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Background: Diclofenac (DF) is a non-steroidal anti-inflammatory drug (NSAID) generally prescribed for the treatment of pain. In spite of the widespread use of DF, hepatotoxicity has been reported after its administration. The current study discloses new evidence as regards of the curative effects of chrysin (CHR) on DF-induced hepatotoxicity by regulating oxidative stress, apoptosis, autophagy, and endoplasmic reticulum (ER) stress., Methods: The animals were separated into five different groups. Group-I was in control. Group-II received CHR-only (50 mg/kg bw, p.o.) on all 5 days. Group-III received DF-only (50 mg/kg bw, i.p.) on 4th and 5th day. Group-IV received DF (50 mg/kg bw) + CHR (25 mg/kg, bw) and group-V received DF (50 mg/kg, bw) + CHR (50 mg/kg, bw) for 5 days., Results: DF injection was associated with increased MDA while reduced GSH level, activities of superoxide dismutase, glutathione peroxidase, and catalase and mRNA levels of HO-1 and Nrf2 in the liver. DF injection caused apoptosis and autophagy in the liver by up-regulating caspase-3, Bax, LC3A, and LC3B levels and down-regulating Bcl-2. DF also caused ER stress by increasing mRNA transcript levels of ATF-6, IRE1, PERK, and GRP78. Additionally, it was observed that DF administration up-regulated MMP2 and MMP9. However, treatment with CHR at a dose of 25 and 50 mg/kg considerably ameliorated oxidative stress, apoptosis, autophagy, and ER stress in liver tissue., Conclusion: Overall, the data of this study indicate that liver damage associated with DF toxicity could be ameliorated by CHR administration., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Diclofenac (Dic) was shown to increase in reactive oxygen species (ROS) levels thereby resulting oxidative stress and apoptotic cell death in colon cancer. The antioxidants can prevent and repair oxidative damage caused by ROS. The aim of this study was to assess the effect of chrysin (Chr) on Dic-induced toxicity in HT-29 and molecular mechanisms underlying its effect., Methods: Cell proliferation and cytotoxicity assays were carried out by WST-1 and LDH leakage assay, apoptotic index was calculated by TUNEL Assay, antioxidant parameters were studied by measurement of ROS, LPO and TAS levels and catalase activity, expression of caspase-3 protein levels were analyzed by immunohistochemical staining, mRNA levels of apoptotic and anti-apoptotic genes were studied by qRT-PCR., Results: The cellular processes of Dic-triggered cell death was associated with increase in ROS, malondialdehyde levels and lactate dehydrogenase release, decrease in total antioxidant and catalase activity while pretreatment with Chr reversed these effects. The expression level of p53 , cas-3 , cas-8 , Bax and cytochrome c increased in Dic-exposed group while they were reduced by Chr., Conclusion: The use of antioxidant nutritional supplements, and in particular of Chr, may reduce the efficacy of Dic in inducing apoptosis of colon cancer cells.