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Metabolomic study of cisplatin-induced nephrotoxicity
D. Portilla, S. Li, K.K. Nagothu, J. Megyesi, B. Kaissling, L. Schnackenberg, R.L. Safirstein, R.D. Beger Kidney International Volume 69, Issue 12, Pages (June 2006) DOI: /sj.ki Copyright © 2006 International Society of Nephrology Terms and Conditions
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Figure 1 Effect of fibrate WY (WY) on renal function in mice after single dose of cisplatin. Mice were fed with either a regular diet or a diet containing 0.1% WY for 7 days before cisplatin administration, as described in Materials and Methods. BUN and creatinine levels were measured at day 1, 2, and 3 after saline (control)-, cisplatin-, or cisplatin+WY-treated mice. Bars correspond to means±s.e. of at least six independent experiments under each condition. (a) and (b) Changes in BUN and creatinine levels, respectively, after saline or cisplatin administration in PPARα wild-type mice. *P<0.005 when animals were compared with control by unpaired Student's t-test. Kidney International , DOI: ( /sj.ki ) Copyright © 2006 International Society of Nephrology Terms and Conditions
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Figure 2 Electron microscopy of mouse kidney. Representative electron micrographs of the deep cortex from kidneys of (a) control, (b) cisplatin, and (c) fibrate+cisplatin-treated mice. S3: proximal tubules; T: thick ascending limbs, CD: collecting duct. Bar ∼50 μm. Kidney International , DOI: ( /sj.ki ) Copyright © 2006 International Society of Nephrology Terms and Conditions
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Figure 3 Effect of fibrate (WY) and cisplatin on neutral lipid accumulation. Mouse kidney frozen sections were obtained from animals subjected to four experimental conditions, processed, and stained with oil red O dye as described in Materials and Methods. Depicted are the pictures obtained from oil red O staining of kidney sections from (a) control, (b) WY-treated, (c) cisplatin, and (d) WY+ciplatin-treated mice. Kidney International , DOI: ( /sj.ki ) Copyright © 2006 International Society of Nephrology Terms and Conditions
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Figure 4 Representative 1D 1H NMR spectra of C) control (C) and following administration of cisplatin (D1) 24 h, (D2) 48 h postdosing, and (D3) 72 h postdosing. Kidney International , DOI: ( /sj.ki ) Copyright © 2006 International Society of Nephrology Terms and Conditions
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Figure 5 Principal component (PC) scores plot showing the changes from control over a 72 h period following administration of cisplatin. Kidney International , DOI: ( /sj.ki ) Copyright © 2006 International Society of Nephrology Terms and Conditions
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Figure 6 3D Principal component (PC) scores plot indicating the effects of the PPARα ligand (WY) on cisplatin-induced ARF. Kidney International , DOI: ( /sj.ki ) Copyright © 2006 International Society of Nephrology Terms and Conditions
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Figure 7 Effect of cisplatin on NEFA levels in serum, urine, and kidney tissue. Mice were administered saline (control) or cisplatin (20 mg/kg BW) by a single intraperitoneal injection. (a) NEFA levels were measured at days 1, 2, and 3 after cisplatin injection in serum, urine, and kidney tissue homogenates as described in Materials and Methods. Bars correspond to means±s.e. of at least six independent experiments under each condition. *P<0.05, compared with control by unpaired Student's t-test. (b) Effect of cisplatin and fibrate (WY) on NEFA levels. Wild-type mice were fed with either a regular or WY-containing diet and then were given saline (control and WY groups) or cisplatin (cisplatin and cisplatin+WY groups). NEFA levels were measured at day 3 after cisplatin injection in serum, urine, and kidney tissue homogenates as described in Materials and Methods Results are expressed as the means±s.e. †P<0.05 compared to cisplatin; *P<0.05 compared with control by unpaired Student's t-test. Kidney International , DOI: ( /sj.ki ) Copyright © 2006 International Society of Nephrology Terms and Conditions
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Figure 8 Effect of cisplatin on TG levels in serum, urine, and kidney tissue. Mice were administered saline (control) or cisplatin (20 mg/kg BW) by a single intraperitoneal injection. (a) TG levels were measured in serum, urine, and kidney tissues at days 1, 2, and 3 after cisplatin injection as described in Materials and Methods. Bars correspond to means±s.e. of at least six independent experiments under each condition. **P<0.005 compared with control by unpaired Student's t-test. (b) Effect of cisplatin and fibrate (WY) on TG levels. Wild-type mice were fed with either a regular diet or WY-containing diet and then were given saline (control and WY groups) or cisplatin (cisplatin and cisplatin+WY groups). TG levels were measured in the serum, and kidney tissue homogenates at day 3 after cisplatin injection as described in Materials and Methods. Results are expressed as the means±s.e. †P<0.05 compared to cisplatin; *P<0.05, **P<0.005 compared with control by unpaired Student's t-test. Kidney International , DOI: ( /sj.ki ) Copyright © 2006 International Society of Nephrology Terms and Conditions
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Figure 9 Effect of cisplatin on glucose levels in serum, urine, and kidney tissue. Mice were administered saline (control) or cisplatin (20 mg/kg BW) by a single intraperitoneal injection. (a) Glucose levels were measured at days 1–3 after cisplatin injection in serum, urine, and kidney tissue homogenates as described in Materials and Methods. Bars correspond to means±s.e. of at least six independent experiments under each condition. *P<0.05, **P<0.005 compared with control by unpaired Student's t-test. (b) Effect of cisplatin and fibrate (WY) on glucose levels. Wild-type mice were fed with either a regular or WY-containing diet, and then were given saline (control and WY groups) or cisplatin (cisplatin and cisplatin+WY groups). Glucose levels were measured at day 3 after cisplatin injection in serum, urine, and kidney tissue homogenates as described in Materials and Methods Results are expressed as the means±s.e. †P<0.05 compared to cisplatin; *P<0.05, **P<0.005 compared with control by unpaired Student's t-test. Kidney International , DOI: ( /sj.ki ) Copyright © 2006 International Society of Nephrology Terms and Conditions
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