Abstract
Cisplatin has been frequently used for treatment of wide variety of tumors. The use of cisplatin is associated with severe cytotoxicity such as nephrotoxicity, hepatotoxicity and spermiotoxicity which radically limits its clinical use. The present study aimed to investigate the possible protective effects of multiple doses of hesperidin against cisplatin-induced nephrotoxicity induced by single i.p injection of cisplatin (7.5 mg/kg). Hesperidin was given to rats at two different doses (100 and 200 mg/kg p.o) for 7 days starting one day before cisplatin injection. Blood samples were collected for determination of serum creatinine and Blood Urea Nitrogen (BUN) levels. Kidneys were used for the determination of Malondialdehyde (MDA), Glutathione (GSH) and total nitrate and nitrite contents. Liver samples were also used for histopathological examination. Results showed that hesperidin significantly reduced cisplatin-induced elevations in serum creatinine and BUN levels. It also significantly reduced kidney MDA and NO content and elevated GSH content. In conclusion, hesperidin greatly protected kidney against cisplatin-induced toxicity in a dose-dependent manner.
Highlights
Cisplatin has been frequently considered as the first choice chemotherapeutic agent for treatment of a wide variety of solid tumors, including ovarian, testicular, bladder, head and neck, esophageal and small cell lung cancers (Weijl et al, 1997; Previati et al, 2006; Shona et al, 2012)
Knowing that cisplatin chemotherapy induces a fall in plasma antioxidant levels, which may reflect a failure of the antioxidant defense mechanism against the oxidative damage induced (Weijl et al.,1998), the aim of the present study is that combination treatment of cisplatin and a naturally occurring antioxidant flavonoid hesperidin may be a useful strategy to protect against cisplatin-induced nephrotoxicity
Effect of hesperidin on cisplatin-induced elevations in serum Cr and Blood Urea Nitrogen (BUN) levels: Cisplatin significantly increased serum Cr and BUN levels when compared to normal control group
Summary
Cisplatin (cis-diammine-dichloro-platinum) has been frequently considered as the first choice chemotherapeutic agent for treatment of a wide variety of solid tumors, including ovarian, testicular, bladder, head and neck, esophageal and small cell lung cancers (Weijl et al, 1997; Previati et al, 2006; Shona et al, 2012). About 70-80% of patients respond to platinum treatment Such an initial effect is not robust and results in a 5-year patient survival of only 15-20%, as tumors become resistant to therapy (Siddik, 2003). The dose scale necessary to overcome even a small increase in cellular resistance can lead to severe cytotoxicity in normal cells such as nephrotoxicity, hepatotoxicity and spermiotoxicity (Zicca et al, 2002; Atessahin et al, 2006; Palipoch et al, 2014) which radically limits the clinical usefulness of cisplatin-based therapy. The mechanism of cisplatin-induced nephrotoxicity has been clearly reported through multiple mechanisms including hypoxia, the generation of free radicals, inflammation and apoptosis with an increase in the proapoptotic protein Bax and a decrease in the antiapoptotic protein Bcl-2(Tsuruya et al, 2003)
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