OncoDrugs 2013 Vol.

1 (1), 10e-12e

Protective Agents for Chemotherapeutic Drugs Induced -Renal Failure

Protective Agents for Chemotherapeutic Drugs Induced -Renal Failure

Editorial AUTHOR: Sivakumar J T Gowder
AFFILIATION: Qassim University, College of Applied Medical Sciences, Buraidah, Kingdom of Saudi Arabia.

CORRESPONDING AUTHOR: via Sivakumar J T Gowder, Qassim University, College of Applied Medical Sciences, P.Box-6800, Buraidah 51452, Kingdom of Saudi Arabia; Tel: +966566873969; Fax: +96663802268; Email: sivakumargowder@yahoo.com

THE KIDNEYS are paired organs located on either side of the vertebral column. They are bean shaped and reddish-brown in color. The fist-sized organs are covered with a tough capsule of fibrous connective tissue, called a renal capsule. The concave side of a kidney has a depression where a renal artery enters and a renal vein and a ureter exit the kidney. The superior border of the right kidney is adjacent to the liver; and the spleen, for the left kidney. Therefore, both move down on inhalation. The renal artery transports blood to be filtered to the kidneys, and the renal vein carries filtered blood away from the kidneys (Mader and Windelspecht, 2012). The kidney is an organ of excretion, transport and metabolism. It is a complicated organ, comprising various cell types and having a neatly designed three dimensional organization (Yokoo et al., 2005). Due to structural complexity, the intact kidney is difficult to employ for adequate study of many biochemical, pharmacological and physiological processes. Primary cultures of proximal tubule cells have been considered as an appropriate model for the study of proximal tubule cell function or renal intact function (Gowder and McMartin, 2010). Kidney damage has been considered as a major public health hazard (Eckardt et al., 2013). Lifestyle diseases like diabetes and hypertension; and infectious conditions - cholera, malaria, schistosomiasis and hepatitis B are the important causes of renal failure (Broeck and De Wolf, 2012; WHO, 2002). Drugs, toxins, smoking, obesity, red meats, sodium, and sugar-sweetened beverages and food additives also cause renal failure (CDC, 2010; Chang et al., 2013; Menezes, 2013). Drug-induced renal dysfunction is more common in clinical practice in the world. Nearly 20% of patients in hospitals, in general, suffer from drug induced renal dysfunction (Kaufman et al., 1991; Nash et al., 2002; Bellomo, 2006). In the recent years, there has been an increase in the number of patients for diabetes, hypertension, cardiovascular diseases and cancer. Not only these prominent diseases but also the medications that have been used to treat these diseases have many adverse effects and finally cause renal

failure (Hoste and Kellum 2005). Large blood flow, presence of drug metabolizing enzymes and transporters are the important factors for the sensitivity of the kidney. Chemotherapeutic drugs cause renal diseases at different levels, and their effect range from an elevation in the level of serum creatinine to renal failure. Normally, the activity of drugs depends on the host / individual physiological system, the mode of renal handling of drugs and also pharmacological activity of the drugs. The chemotherapeutic drugs that have been studied thoroughly for renal disorders include-cisplatin, gemcitabine, anti-VEGF antibodies, bisphosphonates, methotrexate, ifosfamide, azacitidine, diaziquone, vincristine and cyclophosphamide, cetuximab, nitrosourea and chlorozotocin (LaunayVacher and Deray, 2006; Perazella and Mockel, 2011). There are certain protective agents that act against the chemotherapeutic drugs- induced nephrotoxicity. A survey on recent research (through the Pubmed search for the year 2013) showed several new findings on the activity of protective agents. Atorvastatin, a cholesterol lowering drug protects the nephrotoxic effect of doxorubicin through antioxidant and anti-apoptotic mechanisms (El-Moselhy and El-Sheikh, 2013). Chrysin (a naturally occurring flavanoid) also protects doxorubicin induced nephrotoxicity (Rashid et al., 2013). Taxol and dichloroacetic acids (DCA) are potential nephrotoxicants, and the toxicity of these drugs is mediated through Ser36-phosphorylated p66shc adaptor protein (p66shc). Manipulation of the expression of p66shc may provide protective measures for the nephrotoxicity of these drugs (Arany et al., 2013). Cisplatin, a known cytostatic drug, exhibits nephrotoxic effect. Though there are many transporters present in the plasma membrane to transport cisplatin, organic cation transporter-2 (OCT2) is found to be interesting since it is present in kidney and certain restricted tissues (cochlear and nervous cells). Inhibition of OCT2 will lead to decrease in cisplatin uptake and hence it is a target for a suitable protective therapy (Wensing and Ciarimboli, 2013).

Open Acess ISSN:

www.oncodrugs.org/journal

Novel orally active epoxyeicosatrienoic acid (EET) analogs inhibit cisplatin induced nephrotoxicity by reducing oxidative stress (Khan et al., 2013). Studies show the protective effect of Thespesia populnea, a flowering plant (Mika and Guruvayoorappan, 2013), D-ribose (Ueki et al., 2013), and cepharanthin, a biscoclaurin alkaloid, (Sogawa et al., 2013) on the cisplatin induced nephrotoxicity. Cinnamaldehyde, a widely used food flavor, has a high potential for human consumption in the world. The occurrence of cinnamaldehyde is widely noticed in most of the food, medicinal and cosmetic products. Anticancer activity of cinnamaldehyde has been revealed by many authors (Kim et al., 2010; Ng and Wu, 2009; Ka et al., 2003; Koh et al., 1998). In our studies, cinnamaldehyde treated rats (73.5 mg/kg body weight / day) showed many histopathological changes of kidney accompanied by an increased activity of marker enzymes and an imbalance in the antioxidant status (Gowder and Devaraj, 2006; Gowder and Devaraj, 2008). We have concluded that cinnamaldehyde in-

duced renal damage, is due to the reactive oxygen species that formed while in the free radical scavenging reactions (Gowder and Devaraj, 2010). Thus, the nephrotoxic drugs may induce oxidative stress and thereby result in renal damage or failure. Antioxidants (vitamins) play a significant role to ameliorate toxicity. Thus, fruits and vegetables in diet might protect human health from toxic effects of drugs at certain extent (Gowder 2013). While in chemotherapy, if the patients are given food rich in vitamin (vegetables and fruits etc), nephrotoxicity of the chemotherapeutic drugs can be prevented. Conflict of Interests The author declares no conflict of interests.
Received: 12/20/2013 Accepted: 12/22/2013 Published: 12/26/2013

REFERENCES Arany I, Clark JS, Reed D, Szab I, Ember I, Juncos LA (2013). The role of p66shc in taxol- and dichloroacetic acid-dependent renal toxicity. Anticancer Res 33(8), 3119-3122. Bellomo R (2006). The epidemiology of acute renal failure: 1975 versus 2005. Curr Opin Crit Care 12(6), 557-560. Broeck DV, De Wolf MJS (2012). Brefeldin A and Exo1 Completely Releave the Block of Cholera Toxin Action by a Dipeptide Metalloendoprotease Substrate. In: Cholera. Dr. Sivakumar Gowder (Ed.), InTech (Pub). ISBN: 978-953-51-0415-5. CDC (2010). National Chronic Kidney Disease Fact Sheet: General Information and National Estimates on Chronic Kidney Disease in the United States, 2010. U.S. Department of Health and Human Services (Pub). Atlanta, GA. Chang A, Van Horn L, Jacobs DR Jr, Liu K, Muntner P, et al. (2013). Lifestyle-related factors, obesity, and incident microalbuminuria: the CARDIA (Coronary Artery Risk Development in Young Adults) study. Am J Kidney Dis 62(2), 267-275. Eckardt KU, Coresh J, Devuyst O, Johnson RJ, Kttgen A, et al. (2013). Evolving importance of kidney disease: from subspecialty to global health burden. Lancet 382(9887), 158-169. El-Moselhy MA, El-Sheikh AA (2013). Protective mechanisms of atorvastatin against doxorubicin-induced hepato-renal toxicity. Biomed Pharmacother pii: S0753-3322(13)00107-8. Gowder SJT, McMartin KE (2010). Development of a primary culture system of rat kidney proximal tubule cells for transport and toxicity studies. Journal of Epithelial Biology and Pharmacology 3, 15-19. Gowder S JT, Devaraj H (2008). Food flavor cinnamaldehyde induced biochemical and histological changes in the kidney of male albino wistar rat. Environ Toxicol Pharmacol 26(1), 68-74. Gowder S JT, Devaraj H (2006). Effect of food flavor cinnamaldehyde on the antioxidant status of rat kidney. Basic Clin Pharmacol Toxicol 99(5), 379-382.

Gowder S, Devaraj H (2010). A review on the nephrotoxicity of food flavor cinnamaldehyde. Curr Bioact Compd 6(2), 106-117. Gowder S JT (2013). An updated review of toxicity of bisphenol A (BPA) with special reference to the kidney. Curr Mol Pharmacol (In Press). Hoste EA, Kellum JA (2006). Acute kidney injury: epidemiology and diagnostic criteria. Curr Opin Crit Care 12(6), 531-537. Ka H, Park HJ, Jung HJ, Choi JW, Cho KS, Ha J, et al. (2003). Cinnamaldehyde induces apoptosis by ROS-mediated mitochondrial permeability transition in human promyelocytic leukemia HL-60 cells. Cancer Lett 196(2), 143-152. Kaufman J, Dhakal M, Patel B, Hamburger R (1991). Community-acquired acute renal failure. Am J Kidney Dis 17(2), 191-198. Khan MA, Liu J, Kumar G, Skapek SX, Falck JR, Imig JD (2013). Novel orally active epoxyeicosatrienoic acid (EET) analogs attenuate cisplatin nephrotoxicity. FASEB J 27(8), 2946-2956. Kim BH, Lee YG, Lee J, Lee JY, Cho JY (2010). Regulatory effect of cinnamaldehyde on monocyte/macrophage-mediated inflammatory responses. Mediators Inflamm 2010, 529359. Koh WS, Yoon SY, Kwon BM, Jeong TC, Nam KS, Han MY (1998). Cinnamaldehyde inhibits lymphocyte proliferation and modulates T-cell differentiation. Int J Immunopharmacol 20(11), 643-660. Launay-Vacher V and Deray G (2006). Anticancer drugs and the kidney chronic renal insufficiency in cancer patients, dosage adjustment and renal toxicity of anticancer drugs. European kidney & urological disease, 1-5. Mader SS, Windelspecht M (2012). Urinary system. In : Human Biology, McGraw Hill Higher Education (Ed), New York. pages: 217-238. ISBN 0-07-352546-4. Menezes C, Valerio E, Dias E (2013). The Kidney Vero-E6 Cell Line: A Suitable Model to Study the Toxicity of Microcystins:. In: New Insights into Toxicity and Drug Testing. Dr. Sivakumar Gowder (Ed.), InTech (Pub). ISBN: 978-953-51-0946-4.

Open Acess

www.oncodrugs.org/journal

Mika D, Guruvayoorappan C (2013). The effect of Thespesia populnea on cisplatin induced nephrotoxicity. J Cancer Res Ther 9(1), 50-3. Nash K, Hafeez A, Hou S (2002). Hospital-acquired renal insufficiency. Am J Kidney Dis 39(5), 930-936. Ng L, Wu S (2011). Antiproliferative activity of cinnamomum cassia constituents and effects of pifithrin-alpha on their apoptotic signaling pathways in hep g2 cells. Evid Based Complement Alternat Med 2011, 492148. Perazella MA, Moeckel GW (2010). Nephrotoxicity from chemotherapeutic drugs: clinical manifestations, pathobiology, and prevention/therapy. Semi Nephrol 30(6), 570-581. (Erratum in: Semi Nephrol 31(3), 317.) Rashid S, Ali N, Nafees S, Ahmad ST, Arjumand W, Hasan SK, Sultana S (2013). Alleviation of doxorubicin-induced nephrotoxicity and hepatotoxicity by chrysin in Wistar rats. Toxicol Mech Methods 23(5):337-45. Sogawa N, Hirai K, Sogawa C, Ohyama K, Miyazaki I, Tsukamoto G, Asanuma M, Sasaki A, Kitayama S (2013). Protective

effect of cepharanthin on cisplatin-induced renal toxicity through metallothionein expression. Life Sci 92(12), 727-732. Ueki M, Ueno M, Morishita J, Maekawa N (2013). D-ribose ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in mice. Tohoku J Exp Med 229(3):195-201. Wensing KU, Ciarimboli G (2013). Saving ears and kidneys from cisplatin. Anticancer Res 33(10), 4183-4188. WHO (2002). Reducing Risks, Promoting Healthy Life. In The World Health Report 2002, WHO (Geneva). ISBN 92 4 156207 2 Yokoo T, Ohashi T, Shen JS, Sakurai K, Miyazaki Y, et al. (2005). Human mesenchymal stem cells in rodent whole-embryo culture are reprogrammed to contribute to kidney tissues. Proc Nat Acad Sci USA 102(9), 3296-3300. .

This work is licensed under a Creative Commons Attribution NonCommercial 3.0 License (CC BYNC3.0). Copyright Sivakumar J T Gowder., 2013 Licensee PCR LLC, USA OncoDrugs 2013; Vol. 1(1). 10e-12e

Open Acess

www.oncodrugs.org/journal