Orally active, species-independent novel A3 adenosine receptor antagonist protects against kidney injury in db/db mice

• DOI: 10.1038/s12276-018-0053-x
• Publication Date: 2018-04-19T02:10:17Z
• Authors: Debra Dorotea; Ahreum Cho; Gayoung Lee; Guideock Kwon; Junghwa Lee; Pramod K. Sahu; Lak Shin Jeong; Dae Ryong Cha; Hunjoo Ha
• Keywords: Male; 0301 basic medicine; Adenosine; Dose-Response Relationship, Drug; Receptor, Adenosine A3; R; Administration, Oral; QD415-436; Kidney; Biochemistry; Article; 3. Good health; Mice; 03 medical and health sciences; Adenosine A3 Receptor Agonists; Medicine; Animals; Diabetic Nephropathies; Ureteral Obstruction

Diabetic kidney disease (DKD) is the leading cause of end-stage disease, and current pharmacological treatment for DKD limited to renin-angiotensin system (RAS) inhibitors. Adenosine detectable in significantly elevated response cellular damage. While all 4 known subtypes adenosine receptors, namely, A1AR, A2aAR, A2bAR, A3AR, are expressed kidney, our previous study has demonstrated that a novel, orally active, species-independent, selective A3AR antagonist, LJ-1888, ameliorates unilateral ureteral obstruction-induced tubulointerstitial fibrosis. The present examined protective effects LJ-2698, which higher affinity selectivity than on DKD. In experiment I, dose-dependent LJ-2698 were by administering 1.5, 5, or 10 mg/kg 12 weeks 8-week-old db/db mice. II, (10 mg/kg) compared those losartan (1.5 mg/kg), standard patients with effectively prevented injuries such as albuminuria, glomerular hypertrophy, tubular injury, podocyte fibrosis, inflammation, oxidative stress diabetic mice much losartan. addition, inhibition lipid accumulation along increases PGC1α, master regulator mitochondrial biogenesis, treated either These results suggest may become novel therapeutic agent against A targeting protein involved progression shows promise mouse trials. Between 30 40 per cent suffer from DKD, common fatal disease. Protein commonly cell surfaces throughout body, play both positive negative roles diseases. A3 receptor (A3AR) highly tissue, linked progression. Hunjoo Ha at Ewha Womans University Seoul, Republic Korea, co-workers effect drug 12-week lowered improved function. It prove an invaluable drug, particularly combination existing drug.