The role of Garcinol in abrogating cyclophosphamide/radiation nephrotoxicity via suppressing Mincle/Syk/NF-kappa B signaling pathway

Radiation and chemotherapy are toxic agents; their clinical utility, nevertheless, and curative effect are restricted by toxic side consequences such as nephrotoxicity. This study aims to determine the potential protective effects of Garcinol (G) (10 mg/kg/orally/daily for 4 weeks), a natural polyisoprenylated benzophenone, against renal injury in cyclophosphamide (CA) (150 mg/kg i.p. single-dose) and/or radiation (R) delivered as fractionated doses of 2 Gy/week up to total cumulative dose of 6 Gy to induce toxicity in rats. Kidney injury has been examined by histopathological investigation. Garcinol treatment showed amelioration by a significant decrease in the inflammatory markers (IL-1 beta and IL-6). Similarly, Garcinol-injected rats exhibited a significant decline in monocyte chemotactic protein-1(MCP-1), macrophage inducible c type lectin (Mincle), spleen tyrosine kinase (Syk), transcriptional factor (NF-kB), and toll-like receptor (TLR-4) compared to the CA + R group. Additionally, histopathological and immunohistochemical examination showed that the administration of CA and/or gamma-irradiated rats induced severe injury in kidney, and a decrease in Cyclin d1 immunostain level compared to the control group. Finally, this work may verify the protective role of Garcinol significantly shielding the kidney from damage by inhibiting Mincle expression, which also promotes M1 to M2, and prevents Syk and TLR-4/NF-kB activation.