Punicalagin prevents cisplatin-induced nephrotoxicity by attenuating oxidative stress, inflammatory response, and apoptosis in rats. 2021

Saleem H Aladaileh, and Farhan K Al-Swailmi, and Mohammad H Abukhalil, and Ahmad F Ahmeda, and Ayman M Mahmoud
Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al-Batin, Saudi Arabia; Department of Medical Analysis, Princess Aisha Bint Al-Hussein College of Nursing and Health Sciences, Al-Hussein Bin Talal University, Jordan.

Nephrotoxicity is a major complication that limits the therapeutic application of cisplatin (CIS). Oxidative stress and inflammation are implicated in CIS-induced acute kidney injury (AKI) and apoptotic cell death. Punicalagin (PUN), a polyphenol in pomegranate, possesses promising anti-inflammatory and antioxidant activities, and its beneficial effect against CIS-induced AKI has not been fully elucidated. This investigation evaluated the protective effect of PUN against CIS-induced renal oxidative stress, inflammation and cell death. Rats received PUN (25 and 50 mg/kg) for 10 days and a single injection of CIS at day 7. The results showed increased serum urea and creatinine and several histopathological alterations in the kidney of CIS-intoxicated rats. Renal malondialdehyde (MDA) and nitric oxide (NO) were increased, and reduced glutathione, superoxide dismutase and catalase were declined in rats treated with CIS. PUN effectively ameliorated kidney function and attenuated tissue injury induced by CIS, decreased MDA and NO, and enhanced antioxidant defenses. Additionally, PUN downregulated NF-κB p65, iNOS, TNF-α, IL-6 and IL-1β in the kidney of rats that received CIS. Bax and caspase-3 were increased, and Bcl-2 was decreased in the kidney of CIS-intoxicated rats, an effect that was reversed by PUN. PUN upregulated Nrf2 expression in the kidney of CIS-intoxicated rats. In conclusion, PUN prevents CIS-induced AKI in rats by attenuating oxidative stress, inflammatory response and apoptosis, and upregulating Nrf2 and antioxidants.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008297 Male Males
D008315 Malondialdehyde The dialdehyde of malonic acid. Malonaldehyde,Propanedial,Malonylaldehyde,Malonyldialdehyde,Sodium Malondialdehyde,Malondialdehyde, Sodium
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D001806 Blood Urea Nitrogen The urea concentration of the blood stated in terms of nitrogen content. Serum (plasma) urea nitrogen is approximately 12% higher than blood urea nitrogen concentration because of the greater protein content of red blood cells. Increases in blood or serum urea nitrogen are referred to as azotemia and may have prerenal, renal, or postrenal causes. (From Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984) BUN,Nitrogen, Blood Urea,Urea Nitrogen, Blood
D002374 Catalase An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA. Catalase A,Catalase T,Manganese Catalase,Mn Catalase
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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