Venlafaxine mitigates cisplatin-induced nephrotoxicity via down-regulating apoptotic pathway in rats

• Published in: Chemico-biological interactions 2018-06, Vol.290, p.110-118
• Main Authors: El-Kashef, Dalia H., Sharawy, Maha H.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - toxicity; Antioxidants - metabolism; Apoptosis - drug effects; bcl-2-Associated X Protein - metabolism; Bcl-2/Bax; Caspase 3 - metabolism; Caspase-3; Catalase - metabolism; Cisplatin; Cisplatin - toxicity; Creatinine - blood; Down-Regulation - drug effects; Glutathione - metabolism; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Male; Nephrotoxicity; NF-kappa B - metabolism; Oxidative Stress - drug effects; p53; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Sprague-Dawley; Superoxide Dismutase - metabolism; Tumor Suppressor Protein p53 - metabolism; Venlafaxine; Venlafaxine Hydrochloride - pharmacology
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2018.05.015

The antidepressant venlafaxine, a norepinephrine and serotonin reuptake inhibitor, is recently identified for its anti-inflammatory role against many experimental models. In this study, the effect of venlafaxine against cisplatin-induced nephrotoxicity and bladder rings hypersensitivity towards acetylcholine were explored. Single injection of cisplatin (7 mg/kg, ip) in Sprague-Dawley rats instigated nephrotoxicity evidenced by hindering renal function (changes in kidney/body weight ratio, serum creatinine, BUN, albumin and urinary total protein levels which were supported by histopathology). In addition, cisplatin caused a profound oxidative stress, inflammation and apoptosis. Treatment with venlafaxine (50 mg/kg, po) managed to alleviate the nephrotoxicity indices and rehabilitate the antioxidant parameters (MDA, GSH, SOD and CAT) in addition to retaining NOx levels to the normal levels. Moreover, venlafaxine caused a decline in LDH and NF-κB levels supporting its anti-inflammatory effect. Additionally, the antiapoptotic effect was demonstrated by increasing Bcl-2, suppressing p53 and Bax renal levels, decreasing caspase-3 expression and by flow cytometry (annexin V and PI) that showed an increase in viable cells and a decrease in early apoptotic and necrotic cells. Furthermore, venlafaxine ameliorated bladder rings hyperreactivity to acetylcholine and improved histopathologic findings. In brief, venlafaxine ameliorated nephrotoxicity and bladder rings hyperreactivity caused by cisplatin through acting as an antioxidant, anti-inflammatory and antiapoptotic agent. •Venlafaxine attenuated cisplatin-induced nephrotoxicity in rats.•Venlafaxine alleviated oxidative stress associating nephrotoxicity.•Venlafaxine possesses anti-inflammatory and antiapoptotic effects.•Venlafaxine ameliorated bladder rings responsiveness to acetylcholine.