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Celastrol Mitigates Acetaminophen-Induced Nephrotoxicity in Rats via Targeting Renal Oxidative Stress, Inflammation,
Mohie Mahmoud Ibrahim1,2, Amira Osman1,3, Azza Ibrahim Helal3
1Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa, Jordan.
Background:
Acetaminophen also name paracetamol is apopular antipyretic and analgesic drug, in alarge doses produces a cute kidney injury either in human and animals. The aim of this study to assess the effect of celastrol in reducing acetaminophen-induced nephrotoxicity and to elucidate its underlying mechanisms.
Methods:
Rats were divided into four groups: control, celastrol-treated, acetaminophen-exposed, and a group receiving both acetaminophen and celastrol. After 24 hours, blood samples were taken and kidney tissues were harvested for histological and molecular analyses. The findings shed light on the protective effects of celastrol against acetaminophen-induced nephrotoxicity, offering insights into its therapeutic potential.
Results:
paracetamol oral intake altered renal histology with significantly P< 0.05 increased serum creatinine, blood urea nitrogen (BUN), and homogenate malonaldhyde (MDA), and immunoexpression of tumor necrosis- alpha (TNF-α), interleukin-6 (IL-6), caspase-3, Bcl-2-associated X- protein (Bax). Furthermore, it decreases homogenate level of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2), and haem oxygenase-1 (HO-1). Meanwhile, intraperitoneal injection of celastrol with acetaminophen reaffirms the previous results.
Conclusions:
We provided a novel treatment against acetaminophen induced-nephrotoxicity with targeting renal oxidative stress, inflammation, apoptosis with elevation of Aquaporin 1 (AQP1) level.
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