Amelioration of cisplatin-induced nephrotoxicity by statins. 2013

Rajesh A Maheshwari, and Girish U Sailor, and Lalji Patel, and R Balaraman
Department of Pharmacy, Sumandeep Vidyapeeth, Piparia, Vadodara, Gujarat, India.

OBJECTIVE This study aimed to investigate the protective effect of simvastatin (SIM) and rosuvastatin (RST) on cisplatin (CIS)-induced nephrotoxicity. METHODS Adult female Wistar rats were divided into six groups: control group (Group 1) received 0.5% sodium carboxy methyl cellulose, group 2 and group 3 received SIM and RST for 10 days, respectively, and group 4 was injected single dose of CIS (7 mg/kg, i.p.). Group 5 and 6 were treated with SIM (10 mg/kg, p.o.) and RST (10 mg/kg, p.o.) for 10 days, respectively. All groups received cisplatin on the 5(th) day of treatment. Renal function tests like serum creatinine, urea, BUN, albumin, calcium, uric acid and magnesium, serum lipids, and markers of oxidative stress such as renal malondialdehyde (MDA) level and superoxide dismutase (SOD) and catalase (CAT) activities were measured. All tissues were investigated for histopathological changes. RESULTS CIS reduced the renal function, which was reflected with significant increase in serum urea, BUN, serum creatinine, uric acid and also significant decrease serum calcium, magnesium, albumin levels. In addition, cisplatin caused renal tubular damage with a higher MDA level, depletion of SOD and CAT activity, and elevation of serum lipids. SIM or RST ameliorate CIS induced renal damage due to improvement in renal function, oxidative stress, suppression of serum lipids, and histological alteration. CONCLUSIONS This finding suggests that simvastatin and rosuvastatin may have a protective effect against cisplatin-induced kidney damage via amelioration of lipid peroxidation as well as due to improvement of renal function, and lipid-lowering effects.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D007674 Kidney Diseases Pathological processes of the KIDNEY or its component tissues. Disease, Kidney,Diseases, Kidney,Kidney Disease
D008274 Magnesium A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
D008315 Malondialdehyde The dialdehyde of malonic acid. Malonaldehyde,Propanedial,Malonylaldehyde,Malonyldialdehyde,Sodium Malondialdehyde,Malondialdehyde, Sodium
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D001806 Blood Urea Nitrogen The urea concentration of the blood stated in terms of nitrogen content. Serum (plasma) urea nitrogen is approximately 12% higher than blood urea nitrogen concentration because of the greater protein content of red blood cells. Increases in blood or serum urea nitrogen are referred to as azotemia and may have prerenal, renal, or postrenal causes. (From Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984) BUN,Nitrogen, Blood Urea,Urea Nitrogen, Blood
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002374 Catalase An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA. Catalase A,Catalase T,Manganese Catalase,Mn Catalase
D002784 Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Epicholesterol
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum

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