دورية أكاديمية
أعرض في EDS

Unraveling the Nephroprotective Potential of Papaverine against Cisplatin Toxicity through Mitigating Oxidative Stress and Inflammation: Insights from In Silico, In Vitro, and In Vivo Investigations.

التفاصيل البيبلوغرافية
العنوان: Unraveling the Nephroprotective Potential of Papaverine against Cisplatin Toxicity through Mitigating Oxidative Stress and Inflammation: Insights from In Silico, In Vitro, and In Vivo Investigations.
المؤلفون: Abass SA; Department of Biochemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt., Elgazar AA; Department of Pharmacognosy, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt., El-Kholy SS; Department of Physiology, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt., El-Refaiy AI; Department of Agricultural Zoology and Nematology, Faculty of Agriculture (Girls), Al-Azhar University, Cairo 11884, Egypt., Nawaya RA; Department of Biochemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt., Bhat MA; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Farrag FA; Department of Anatomy, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt., Hamdi A; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt., Balaha M; Department of Medical, Oral and Biotechnological Sciences, 'G. d'Annunzio' University of Chieti-Pescara, Via dei vestini, 31-66100 Chieti, Italy., El-Magd MA; Department of Anatomy, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
المصدر: Molecules (Basel, Switzerland) [Molecules] 2024 Apr 23; Vol. 29 (9). Date of Electronic Publication: 2024 Apr 23.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, c1995-
مواضيع طبية MeSH: Cisplatin*/adverse effects , Papaverine*/pharmacology , Oxidative Stress*/drug effects , Inflammation*/drug therapy , Inflammation*/metabolism , Inflammation*/chemically induced, Animals ; Rats ; Humans ; Kidney/drug effects ; Kidney/pathology ; Kidney/metabolism ; Male ; Apoptosis/drug effects ; Antineoplastic Agents/pharmacology ; Protective Agents/pharmacology ; Antioxidants/pharmacology ; Cytokines/metabolism ; Computer Simulation ; Biomarkers
مستخلص: Cisplatin is a potent compound in anti-tumor chemotherapy; however, its clinical utility is hampered by dose-limiting nephrotoxicity. This study investigated whether papaverine could mitigate cisplatin-induced kidney damage while preserving its chemotherapeutic efficacy. Integrative bioinformatics analysis predicted papaverine modulation of the mechanistic pathways related to cisplatin renal toxicity; notably, mitogen-activated protein kinase 1 (MAPK1) signaling. We validated protective effects in normal kidney cells without interfering with cisplatin cytotoxicity on a cancer cell line. Concurrent in vivo administration of papaverine alongside cisplatin in rats prevented elevations in nephrotoxicity markers, including serum creatinine, blood urea nitrogen, and renal oxidative stress markers (malondialdehyde, inducible nitric oxide synthase (iNOS), and pro-inflammatory cytokines), as tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6). Papaverine also reduced apoptosis markers such as Bcl2 and Bcl-2-associated X protein (Bax) and kidney injury molecule-1 (KIM-1), and histological damage. In addition, it upregulates antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) while boosting anti-inflammatory signaling interleukin-10 (IL-10). These effects were underlined by the ability of Papaverine to downregulate MAPK-1 expression. Overall, these findings show papaverine could protect against cisplatin kidney damage without reducing its cytotoxic activity. Further research would allow the transition of these results to clinical practice.
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فهرسة مساهمة: Keywords: cisplatin; drug repurposing papaverine; inflammation; nephrotoxicity; network pharmacology
المشرفين على المادة: Q20Q21Q62J (Cisplatin)
DAA13NKG2Q (Papaverine)
0 (Antineoplastic Agents)
0 (Protective Agents)
0 (Antioxidants)
0 (Cytokines)
0 (Biomarkers)
تواريخ الأحداث: Date Created: 20240511 Date Completed: 20240511 Latest Revision: 20240514
رمز التحديث: 20240514
مُعرف محوري في PubMed: PMC11085772
DOI: 10.3390/molecules29091927
PMID: 38731418
قاعدة البيانات: MEDLINE
الوصف
تدمد:1420-3049
DOI:10.3390/molecules29091927