Naif O Al-Harbi1, Faisal Imam2, Mohammed M Al-Harbi1, Muzaffar Iqbal3, Ahmed Nadeem1, Othman A Al-Shahrah1, Hesham M Korashy1, Khalid A Al-Hosaini1, Mukhtar Ahmed4, Saleh Bahashwar5. 1. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Kingdom of Saudi Arabia. 2. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Kingdom of Saudi Arabia fimam@ksu.edu.sa. 3. Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Kingdom of Saudi Arabia. 4. Department of Zoology, College of Science, King Saud University, Kingdom of Saudi Arabia. 5. Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Kingdom of Saudi Arabia.
Abstract
INTRODUCTION: Tacrolimus is frequently used as immunosuppressive agent in organ transplantation but its clinical use is limited due to its marked nephrotoxicity. MATERIALS AND METHODS: Male Wistar albino rats weighing 150-200 g (10-12 weeks old) were used. Animals were divided into four groups. Group 1 served as control group and received normal saline, group 2 served as toxic group and received 2 mg/kg tacrolimus i.p., group 3 served as treatment group and received 2 mg/kg tacrolimus i.p. followed by 2 mg/kg aliskiren orally and group 4 served as drug per se group and received 2 mg/kg aliskiren orally. Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. RESULTS: Treatment with aliskiren decreased the tacrolimus-induced changes in biochemical markers of nephrotoxicity such as blood urea nitrogen and creatinine. Aliskiren also attenuated the effects of tacrolimus on oxidative stress parameters such as malondialdehyde, reduced glutathione and catalase. Histopathological and ultrastructural studies showed that aliskiren attenuated tacrolimus-induced renal damage. CONCLUSION: These results suggest that aliskiren has protective effects against tacrolimus-induced nephrotoxicity; implying that renin inhibitor may counteract nephrotic syndrome associated with immunosuppressant use.
INTRODUCTION:Tacrolimus is frequently used as immunosuppressive agent in organ transplantation but its clinical use is limited due to its marked nephrotoxicity. MATERIALS AND METHODS: Male Wistar albino rats weighing 150-200 g (10-12 weeks old) were used. Animals were divided into four groups. Group 1 served as control group and received normal saline, group 2 served as toxic group and received 2 mg/kg tacrolimus i.p., group 3 served as treatment group and received 2 mg/kg tacrolimus i.p. followed by 2 mg/kg aliskiren orally and group 4 served as drug per se group and received 2 mg/kg aliskiren orally. Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. RESULTS: Treatment with aliskiren decreased the tacrolimus-induced changes in biochemical markers of nephrotoxicity such as blood ureanitrogen and creatinine. Aliskiren also attenuated the effects of tacrolimus on oxidative stress parameters such as malondialdehyde, reduced glutathione and catalase. Histopathological and ultrastructural studies showed that aliskiren attenuated tacrolimus-induced renal damage. CONCLUSION: These results suggest that aliskiren has protective effects against tacrolimus-induced nephrotoxicity; implying that renin inhibitor may counteract nephrotic syndrome associated with immunosuppressant use.
Authors: Amal M Mahfoz; Hekma A Abd El-Latif; Lamiaa A Ahmed; Nahed M Hassanein; Afaf A Shoka Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2016-09-09 Impact factor: 3.000
Authors: Ágnes Prókai; Rózsa Csohány; Erna Sziksz; Domonkos Pap; Leonóra Balicza-Himer; Szilvia Boros; Balázs Magda; Ádám Vannay; Katalin Kis-Petik; Andrea Fekete; János Peti-Peterdi; Attila J Szabó Journal: Transplantation Date: 2016-02 Impact factor: 4.939