TAURINE ATTENUATES HYPERTENSION AND RENAL DYSFUNCTION INDUCED BY CYCLOSPORINE A IN RATS

• Published in: Clinical and experimental pharmacology & physiology Vol. 33; no. 3; pp. 189 - 196
• Main Authors: Hagar, Hanan H, El Etter, Eman, Arafa, Maha
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Science Pty 01-03-2006
• Subjects: Animals; Blood Pressure - drug effects; Body Weight - drug effects; catalase; Catalase - metabolism; Cyclosporine - antagonists & inhibitors; Cyclosporine - toxicity; cyclosporine A; glutathione; Glutathione - metabolism; glutathione peroxidase; Glutathione Peroxidase - metabolism; Heart Rate - drug effects; hypertension; Hypertension - drug therapy; Immunosuppressive Agents - antagonists & inhibitors; Immunosuppressive Agents - toxicity; Kidney - pathology; Kidney Diseases - chemically induced; Kidney Diseases - drug therapy; Kidney Diseases - pathology; Kidney Function Tests; Male; nephrotoxicity; nitric oxide; Nitric Oxide - blood; Rats; Rats, Wistar; superoxide dismutase; Superoxide Dismutase - metabolism; taurine; Taurine - therapeutic use; Thiobarbituric Acid Reactive Substances - metabolism; thiobarbituric acid-reactive substances
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/j.1440-1681.2006.04345.x

SUMMARY
1
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 β‐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.