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

Abstract

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.

Diacerein modulates TLR4/ NF‐κB/IL‐1β and TRPC1/CHOP signalling pathways in gentamicin‐induced parotid toxicity in rats

“…Previous studies, in agreement with our data, reported the correlation of the inflammatory response to GNT in clinical and animal studies 30,31 . Karimi et al, 32 reported that GNT treatment induced a significant systemic inflammation, which may be linked to the associated increase of pro‐inflammatory chemokines and cytokines like TNF‐α and IL‐1.…”

Potential mechanisms of SARS‐CoV‐2 action on male gonadal function and fertility: Current status and future prospects

“…First, male gonadal involvement and a subsequent inflammation in testes are possible complications of SARS-CoV-2 (Fan et al, 2020;Ma et al, 2020;Ren et al, 2020;Rival et al, 2006;Xu et al, 2006). Inflammation can lead to excessive production of ROS, and this product can lead to sperm DNA damage (Anifandis et al, 2020;Evenson & Wixon, 2006;Homa et al, 2019;Karimi et al, 2020). Moreover, SARS-CoV-2 infection causes psychological stress, which is a major cause of systemic oxidative stress (Li et al, 2020).…”

Investigation of the effect of Polygonum cognatum Meissn. ethanol extract Bax, Caspase-3, Bcl-2, NF-B and NRF-2/HO-1 pathways in streptozotocin induced diabetic rats

“…Recently, it has been reported that apaptosis parameters such as Bax, Bcl-2, Caspase-3, and inflammation pathways such as NF-κB, Nrf-2 and HO-1 are affected [22,23]. The results showed the downregulation of Nrf-2 and HO-1 in the kidney of diabetic rats and revealed that this effect was prevented by PCE treatment by increasing protein expression levels.…”