Journal of Investigative Surgery (Jul 2021)

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

  • Ugur Aksu,
  • Onur M. Yaman,
  • Ibrahim Guner,
  • Gulcan Guntas,
  • Fuat Sonmez,
  • Gamze Tanriverdi,
  • Mediha Eser,
  • Aris Cakiris,
  • Sibel Akyol,
  • İsmail Seçkin,
  • Hafize Uzun,
  • Nermin Yelmen,
  • Gulderen Sahin

DOI
https://doi.org/10.1080/08941939.2019.1672841
Journal volume & issue
Vol. 34, no. 6
pp. 601 – 609

Abstract

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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.

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