# The protein kinase 2 inhibitor tetrabromobenzotriazole protects against renal ischemia reperfusion injury

## TL;DR

This study shows that inhibiting the protein kinase CK2α with tetrabromobenzotriazole protects the kidneys from injury caused by ischemia and reperfusion.

## Contribution

The study demonstrates that CK2α inhibition reduces kidney damage during ischemia reperfusion injury through suppression of inflammatory and apoptotic pathways.

## Key findings

- TBBt pretreatment reduced markers of kidney injury, inflammation, and oxidative stress in mice.
- CK2α inhibition suppressed NF-κB and MAPK pathways, which are involved in inflammation and cell death.
- Emodin, another CK2α inhibitor, also showed similar renoprotective effects.

## Abstract

Protein kinase 2 (CK2) activation was reported to enhance reactive oxygen species production and activate the nuclear factor κB (NF-κB) pathway. Because oxidative stress and inflammation are critical events for tissue destruction during ischemia reperfusion (I/R), we sought to determine whether CK2 was important in the renal response to I/R. Mice underwent 25 min of renal ischemia and were then reperfused. We confirmed an increased expression of CK2α during the reperfusion period, while expression of CK2β remained consistent. We administered tetrabromobenzotriazole (TBBt), a selective CK2α inhibitor before inducing I/R injury. Mice subjected to I/R injury showed typical patterns of acute kidney injury; blood urea nitrogen and serum creatinine levels, tubular necrosis and apoptosis, inflammatory cell infiltration and proinflammatory cytokine production, and oxidative stress were markedly increased when compared to sham mice. However, pretreatment with TBBt abolished these changes and improved renal function and architecture. Similar renoprotective effects of CK2α inhibition were observed for emodin. Renoprotective effects of CK2α inhibition were associated with suppression of NF-κB and mitogen activated protein kinase (MAPK) pathways. Taken together, these results suggest that CK2α mediates proapoptotic and proinflammatory signaling, thus the CK2α inhibitor may be used to prevent renal I/R injuries observed in clinical settings.