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Azithromycin Mitigates Cisplatin-Induced Lung Oxidative Stress, Inflammation and Necroptosis by Upregulating SIRT1, PPARγ, and Nrf2/HO-1 Signaling.
Hassanein, Emad H M; Sayed, Ghadir A; Alzoghaibi, Abdullah M; Alammar, Abdalmohsen S; Abdel-Wahab, Basel A; Abd El-Ghafar, Omnia A M; Mahdi, Somya E; Atwa, Ahmed M; Alzoghaibi, Mohammed A; Mahmoud, Ayman M.
  • Hassanein EHM; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt.
  • Sayed GA; Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, Egypt.
  • Alzoghaibi AM; College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia.
  • Alammar AS; Dental Department, Hail Health Cluster, Ministry of Health, Hail 55421, Saudi Arabia.
  • Abdel-Wahab BA; Department of Medical Pharmacology, College of Medicine, Assiut University, Assiut 71515, Egypt.
  • Abd El-Ghafar OAM; Department of Pharmacology, College of Pharmacy, Najran University, Najran 55461, Saudi Arabia.
  • Mahdi SE; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef 62521, Egypt.
  • Atwa AM; Department of Physiology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt.
  • Alzoghaibi MA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, Egypt.
  • Mahmoud AM; Physiology Department, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia.
Pharmaceuticals (Basel) ; 16(1)2022 Dec 29.
Article in English | MEDLINE | ID: covidwho-2216693
ABSTRACT
Acute lung injury (ALI) is one of the adverse effects of the antineoplastic agent cisplatin (CIS). Oxidative stress, inflammation, and necroptosis are linked to the emergence of lung injury in various disorders. This study evaluated the effect of the macrolide antibiotic azithromycin (AZM) on oxidative stress, inflammatory response, and necroptosis in the lungs of CIS-administered rats, pinpointing the involvement of PPARγ, SIRT1, and Nrf2/HO-1 signaling. The rats received AZM for 10 days and a single dose of CIS on the 7th day. CIS provoked bronchial and alveolar injury along with increased levels of ROS, MDA, NO, MPO, NF-κB p65, TNF-α, and IL-1ß, and decreased levels of GSH, SOD, GST, and IL-10, denoting oxidative and inflammatory responses. The necroptosis-related proteins RIP1, RIP3, MLKL, and caspase-8 were upregulated in CIS-treated rats. AZM effectively prevented lung tissue injury, ameliorated oxidative stress and NF-κB p65 and pro-inflammatory markers levels, boosted antioxidants and IL-10, and downregulated necroptosis-related proteins in CIS-administered rats. AZM decreased the concentration of Ang II and increased those of Ang (1-7), cytoglobin, PPARγ, SIRT1, Nrf2, and HO-1 in the lungs of CIS-treated rats. In conclusion, AZM attenuated the lung injury provoked by CIS in rats through the suppression of inflammation, oxidative stress, and necroptosis. The protective effect of AZM was associated with the upregulation of Nrf2/HO-1 signaling, cytoglobin, PPARγ, and SIRT1.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies Topics: Vaccines Language: English Year: 2022 Document Type: Article Affiliation country: Ph16010052

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies Topics: Vaccines Language: English Year: 2022 Document Type: Article Affiliation country: Ph16010052