Toll‐like receptor‐2 mediates systemic inflammation in gentamicin‐induced rat nephrotoxicity

• Published in: Clinical and experimental pharmacology & physiology 2020-09, Vol.47 (9), p.1584-1590
• Main Authors: Karimi, Zeinab, Pakfetrat, Zahra, Roozbeh, Jamshid, Janfeshan, Sahar
• Format: Article
• Language: English
• Subjects: Adaptive systems; aminoglycoside; Aminoglycoside antibiotics; Aminoglycosides; Antibiotics; Blood; Buffy coat; Chemokines; Creatinine; Cytokines; Enlargement; Gene expression; Gentamicin; Immune system; Inflammation; Interleukins; Kidneys; Monocytes; Proteins; Receptors; Serum levels; Structure-function relationships; Tissues; TLR2 protein; Toll-like receptors; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumors; Urea
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.13334

Gentamicin is an aminoglycoside antibiotic commonly administrated to patients with Gram‐negative infections. Gentamicin induced nephrotoxicity by functional and structural impairment. Toll‐like receptors (TLRs) as key mediators in the innate and adaptive immune system response involved in gentamicin‐induced nephrotoxicity. The present study aimed to investigate the gene expression of TLR2 and pro‐inflammatory cytokines in the renal tissues and buffy coat of the whole blood in gentamicin‐treated rats. Twenty adult male Sprague Dawley rats weighing 180–200 were randomly divided into gentamicin (100 mg/kg, i.p) and control groups (n = 10). After 10 days, the serum creatinine (Cr) levels and blood urea nitrogen (BUN) were measured. The mRNA levels of TLR2, tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β, and monocyte chemoattractant peptide (MCP)‐1 were investigated in the renal tissue and buffy coat by qRT‐PCR. Kidney histological analysis performed by hematoxylin‐eosin (H&E) staining. Functional disturbance is characterized by a significant increase in the serum levels of Cr and BUN in the gentamicin group. Renal tissue slides of the gentamicin group indicated severe glomerular and tubular damage including lobulation of the glomerular tuft, Bowman's space enlargement, acute tubular necrosis, and proximal tubular destruction. The mRNA levels of IL‐1β, TNF‐α, MCP‐1, and TLR2 increased in the buffy coat, but all of them except TLR2 decreased in the renal tissues in the gentamicin group compared with controls. Gentamicin administration induced relative systemic inflammation, which may be related to an increase in the mRNA levels of TLR2 results in gene expression of pro‐inflammatory chemokines and cytokines including IL‐1β, TNF‐α, and MCP‐1 in immune cells.