Low dose γ irradiation promotes the protective potential of Syzgium aromaticum flower buds extract in cisplatin-mediated nephrotoxicity via regulating Nrf-2/HO-1 and NF-κB/MAPK signaling pathways

Nephrotoxicity is severe complication of cisplatin-based chemotherapy and associated with high mortality rate. This study estimates the renoprotective potential of Syzygium aromaticum L. (clove) flower bud's ethanol extract in cisplatin-induced nephrotoxicity with comprehensive chemical investigation, while exploring whether low dose γ radiation (LDR) enhances clove's nephroprotective efficacy. Determination of natural pigment content outlined that the total content was 112.22 mg/g, whereas β-carotene dominates by (41.385 mg/g). The LC-ESI-MS results guaranteed presence of 80 compounds, 39 were identified through negative ionization and 41 compounds from positive ionization belonging to diverse classes and some were first noted from the species in this study. Rats were allocated into 5 groups; control, cisplatin (7.5 mg/kg, i.p), clove (500 mg/kg, p.o), LDR (0.5 Gy) and Clove + LDR. Data revealed that clove reduced serum creatinine, urea and uric acid levels and decreased renal contents of malondialdehyde, 8-hydroxy-2'-deoxyguanosine and total oxidant status and elevated total antioxidant status. Furthermore, clove down-regulated tumor necrosis factor-α and interleukin-1β levels and suppressed gene expression of monocyte chemoattractant protein-1. Clove triggered protein expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1, whereas, it inhibited renal expression of nuclear factor kappa β and mitogen-activated protein kinase. Interestingly, the nephroprotective effect of clove + LDR was superior to clove alone as this combination effectively restored alterations in nephrotoxic markers, oxidative stress indicators, inflammatory mediators, and nephrohistoarchitecture. Dual therapy of clove and LDR could be promising method for preventing cisplatin-nephrotoxicity and potentially enhancing the therapeutic index of cisplatin.