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Kinin B2 receptor does not exert renoprotective effects on mice with glycerol-induced rhabdomyolysis
Pedro Paulo Gattai, Fernando Francisco Pazello Mafra, Frederick Wasinski, Sandro Soares Almeida, Marcos Antônio Cenedeze, Denise Maria Avancini Costa Malheiros, Reury Frank Pereira Bacurau, Carlos Castilho Barros, Niels Olsen Saraiva Câmara, Ronaldo Carvalho Araujo
Pedro Paulo Gattai, Fernando Francisco Pazello Mafra, Frederick Wasinski, Ronaldo Carvalho Araujo, Department of Biophysics, Laboratory of Genetics and Exercise Metabolism, Federal University of Sao Paulo - UNIFESP, Sao Paulo, CEP 04039-032, Brazil
Sandro Soares Almeida, Niels Olsen Saraiva Câmara, Federal University of Sao Paulo - UNIFESP, Sao Paulo, CEP 04039-032, Brazil
Marcos Antônio Cenedeze, Nephrology Division, Laboratory of Clinical and Experimental Immunology, Federal University of Sao Paulo – UNIFESP, Sao Paulo, CEP 04039-032, Brazil
Denise Maria Avancini Costa Malheiros, Renal Division, Department of Clinical Medicine, Laboratory of Renal Pathophysiology (LIM-16), Sao Paulo University - USP, Sao Paulo, CEP 04039-032, Brazil
Reury Frank Pereira Bacurau, School of Arts, Sciences and Humanities, Sao Paulo University - USP, Sao Paulo, CEP 04039-032, Brazil
Carlos Castilho Barros, Nutrition Faculty, Federal University of Pelotas, Rio Grande do Sul, CEP 96010-610, Brazil
Niels Olsen Saraiva Câmara, Department of Immunology, Laboratory of Transplantation in Immunobiology, Sao Paulo University - USP, Sao Paulo, CEP 05508-000, Brazil
Author contributions: Gattai PP, Mafra FFP, Wasinski F and Cenedeze MA performed the majority of experiments; Almeida SS, Malheiros DMAC and Barros CC provided vital reagents and analytical tools and were also involved in experiments; Gattai PP, Bacurau RFP, Camara NOS and Araujo RC were involved in editing manuscript, designed the study and wrote manuscript.
Supported by The National Council of Scientific and Technological Development - CNPq, No. 135020/2011-5
Correspondence to: Ronaldo Carvalho Araujo, PhD, Assistant Professor, Department of Biophysics, Laboratory of Genetics and Exercise Metabolism, Federal University of Sao Paulo - UNIFESP, Rua Pedro de Toledo, 669, 9º andar, Vila Clementino, Sao Paulo, CEP 04039-032, Brazil. araujo.ronaldo@unifesp.br
Telephone: +55-11-55764859
Received: December 4, 2013
Revised: April 24, 2014
Accepted: May 14, 2014
Published online: August 6, 2014
AIM: To investigate a potential protective role of the kinin B2 receptor in a glycerol-induced rhabdomyolysis mouse model.
METHODS: We separated 28 C57Bl/6 male mice into 4 groups: untreated WT animals, untreated B2 knockout mice, glycerol-treated WT and glycerol-treated B2 knockout mice. Glycerol-treated animals received one intramuscular injections of glycerol solution (50% v/v, 7 mL/kg). After 48 h, urine and blood samples were collected to measure creatinine and urea levels. Additionally, kidney samples were extracted for histological evaluation, and the mRNA expression levels of kinin B1 and B2 receptors and inflammatory mediators were measured by real-time polymerase chain reaction.
RESULTS: Serum creatinine and urea levels showed differences between untreated wild-type and glycerol-treated wild-type mice (0.66 ± 0.04 vs 2.61 ± 0.53 mg/dL, P < 0.01; and 33.51 ± 2.08 vs 330.2 ± 77.7 mg/dL, P < 0.005), and between untreated B2 knockout mice and glycerol-treated knockout mice (0.56 ± 0.03 vs 2.23 ± 0.87 mg/dL, P < 0.05; and 42.49 ± 3.2 vs 327.2 ± 58.4 mg/dL, P < 0.01), but there was no difference between the glycerol-treated wild-type and glycerol-treated knockout mice. Glycerol was able to induce a striking increase in kinin B2 receptor expression (> 30 times, 31.34 ± 8.9) in kidney. Animals injected with glycerol had a higher degree of tubular injury than untreated animals. Wild-type and knockout mice treated with glycerol intramuscularly present kidney injury, with impairment in renal function. However, B2 knockout mice treated with glycerol did not show a different phenotype regarding kidney injury markers, when compared to the wild-type glycerol-treated group.
CONCLUSION: We conclude that the kinin B2 receptor does not have a protective role in renal injury.
Core tip: In this work we are showing that glycerol-treated animals experienced impairment in renal function. Furthermore, we worked with kinin B2 receptor knockout mice and our results suggest that kinin B2 receptor does not exert renoprotective effects in this rhabdomyolysis model. In addition, we are presenting results of kidney expressions and we investigated several candidates that can participate in the kidney injury induced by glycerol.
