DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20181162

Diclofenac-induced biochemical changes in nephrotoxicity among male Albino rats

Sivaraj R., Umarani S.

Abstract


Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with adverse renal effects caused by the reduction in synthesis of renal prostaglandins in sensitive persons or animal species, and potentially during long-term use in non-sensitive persons if resistance to side effects decreases with age. The effects of diclofenac sodium on the kidneys were studied during 4 1/2 hours in eight patients with normal renal function. Urinary output decreased within 10 min after the injection, and maximally by 80%. The renal plasma flow and the glomerular filtration rate initially diminished significantly, by 35%, but began to increase after only 2 hours. The dominant and persistent effect was a reduction of free water clearance, with maximum fall from 5.9 to 0.08ml/min after 2 1/2 hours. Aim: The aim of this study was to evaluate the effects of diclofenac-induced acute nephrotoxicity using biochemical parameters in rats.

Methods: 12 male Wistar rats allotted in 4 equal groups were intraperitoneally injected with 0, 10, 50 and 100mg/kg diclofenac, respectively and 12 hours after injection, blood serum samples were collected for assessment of basic renal function test parameters such as urea, creatinine, and uric acid, sodium, Potassium.

Results: Rats treated up to 50mg/kg diclofenac were considered to be within normal range in rats. By increase in dose more than 50mg/kg showed significant increases in uremia were evidenced in intoxicated animals. Observed specifically in group IV Rats.

Conclusions: In this study, uremia, as an indicator of kidney damage, was significantly increased depending on dose. Diclofenac may cause kidney damage depending on dose and this effect may also be observed. NSAIDs-induced nephrotoxicity may be due to the inhibitory effect of these drugs on prostaglandin synthesis, thus causing kidney ischemia.


Keywords


Diclofenac, Impaired renal function, Nephrotoxicity, Uremia

Full Text:

PDF

References


Arroyo V, Planas R, Gaya J, Deulofeu R, Rimola A, Pérez‐Ayuso Om, et al. Sympathetic nervous activity, renin‐angiotensin system and renal excretion of prostaglandin E2 in cirrhosis. Relationship to functional renal failure and sodium and water excretion. European journal of clinical investigation. 1983 Jun 1;13(3):271-8.

Bosch–Marcé M, Clària J, Titos E, Masferrer JL, Altuna R, Poo JL, et al. Selective inhibition of cyclooxygenase 2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites. Gastroenterology. 1999 May 1;116(5):1167-75.

Boyer TD, Zia P. Reynolds, T.B. Effect of indomethacin and prostaglandin A1 on renal function and plasma renin activity in alcoholic liver disease. Gastroenterology. 1979;77:215-22.

Brater DC. Effects of nonsteroidal anti-inflammatory drugs on renal function: focus on cyclooxygenase-2–selective inhibition. The American Journal of Medicine. 1999 Dec 13;107(6):65-70.

Campbell MS, Makar GA. Safety of short‐term administration of celecoxib in decompensated cirrhosis. Hepatology. 2005 Jul 1;42(1):237.

Cheng HF, Wang JL, Zhang MZ, Miyazaki Y, Ichikawa I, McKanna JA, et al. Angiotensin II attenuates renal cortical cyclooxygenase-2 expression. The Journal of clinical investigation. 1999 Apr 1;103(7):953-61.

Clària, J. Safety of short-term administration of celecoxib in decompensated cirrhosis. Hepatology 2005;42:238.

Ginès P, Schrier RW. Renal failure in cirrhosis. New England Journal of Medicine. 2009 Sep 24;361(13):1279-90.

Guevara M, Abecasis R, Terg R. Effect of celecoxib on renal function in cirrhotic patients with ascites. A pilot study. Scandinavian J of Gastroenterology. 2004 Jan 1;39(4):385-6.

Harding P, Sigmon DH, Alfie ME, Huang PL, Fishman MC, Beierwaltes WH, et al. Cyclooxygenase-2 mediates increased renal renin content induced by low-sodium diet. Hypertension. 1997 Jan 1;29(1):297-302.

Ichihara A, Imig JD, Inscho EW, Navar LG. Cyclooxygenase-2 participates in tubular flow-dependent afferent arteriolar tone: interaction with neuronal NOS. American Journal of Physiology-Renal Physiology. 1998 Oct 1;275(4):F605-12.

Kammerl MC, Nüsing RM, Schweda F, Endemann D, Stubanus M, Kees F, et al. Low sodium and furosemide‐induced stimulation of the renin system in man is mediated by cyclooxygenase 2. Clinical Pharmacology & Therapeutics. 2001 Nov 1;70(5):468-74.

Komhoff MA, Grone HJ, Klein TH, Seyberth HW, Nusing RM. Localization of cyclooxygenase-1 and-2 in adult and fetal human kidney: implication for renal function. American Journal of Physiology-Renal Physiology. 1997 Apr 1;272(4):F460-8.

Bosch–Marcé M, Clària J, Titos E, Masferrer JL, Altuna R, Poo JL, et al. Selective inhibition of cyclooxygenase 2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites. Gastroenterology. 1999 May 1;116(5):1167-75.

LeLorier J, Bombardier C, Burgess E, Moist L, Wright N, Cartier P, et al. Practical considerations for the use of nonsteroidal anti-inflammatory drugs and cyclo-oxygenase-2 inhibitors in hypertension and kidney disease. The Canadian Journal of Cardiology. 2002 Dec;18(12):1301-8.

López‐Parra M, Clària J, Planagumà A, Titos E, Masferrer JL, Woerner BM, et al. Cyclooxygenase‐1 derived prostaglandins are involved in the maintenance of renal function in rats with cirrhosis and ascites. British journal of pharmacology. 2002 Feb 1;135(4):891-900.

Noroian G, Clive D. Cyclo-oxygenase-2 inhibitors and the kidney. Drug safety. 2002 Mar 1;25(3):165-72.

Ros J, Claria J, Jimenez W, Bosch‐Marcé M, Angeli P, Arroyo V, et al. Role of nitric oxide and prostacyclin in the control of renal perfusion in experimental cirrhosis. Hepatology. 1995 Sep 1;22(3):915-20.

Schricker KA, Hamann MA, Kurtz AR. Nitric oxide and prostaglandins are involved in the macula densa control of the renin system. American Journal of Physiology-Renal Physiology. 1995 Dec 1;269(6):F825-30.

Turull À, Piera C, Queralt J. Acute effects of the anti-inflammatory cyclooxygenase-2 selective inhibitor, flosulide, on renal plasma flow and glomerular filtration rate in rats. Inflammation. 2001 Apr 1;25(2):119-28.