Ameliorative effect of desloratadine against cisplatin-induced renal and testicular toxicity in rats: Attention to TLR4/NLRP3 inflammasome signaling pathway.

ABSTRACT

Cisplatin (CIS) is a potent anticancer drug that is used in the treatment of different types of cancer. Owing to its serious side effects, its clinical use is considerably limited. AIMS: This study was mapped to investigate the potential effects of desloratadine (DES) against CIS-induced nephrotoxicity and testicular injury. MAIN METHODS: DES (5 and 10 mg/kg) was orally administered for 10 days, and CIS was injected once (10 mg/kg, i.p.) in adult male rats on day 9 to induce both renal and testicular toxicity. KEY FINDINGS: DES significantly attenuated CIS-induced alterations in histopathology and biomarkers. DES resulted in a significant reduction in serum levels of creatinine (Cr), urea, and blood urea nitrogen (BUN), in addition to a marked decrease in urinary levels of albumin and total protein. Additionally, DES efficiently reinstated the oxidative balance by preventing the elevation of malondialdehyde (MDA) and enhancing superoxide dismutase (SOD) activity, and increasing glutathione (GSH) levels. Moreover, DES produced a profound decrease in renal and testicular levels of nucleotide-binding domain-(NOD) like receptor 3 (NLRP3), interleukin (IL)-1ß, and caspase-1 when compared to the CIS group. Furthermore, DES significantly decreased CIS-induced elevation in toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB) levels in both renal and testicular tissues. SIGNIFICANCE: DES can be used as adjuvant therapy with CIS in cancerous cases, pending further clinical studies.