The Cannabinoid-2 receptor agonist, 1-phenylisatin, protects against cisplatin-induced nephrotoxicity in mice

Aim: The present study investigated the potential protective effect of a selective Cannabinoid-2 (CB2) receptor agonist, 1-phenylisatin, in acute nephrotoxicity induced by cisplatin.Materials and methods: Animals were arranged into 5 groups. Group I; normal saline, group II; 1-phenylisatin for 7 days, group III: received a single injection of cisplatin (20 mg/kg, i.p.) on day 5, group IV: 1-phenylisatin for 7 days and cisplatin on day 5 and group V: AM630, CB2 antagonist, 15 min before 1-phenylisatin for 7 days and a single injection of cisplatin on day 5. Mice were sacrificed 72 h after cisplatin injection. Kidneys were isolated for histopathological and biochemical analyses. Nephrotoxicity parameters including serum creatinine and urea were assessed as well as histopathological examination was done. Also, Oxidative stress markers; MDA and GSH, inflammatory markers; TNF-alpha, NF-Kappa B (p65), MCP-1, MIP-2, and ICAM-1, along with apoptotic markers, Bax, Bcl2, and caspase-3 were studied. Further, CB2 receptor expression was investigated.Key findings: Cisplatin injection increased serum creatinine and urea levels, and increased lipid peroxidation, decreased glutathione level and increased the renal expression of pro-inflammatory markers, TNF-alpha, NF-Kappa B, MCP-1, MIP-2, and ICAM-1, along with increased apoptotic markers and significantly reduced the expression of the anti-apoptotic Bcl2. Pretreatment with 1-phenylisatin significantly counteracted these effects. The CB2 re-ceptor antagonist; AM630, increased the renal expression of caspase-3 and Bax whereas Bcl2 expression decreased.Significance: 1-Phenylisatin protected against cisplatin-induced nephrotoxicity owing to its anti-apoptotic, anti-inflammatory, and antioxidant effects. These actions were mostly mediated through CB2 receptor.

Automated summary

This study aimed to investigate the potential protective effects of a selective CB2 receptor agonist, 1-phenylisatin, on acute nephrotoxicity induced by cisplatin. The results showed that 1-phenylisatin significantly mitigated the damage to the kidneys caused by cisplatin through its anti-apoptotic, anti-inflammatory, and antioxidant effects. These effects were mainly mediated through the CB2 receptor.