species (ROS) and apoptotic cell death was detected by using fluorescent staining. There were no major differences in the body weight and liver weight of experimental animals. Arbutin treatment appreciably reduced the liver marker enzymes, upregulated superoxide dismutase, glutathione peroxidase, total antioxidant capacity, and the hydroxyl scavenging ability, and diminished the tumor necrosis factor-α and interleukin-6 levels in the serum of ethanol provoked animals. Arbutin triggered Nrf-2/HO-1 signaling cascade liver tissues of ethanol-provoked animals. Histological findings proved the preventing effects of arbutin. Arbutin did not demonstrate toxicity to the HepG2 cells. It reduced the aspartate aminotransferase and alanine aminotransferase, ROS, apoptotic cell death, lipid peroxidation and improved the antioxidants' levels in the ethanol-challenged HepG2 cells. In conclusion, our findings unveiled the hepatoprotective efficacy of arbutin against ethanol-provoked liver injury in rats. It could be a promising agent to treat alcoholic liver disease in the future.

Topics: Alanine Transaminase; Animals; Antioxidants; Apoptosis; Arbutin; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Cytokines; Disease Models, Animal; Ethanol; Heme Oxygenase (Decyclizing); Hep G2 Cells; Humans; Lipid Peroxidation; Liver Diseases, Alcoholic; NF-E2-Related Factor 2; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Signal Transduction