Protective Effects Of A Lipid Transfer Protein Isolated from Morinda citrifolia Seeds in Gentamicin-Induced Nephrotoxici
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ORIGINAL ARTICLE
Protective Effects Of A Lipid Transfer Protein Isolated from Morinda citrifolia Seeds in Gentamicin-Induced Nephrotoxicity in Rats Aline D. Marinho 1 & João A. M. Silveira 1 & Adriano J. M. Chaves-Filho 1 & Danielle S. Macedo 1 & Luana D. Carmo 1 & Nylane M. N. Alencar 1 & Pedro H. S. Costa 1 & Pedro L. Lopes 1 & Francisco A. Nogueira-Junior 1 & Natacha T. Q. Alves 1 & Francisco A. F. Xavier-Junior 2 & Janaina S. A. M. Evangelista 2 & Tiago L. Sampaio 1 & Alice M. C. Martins 1 & Dyély C. O. Campos 3 & Hermógenes D. Oliveira 3 & Roberta J. B. Jorge 1 & Helena S. A. Monteiro 1 Received: 20 February 2020 / Accepted: 14 August 2020 # Sociedade Brasileira de Farmacognosia 2020
Abstract Gentamicin is an aminoglycoside antibiotic used in the treatment of gram-negative bacterial infections. However, its prolonged use is limited due to a high risk of nephrotoxicity. This study aimed to investigate the protective effects of a lipid transfer protein isolated from Morinda citrifolia L., Rubiaceae, seeds against gentamicin-induced nephrotoxicity in rats, and in a proximal tubular epithelial cell line from Rhesus monkey (LLC-MK2). Treatment with 6.25–25 μg/ml of the protein protected cells against cytotoxicity induced by 2 mM gentamicin. In the in vivo study, protein treatment (8 mg/kg, orally administered daily for 7 days 2 h after intraperitoneal injection of 100 mg/kg gentamicin) improved the levels of creatinine, urea, and uric acid. Additionally, it alleviated oxidative stress and inflammation induced by gentamicin, including a reduction in myeloperoxidase activity and cytokine modulation. Data were corroborated with histological analysis showing attenuated alterations by protein treatment. These findings suggest that this protein protects against gentamicin-induced nephrotoxicity. In addition, this natural product may be as an adjunctive tool to reduce kidney toxicity and improve the clinical usage profile of gentamicin. Keywords Acute kidney injury . Aminoglycoside . Renal protection . Oxidative stress . Cytokines
Introduction Acute kidney injury (AKI) is a pathological complication characterized by a sudden decline in renal function (Kaddourah et al. 2017). Despite advances in medical care, AKI remains associated with increased hospitalization time and high morbidity and mortality rates, requiring meaningful therapeutic interventions that increase healthcare costs (Crews et al. 2019). Approximately 20% of hospitalized patients are diagnosed with AKI,
* João A. M. Silveira [email protected] 1
Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil
2
Faculdade de Veterinária, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil
3
Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil
partially due to ischemic, toxic, septic, or obstructive upsets. In this context, it is well established that several drugs used in clinical practice, such as contrast agents and non-steroidal
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