Tissue & cell · 2026
Enhanced hepatoprotective effect of Phoenix dactylifera L. and carvedilol in dexamethasone-induced toxicity in rats by reducing oxidative stress and apoptosis: possible role of Hotair-1/mir-148a pathway.
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Mohamed Rasha M S M, Hassan Nancy Husseiny, El-Sayed Sherein F, Shawky Salma A, El-Feky Hoda K, Sakr Samar, Mohamed Eman Abdelsalam, Fayad Esraa H, Abdulla Doaa M, Amin Mohammed Ahmed Shehata, Kaoud Amira Abd Elazim
Аннотация
BACKGROUND: Corticosteroid toxicity can predispose individuals to metabolic dysfunction-associated steatotic liver disease (MASLD), which may progress to metabolic dysfunction-associated steatohepatitis (MASH). Date palm fruit (Phoenix dactylifera L.) is widely recognized as a nutraceutical due to its rich content of bioactive phytochemical compounds.
OBJECTIVES: This study aimed to investigate the enhanced hepatoprotective effects of date palm fruit (pulp and ethanolic extract) in comparison with carvedilol, as well as their combined effects, in a model of dexamethasone-induced hepatotoxicity.
METHODS: Seven experimental groups were included: control; dexamethasone (10 mg/kg/day, s.c.); carvedilol (30 mg/kg/day, oral); date palm fruit pulp (1:2 mixed with chow diet, oral); date palm fruit extract (300 mg/kg/day, oral); and their respective combinations. Treatments were administered for 3 weeks, starting 2 weeks prior to dexamethasone exposure.
RESULTS: Dexamethasone administration induced hepatomegaly, elevated serum transaminases (ALT and AST), and oxidative stress, as evidenced by decreased superoxide dismutase (SOD) and reduced glutathione (GSH) levels, along with increased malondialdehyde (MDA). It also activated apoptotic pathways (caspase-3, Bcl-2 dysregulation) and disrupted the HOTAIR-1/miR-148a axis, accompanied by marked histopathological alterations and fibrosis. Treatment with date palm fruit pulp, extract, and carvedilol conferred hepatoprotective effects, with the combination therapy demonstrating superior efficacy.
CONCLUSION: These findings highlight the therapeutic potential of integrating natural antioxidants with pharmacological agents to mitigate drug-induced hepatotoxicity.
OBJECTIVES: This study aimed to investigate the enhanced hepatoprotective effects of date palm fruit (pulp and ethanolic extract) in comparison with carvedilol, as well as their combined effects, in a model of dexamethasone-induced hepatotoxicity.
METHODS: Seven experimental groups were included: control; dexamethasone (10 mg/kg/day, s.c.); carvedilol (30 mg/kg/day, oral); date palm fruit pulp (1:2 mixed with chow diet, oral); date palm fruit extract (300 mg/kg/day, oral); and their respective combinations. Treatments were administered for 3 weeks, starting 2 weeks prior to dexamethasone exposure.
RESULTS: Dexamethasone administration induced hepatomegaly, elevated serum transaminases (ALT and AST), and oxidative stress, as evidenced by decreased superoxide dismutase (SOD) and reduced glutathione (GSH) levels, along with increased malondialdehyde (MDA). It also activated apoptotic pathways (caspase-3, Bcl-2 dysregulation) and disrupted the HOTAIR-1/miR-148a axis, accompanied by marked histopathological alterations and fibrosis. Treatment with date palm fruit pulp, extract, and carvedilol conferred hepatoprotective effects, with the combination therapy demonstrating superior efficacy.
CONCLUSION: These findings highlight the therapeutic potential of integrating natural antioxidants with pharmacological agents to mitigate drug-induced hepatotoxicity.