Protective effect of pregabalin on renal and renal endothelial damage in sepsis induced by lipopolysaccharide

Abstract

Objective

We investigated the protective effects of pregabalin (PRG) on kidney and renal endothelial damage in sepsis induced by Lipopolysaccharide (LPS).

Materials and Methods

Rats were randomly divided into three groups as control, LPS and LPS+PRG. Saline solution was administered 30 mg/kg orally and 5 mg/kg intraperitoneally (i.p.) to the control group. LPS was applied as 5 mg/kg, i.p. to the LPS group. In the LPS+PRG group, PRG at 30 mg/kg orally and one hour before LPS administration, one hour later 5 mg/kg i.p. LPS was applied. Rats were sacrificed 6 hours after LPS administration.

Results

White Blood Cell (WBC), granulocyte, Blood Urea Nitrogen (BUN), creatinine, uric asid, Total Oxidant Status (TOS) and Oxidative Stress Index (OSI) significantly increased (p<0.05); platelets (PLT), activated partial thromboplastin time (aPTT) and Total Antioxidant Status (TAS) significantly decreased in the LPS group compared to the control group (p<0.05). In the LPS+PRG group WBC, granulocyte, BUN, creatinine, uric asid, TOS and OSI significantly decreased (p<0.05); PLT, aPTT and TAS significantly increased compared to the LPS group(p<0.05). Histopathological examinations showed that kidney and renal endothelial damage in the LPS group decreased in the LPS+PRG group. Immunohistochemically IL1-β, IL-6, IL-10, TNF-α expressions in kidney tissue and Toll-Like Receptors-4 (TLR-4) and NF-κB expressions in the renal endothelial tissue significantly increased in the LPS group compared to the control group and significantly decreased in the LPS+PRG group compared to the LPS group (p<0.001).

Conclusions

Sepsis causes kidney and renal endothelial damage and PRG reduces this damage. Therefore PRG can be used in prophylactic treatment in sepsis, supported by more studies.

Brief synopsis

In this study, kidney and renal endothelial damage in sepsis was investigated. The effect of pregabalin on kidney and renal endothelial damage in sepsis was evaluated.

Keywords:

• Kidney
• renal endothelium
• lPS
• pregabalin
• sepsis

Author contributions

All authors contributed to the study's conception and design. DÇ, RA and NG conceived and designed this study. DÇ, AY, RA and ÖÖ carried out experiments. OK, RA, ÖÖ collected and analyzed data. DÇ wrote the manuscript, which was critically reviewed and revised by RA and NG. All authors read and approved the final manuscript.

Ethical approval

Ethics committee approval was obtained for our study with the decision of Burdur Mehmet Akif Ersoy University Animal Experiments Local Ethics Committee, dated 16 October 2019 and numbered 565.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The underlying data supporting the results of our study were available on request. The corresponding author (Dilek Çevik) is contacted to request the data.

Additional information

Funding

This research received funding support from Suleyman Demirel University Scientific Research Projects Coordination Unit (Project number: TM-2019-7407).