İlter İlhan1, Halil Aşçi2, Nursel Hasseyid2, Hatice Kubra Doğan3, Şerife Ağirca4, Melike Altintaş4, Muhammet Yusuf Tepebasi5. 1. Department of Biochemistry, Faculty of Medicine, Suleyman Demirel University, 32000, Isparta, Turkey. ilterilhan@sdu.edu.tr. 2. Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey. 3. Department of Bioengineering, Institute of Science, Suleyman Demirel University, Isparta, Turkey. 4. Department of Pathology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur, Turkey. 5. Department of Medical Genetic, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.
Abstract
BACKGROUND: Cisplatin (CPN) is used in the treatment of various cancers. However, the especially nephrotoxic effect is limiting its use. We aimed to evaluate the renoprotective effects of Irbesartan (IBN) on CPN-induced acute kidney injury via mitochondrial stress related apoptosis. METHODS AND RESULTS: 32 rats were divided into 4 groups as control, CPN, CPN + IBN and IBN. Water or IBN 50 mg/kg (orally) was administered for 7 days and a single dose of CPN (5 mg/kg) intraperitoneally was given CPN and CPN + IBN groups on fourth day of experiment. At the end of the experiment, serum BUN and creatinine (Cre) levels, which are the indicators of kidney function are measured. Bcl-2-associated X protein (Bax) and B-cell-lymphoma-2 (Bcl-2) mRNA levels were analyzed by using qRT-PCR from kidneys as a mitochondrial stress indicator. Also, active caspase-3(cas-3) protein and tumor necrosis factor alpha (TNF-α) expressions were examined by immunostaining of the kidney tissues. For evaluation of oxidative stress, malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) levels of renal tissues were measured and oxidative stress index (OSI) were calculated. CPN increased serum BUN and creatinine levels. Also, MDA, TOS and OSI levels were significantly elevated and TAS levels decreased in the CPN group. Moreover, CPN elevated the levels of Bax, active cas-3 protein and TNF-α expressions and suppressed Bcl-2 levels. IBN treatment reversed all these changes. CONCLUSIONS: IBN significantly regressed kidney damage by its anti-inflammatory and antioxidant activity via inhibiting mitochondrial stress. IBN could be used as a renoprotective agent in CPN-induced kidney injury.
BACKGROUND: Cisplatin (CPN) is used in the treatment of various cancers. However, the especially nephrotoxic effect is limiting its use. We aimed to evaluate the renoprotective effects of Irbesartan (IBN) on CPN-induced acute kidney injury via mitochondrial stress related apoptosis. METHODS AND RESULTS: 32 rats were divided into 4 groups as control, CPN, CPN + IBN and IBN. Water or IBN 50 mg/kg (orally) was administered for 7 days and a single dose of CPN (5 mg/kg) intraperitoneally was given CPN and CPN + IBN groups on fourth day of experiment. At the end of the experiment, serum BUN and creatinine (Cre) levels, which are the indicators of kidney function are measured. Bcl-2-associated X protein (Bax) and B-cell-lymphoma-2 (Bcl-2) mRNA levels were analyzed by using qRT-PCR from kidneys as a mitochondrial stress indicator. Also, active caspase-3(cas-3) protein and tumor necrosis factor alpha (TNF-α) expressions were examined by immunostaining of the kidney tissues. For evaluation of oxidative stress, malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) levels of renal tissues were measured and oxidative stress index (OSI) were calculated. CPN increased serum BUN and creatinine levels. Also, MDA, TOS and OSI levels were significantly elevated and TAS levels decreased in the CPN group. Moreover, CPN elevated the levels of Bax, active cas-3 protein and TNF-α expressions and suppressed Bcl-2 levels. IBN treatment reversed all these changes. CONCLUSIONS: IBN significantly regressed kidney damage by its anti-inflammatory and antioxidant activity via inhibiting mitochondrial stress. IBN could be used as a renoprotective agent in CPN-induced kidney injury.
Authors: Zsuzsanna K Zsengellér; Lena Ellezian; Dan Brown; Béla Horváth; Partha Mukhopadhyay; Balaraman Kalyanaraman; Samir M Parikh; S Ananth Karumanchi; Isaac E Stillman; Pál Pacher Journal: J Histochem Cytochem Date: 2012-04-17 Impact factor: 2.479
Authors: Partha Mukhopadhyay; Béla Horváth; Zsuzsanna Zsengellér; Jacek Zielonka; Galin Tanchian; Eileen Holovac; Malek Kechrid; Vivek Patel; Isaac E Stillman; Samir M Parikh; Joy Joseph; Balaraman Kalyanaraman; Pál Pacher Journal: Free Radic Biol Med Date: 2011-11-10 Impact factor: 7.376