The Protective Effects of Thymosin-β-4 in a Rat Model of Ischemic Acute Kidney Injury

Abstract

Background

Despite the progress in the treatment of acute kidney injury (AKI), current curative approaches fail to provide adequate treatment. In this study, we aimed to investigate the possible protective effects of thymosin-β-4(Tβ4) on an ischemic AKI model in rats.

Methods

Rats were randomly assigned into four groups (n = 8/group): The control group (sham-operated), the ischemia-reperfusion (I/R) group; renal ischemia (90 min) by infrarenal abdominal aortic occlusion followed by reperfusion (3 h), the Tβ4 + I/R group; treated with Tβ4 before I/R, and the I/Tβ4/R group; treated with Tβ4 just before reperfusion. Besides renal function determination (creatinine (Cr) and blood urea nitrogen (BUN)); histological evaluation was also conducted. Renal tissue caspase-9, matrix metalloproteinase (MMP-9) activities, and hyaluronan levels were measured. Additionally, renal tissue oxidative stress (lipid hydroperoxide, malondialdehyde, superoxide dismutase, glutathione, pro-oxidant-antioxidant balance, ferric reducing antioxidant power, nitric oxide), inflammation (tumor necrosis factor-α, interleukin-1β, interleukin-6, nuclear factor-κβ) were evaluated.

Results

I/R increased the level of caspase-9, MMP-9 activity, and hyaluronan (p < 0.001) and these were significantly decreased in both Tβ4 groups. Moreover, I/R led to increases in oxidative stress and inflammation parameters (p < 0.001) while the levels of antioxidants were decreased. Nevertheless, Tβ4 in both groups were able to restore oxidative stress and inflammation parameters. Furthermore, Tβ4 attenuated histologic injury caused by I/R (p < 0.01) and diminished serum urea-creatinine levels (p < 0.001).

Conclusion

These results suggest that Tβ4 has significant improving effects in ischemic acute kidney injury. This beneficial effect might be a result of the inhibition of extracellular matrix remodeling and apoptosis cascade via modulation in renal redox status and inflammation.

Keywords:

• thymosin-β-4
• acute kidney injury
• ischemia

Acknowledgment

Synthetic Tβ4 was gifted by RegeneRx Biopharmaceuticals in Rockville, MD USA. All of the authors have read and approved the manuscript.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Funding

This study was funded by Scientific Research Projects Coordination Unit of Istanbul University. Project number: 25214.

Author contribution

Conceptualization, G.S; Methodology, O.M.Y, I.G., G.G., G.T., A.C., S.A., M.E., I.S., H.U., N.Y, Formal Analysis, O.M.Y., I.G., F.S, N.Y, Writing—Original Draft Preparation, U.A, Writing—Review & Editing, U.A, Supervision, G.S, Interpretation of data for the work: U.A, G.S; Revising it critically for important intellectual content: UA, GS; Funding Acquisition, G.S.