Indirect Bilirubin Mitigates Tubular Vacuolization and Injury in Experimental Contrast Nephropathy

Contrast media (CM) are essential in interventional cardiology and radiological imaging but may cause contrast-induced nephropathy (CIN) via inflammation, apoptosis, necrosis, vasoconstriction, oxidative stress, and cellular danger signaling. Indirect bilirubin (IB) has shown tissue-protective effects by reducing inflammation, oxidative stress, and apoptosis. Twenty-four Wistar albino rats were randomized into three groups (n = 8 each). CIN was induced in two groups using intraperitoneal indomethacin (10 mg/kg), intravenous L-NAME (10 mg/kg), and intravenous iohexol (3 g/kg). One CIN group received intraperitoneal IB (30 mg/kg in DMSO), while the other remained untreated. The sham group received vehicle only. Serum creatinine and urea increased significantly in both CIN groups versus sham (p < 0.05), accompanied by marked tubular injury and renal vacuolization. IB treatment reduced tubular damage and vacuolization significantly (p < 0.05), though reductions in creatinine and urea were not statistically significant. Unexpectedly, renal expression of cytochrome-c, IL-1β, and TNF-α was lower in untreated CIN rats compared to IB-treated CIN rats. IB appears to mitigate renal structural injury in CIN, but its effects on apoptotic and inflammatory markers remain complex. Further studies are required to clarify its mechanisms, particularly hypoxia/ischemia, vasoconstriction and cellular danger pathways etc.