Taurine attenuates hypertension and renal dysfunction induced by cyclosporine A in rats. 2006

Hanan H Hagar, and Eman El Etter, and Maha Arafa
Department of Pharmacology, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia. hananhhagar@yahoo.com

Cyclosporine A (CsA) is the first-line immunosuppressant used for the management of solid organ transplantation and autoimmune diseases. Nephrotoxicity is the major limitation of CsA use. Recent evidence suggests that reactive oxygen species (ROS) play an important role in mediating CsA-induced hypertension and nephrotoxicity. Taurine, the major intracellular free beta-amino acid, is known to be an endogenous anti-oxidant and membrane-stabilizing agent. The present study was designed to investigate the effects of taurine on CsA-induced oxidative stress, hypertension and renal dysfunction. 2. Animals were assigned into four groups of seven rats each as follows: (i) control group, receiving vehicle (olive oil; 1 mL/kg, s.c.); (ii) CsA group, given CsA (25 mg/kg per day, s.c.) for 21 days; (iii) taurine group, supplemented with taurine (1% in the drinking water); and (iv) taurine + CsA group, treated with taurine 3 days before and concurrently during CsA injections for 21 days. 3. Cyclosporine A administration elevated blood pressure, reduced serum nitric oxide (NO) levels and deteriorated renal function, as assessed by increased serum creatinine levels and proteinuria and reduced urine flow rate and creatinine clearance compared with vehicle-treated rats. Cyclosporine A induced oxidative stress, as indicated by increased renal tissue concentrations of thiobarbituric acid-reactive substances and reduced concentrations of renal glutathione, glutathione peroxidase and superoxide dismutase. Conversely, no change was noted in renal catalase activity. Moreover, the kidneys of CsA-treated rats showed interstitial inflammation and renal tubular atrophy. 4. Taurine markedly reduced elevated blood pressure, attenuated renal dysfunction and the reduction in serum NO levels and counteracted the deleterious effects of CsA on oxidative stress markers. Furthermore, taurine ameliorated CsA-induced morphological changes. 5. These data clearly indicate the protective potential of taurine against CsA-induced hypertension and nephrotoxicity and suggest a significant contribution of its anti-oxidant property to this beneficial effect.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
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
D007677 Kidney Function Tests Laboratory tests used to evaluate how well the kidneys are working through examination of blood and urine. Function Test, Kidney,Function Tests, Kidney,Kidney Function Test,Test, Kidney Function,Tests, Kidney Function
D008297 Male Males
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
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

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