Carnosic acid attenuates renal injury in an experimental model of rat cisplatin-induced nephrotoxicity.

Nephrotoxicity is one of the serious dose limiting side effects of cisplatin when used in the treatment of various malignant conditions. Accumulating evidence suggests that oxidative stress caused by free radicals and apoptosis of renal cells contributes to the pathogenesis of cisplatin-induced nephrotoxicity. Present study was aimed to explore the effect of carnosic acid, a potent antioxidant, against cisplatin induced oxidative stress and nephrotoxicity in rats. A single dose of cisplatin (7.5mg/kg) caused marked renal damage, characterized by a significant (P<0.05) increase in serum creatinine, blood urea nitrogen (BUN) and relative weight of kidney with higher kidney MDA (malondialdehyde), tROS (total reactive oxygen species), caspase 3, GSH (reduced glutathione) levels and lowered tissue nitrite, SOD (superoxide dismutase), CAT (catalase), GSH-Px (glutathione peroxidase), GR (glutathione reductase) and GST (glutathione S-transferase) levels compared to normal control. Carnosic acid treatment significantly (P<0.05) attenuated the increase in lipid peroxidation, caspase-3 and ROS generation and enhanced the levels of reduced glutathione, tissue nitrite level and activities of SOD, CAT, GSH-Px, GR and GST compared to cisplatin control. The present study demonstrates that carnosic acid has a protective effect on cisplatin induced experimental nephrotoxicity and is attributed to its potent antioxidant and antiapoptotic properties.

Sahu BD ，Rentam KK ，Putcha UK ，Kuncha M ，Vegi GM ，Sistla R ... -  《-》

Hesperidin attenuates cisplatin-induced acute renal injury by decreasing oxidative stress, inflammation and DNA damage.

Nephrotoxicity is an important complication in cancer patients undergoing cisplatin therapy. Oxidative stress, inflammation and apoptosis/necrosis are the major patho-mechanisms of cisplatin induced nephrotoxicity. In the present study, hesperidin, a naturally-occurring bioflavonoid has been demonstrated to have protective effect on cisplatin-induced renal injury in rats. Cisplatin intoxication resulted in structural and functional renal impairment which was revealed by massive histopathological changes and elevated blood urea nitrogen and serum creatinine levels, respectively. Renal injury was associated with oxidative stress/lipid peroxidation as evident by increased reactive oxygen species (ROS) and malondialdehyde (MDA) formation with decreased levels of antioxidants such as reduced glutathione, vitamin C, catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase and glutathione-S-transferase. Cisplatin administration also triggered inflammatory response in rat kidneys by inducing pro-inflammatory cytokine, TNF-α, with the increased expression of myeloperoxidase (MPO). Furthermore, cisplatin increased the activity of caspase-3 and DNA damage with decreased tissue nitric oxide levels. Hesperidin treatment significantly attenuated the cisplatin-induced oxidative stress/lipid peroxidation, inflammation (infiltration of leukocytes and pro-inflammatory cytokine), apoptosis/necrosis (caspase-3 activity with DNA damage) as well as increased expression of nitric oxide in the kidney and improved renal function. Thus, our results suggest that hesperidin co-administration may serve as a novel and promising preventive strategy against cisplatin-induced nephrotoxicity.

Sahu BD ，Kuncha M ，Sindhura GJ ，Sistla R ... -  《-》

Effects of different doses of hyperbaric oxygen on cisplatin-induced nephrotoxicity.

Aydinoz S ，Uzun G ，Cermik H ，Atasoyu EM ，Yildiz S ，Karagoz B ，Evrenkaya R ... -  《RENAL FAILURE》

Protective effects of increasing vitamin E and a doses on cisplatin-induced oxidative damage to kidney tissue in rats.

Dillioglugil MO ，Maral Kir H ，Gulkac MD ，Ozon Kanli A ，Ozdogan HK ，Acar O ，Dillioglugil O ... -  《UROLOGIA INTERNATIONALIS》

Role of ellagic acid against cisplatin-induced nephrotoxicity and oxidative stress in rats.

Ateşşahín A ，Ceríbaşi AO ，Yuce A ，Bulmus O ，Cikim G ... -  《BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY》