Biochemical interaction of pyrvinium in gentamicin-induced acute kidney injury by modulating calcium dyshomeostasis and mitochondrial dysfunction.

Khalid Saad Alharbi, Tabinda Ali, Yogendra Singh, Ahmed Saleh Ali Al-Ghamdi, Imran Kazmi, Fahad A Al-Abbasi, Sami I Alzarea, Obaid Afzal, Abdulmalik Saleh Alfawaz Altamimi, Sachin Kumar Singh, Dinesh Kumar Chellappan, Kamal Dua, Gaurav Gupta

Journal: Chemico-biological interactions 2022;363():110020

PMID: 35750223

Full Text on Elsevier Science View on PubMed

Abstract

Acute kidney injury (AKI) has a poor clinical prognosis and increases the risk of chronic kidney failure (CKD). It is a common complication of organ failure in hospitalised patients (10-15% of all hospitalizations) and in intensive care unit (ICU) patients, with an incidence of up to 50%. Concerning ICU, AKI has a mortality rate ranging from 27% to 35%, rising to 60%-65% when dialysis is needed, with roughly 5%-20% of survivors requiring dialysis on discharge. AKI is believed to cause over 7 million deaths per year worldwide. Currently, there is no treatment for AKI or its progression to CKD. When activated by AKI, numerous pathways have been suggested as possible contributors to CKD progression. Wnt/β-catenin is a crucial regulator of kidney development that increases following the injury. Despite the overwhelming evidence that Wnt/β-catenin promotes AKI, tubulointerstitial fibrosis, a hallmark of CKD progression, is also promoted by this pathway. The therapeutic potential of Wnt/β-catenin in the treatment of AKI and the progression from AKI to CKD is being studied. This hypothesis aims to determine whether the Wnt/β-catenin inhibitor pyrvinium has a beneficial effect on the renal dysfunction and damage caused by Gentamicin.

Address: Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi Arabia.; Department of Molecular Medicine, Jamia Hamdard, New Delhi, 110062, India.; Department of Pharmacology, Maharishi Arvind College of Pharmacy, Ambabari Circle, Ambabari, Jaipur, 302023, India.; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: [email protected].; Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj, 11942, Saudi Arabia.; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia.; Department of Life Sciences, School of Pharmacy, International Medical University, Kuala Lumpur, 57000, Malaysia.; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia; Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW, 2007, Australia.; School of Pharmacy, Suresh Gyan Vihar University, Jagatpura 302017, Mahal Road, Jaipur, India; Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India. Electronic address: [email protected].

DOI: 10.1016/j.cbi.2022.110020

Link outs

Free resources

Medical:

https://medlineplus.gov/chronickidneydisease.html

Subscription / membership required

Full Text Sources:

https://linkinghub.elsevier.com/retrieve/pii/S0009...

MeSH Terms: Acute Kidney Injury, Calcium, Gentamicins, Humans, Mitochondria, Pyrvinium Compounds, Renal Insufficiency, Chronic, beta Catenin