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en Celastrol Mitigates Acetaminophen-Induced Nephrotoxicity in Rats via Targeting Renal Oxidative Stress, Inflammation, Apoptosis with Enhancement in Aquaporin 1 Level بیوشیمی Biochemistry مقالات اصلی Original Article <div style="text-align: justify;">Background: Acetaminophen also name paracetamol is a popular antipyretic and analgesic drug, in a large dose produces a cute kidney injury either in human or 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.   Conclusion: We provided a novel treatment against acetaminophen induced nephrotoxicity with targeting renal oxidative stress, inflammation, apoptosis with elevation of Aquaporin 1 (AQP1) level.  </div> Acetaminophen Apoptosis, Aquaporin 1 (AQP1), Celastrol, Inflammation, Oxidative Stress. 204 217 http://rbmb.net/browse.php?a_code=A-10-1509-1&slc_lang=en&sid=1 Mohie Mahmoud Ibrahim 100319475328460020448 100319475328460020448 No Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa, Jordan & Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Egypt. Amira Osman 100319475328460020449 100319475328460020449 No Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa, Jordan & Department of Histology and Cell Biology, Faculty of Medicine, Kafrelsheikh University, Egypt. Azza Ibrahim Helal 100319475328460020450 100319475328460020450 No Department of Histology and Cell Biology, Faculty of Medicine, Kafrelsheikh University, Egypt. Ahmed Mohsen Faheem 100319475328460020451 100319475328460020451 No Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Egypt. Mohammad Abd-El-Same'e El-Kattan 100319475328460020452 100319475328460020452 No Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Egypt. Iman Ibrahim 100319475328460020453 100319475328460020453 No Department of Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt. Ahmed Abdel-monem Elmetwally 100319475328460020454 100319475328460020454 No Clinical Pharmacology Department, Faculty of Medicine, Mansoura University, Egypt. 35516. Sara Abubakr 100319475328460020455 100319475328460020455 No Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Egypt. Alaa Mohamed Badawy 100319475328460020456 100319475328460020456 No Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Egypt. Emadeldeen Hussin emaadeldeenhamed@mans.edu.eg. 100319475328460020457 100319475328460020457 Yes Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Egypt.