Investigation of Analgesic Minimum Effective Dose of Apelin‐13 With Different Doses of Intraperitoneal Injections and its Effects on Kidney Tissue
Authors: Dursun Ali Doğan , Ozdemir Cagri , Sezen Saban Cem , Kucuk Aysegul , Arslan Mustafa 
Published: April 2020

Background and Aims

Apelin and APJ form a signaling pathway and are widely expressed in a variety of tissues including the heart, kidney and vessels. Apelin and APJ have various effects in many systems such as regulation of blood pressure and vascular tone, cardiac contractility, nociception, heart rate, apoptosis, inflammation. Apelin‐13 has a potential analgesic and proanalgesic effect, although the sites of analgesic effects are uncertain and controversial in terms of results. The fact that apelin can be used as a protective and therapeutic agent in the future will make important contributions both for human health and economically. The aim of the study is to investigate the analgesic minimum effective dose of Apelin‐13 with different doses of intraperitoneal application and its effects on kidney tissue.

Methods

Thirty Wistar Albino male rats were randomly divided into 5 groups. Rats were designated as control, Apelin‐25, Apelin‐50, Apelin‐100 and Apelin‐200 groups. Apelin‐13 was administered intraperitoneally at 25, 50, 100 and 200 μg/kg doses. The same volume of saline was administered intraperitoneally to the control group. Hot plate test was performed to evaluate analgesic efficacy at 0 and 30 minutes, 1 and 2 hours after administration. All rats were euthanized 24 hours after administration by intraperitoneal ketamine 100 mg/kg. Renal tissues were removed without traumatization and sent to the laboratory for evaluation of histological and oxidant status.

Results

In the hot plate test, application of apelin 50 μg/kg and above had significantly more analgesic effects than the control group. 25 μg/kg apelin application was found to have no analgesic effect. When kidney tissues were examined, at the doses of 200 μg/kg Apelin; vascular vacuolization and hypertrophy, bowman dilatation and tubular cell shedding were significantly increased but not at the control group, 25 and 50 μg/kg Apelin groups (Figure
1–
2). When the oxidative status was evaluated with TAS and TOS, 200 μg/kg Apelin increased the oxidant parameters while reducing the antioxidant parameters. There was no significant change below this dose. It was also correlated with histopathological findings.

Conclusion

That seems to be the first study on the analgesic effects of apelin in different doses in the literatüre and 50 μg/kg apelin is the minimum analgesic effective dose. The administration of 200 μg/kg apelin‐13 adversely affected kidney tissue histologically and tissue oxidative stress parameters increase by the high doses. Other aspects of these findings, including clinical significance and practical applications, merit further experimental and clinical investigation.

Support or Funding Information

This study was conducted in the GUDAM Laboratory of Gazi University with the consent of Experimental Animals Ethics Committee of Gazi University with the code G.U.ET‐19.024. The study was supported by Gazi University Scientific Research Committee (Scientific Research Project No. 01/2019‐44).

Control group, renal tissue (10X H&E)

Figure 1

200 μg/kg application of Apelin 13 increased vascular vacuolization and hypertrophy, bowman dilatation and tubular cell shedding (10X H&E)

Figure 2