Affiliation:
1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University , Cairo , Egypt
Abstract
Abstract
Context
Renal toxicity correlated with cisplatin administration curbs its clinical application. Accordingly, the identification of novel protective agents is important. Forskolin provides anti-inflammatory, anti-oxidant as well as anti-cancer effects.
Objectives
This study aimed to explore the nephroprotective effect of forskolin in a model of cisplatin-induced acute renal toxicity in rats in addition to exploring the possible mechanisms.
Methods
Rats were sorted into four groups: control group, cisplatin group, cisplatin/forskolin group that was given forskolin (10 mg/kg, i.p.) 1 week before cisplatin and forskolin-only group. Nephrotoxicity markers were tested in the blood. Tissues were used to assess histopathology, oxidative stress, inflammation and apoptosis.
Key findings
In cisplatin-injected rats, the nephrotoxicity indices were particularly increased. Cisplatin markedly reduced the levels of reduced glutathione and superoxide dismutase. Also, malondialdehyde and Nicotinamide adenine dinucleotide phosphate oxidase were increased. In addition, the pro-inflammatory cytokines and caspase-3 were elevated. Moreover, the epidermal growth factor expression was significantly reduced. Furthermore, marked histopathological changes were noted in the tissues of cisplatin-injected rats. Forskolin attenuated nephrotoxicity markers, inflammation, oxidative stress and apoptotic insults provoked via cisplatin. Moreover, cisplatin cytotoxic activity was not modulated by forskolin in human cultured cancerous cell lines.
Conclusion
Forskolin provides significant protection from cisplatin-evoked nephrotoxicity enhancing its therapeutic index.
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
Cited by
1 articles.
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