Mirabegron, dependent on β3-adrenergic receptor, alleviates mercuric chloride-induced kidney injury by reversing the impact on the inflammatory network, M1/M2 macrophages, and claudin-2.

The β3-adrenergic receptor (β3-AR) agonism mirabegron is used to treat overactive urinary bladder syndrome; however, its role against acute kidney injury (AKI) is not unveiled, hence, we aim to repurpose mirabegron in the treatment of mercuric chloride (HgCl)-induced AKI. Rats were allocated into normal, normal + mirabegron, HgCl untreated, HgCl + mirabegron, and HgCl + the β3-AR blocker SR59230A + mirabegron. The latter increased the mRNA of β3-AR and miR-127 besides downregulating NF-κB p65 protein expression and the contents of its downstream targets iNOS, IL-4, -13, and -17 but increased that of IL-10 to attest its anti-inflammatory capacity.

Anandamide modulates WNT-5A/BCL-2, IP3/NFATc1, and HMGB1/NF-κB trajectories to protect against mercuric chloride-induced acute kidney injury.

Endocannabinoid anandamide (AEA) has a physiological role in regulating renal blood flow, whereas its analogs ameliorated renal ischemia/reperfusion injury. Nonetheless, the role of AEA against mercuric chloride (HgCl)-induced renal toxicity has not been unraveled. Rats were allocated into control, HgCl, and HgCl/AEA treated groups.