Tests thymosin β4 for protection against ischemic acute kidney injury (AKI) in a rat renal ischemia-reperfusion model. TB4 treatment (IP injection) significantly reduced serum creatinine and BUN (kidney function markers), decreased tubular necrosis and apoptosis histologically, and lowered oxidative stress markers compared to untreated I/R controls. TB4 preserved renal architecture and function. Establishes TB4's renoprotective efficacy in the most clinically relevant model of AKI—relevant for surgical and transplant nephrology.
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 ( 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 ( 0.001) and these were significantly decreased in both Tβ4 groups. Moreover, I/R led to increases in oxidative stress and inflammation parameters ( 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 ( 0.01) and diminished serum urea-creatinine levels ( 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.