TY - JOUR
T1 - Potentiation of cisplatin-induced nephrotoxicity by repeated exposure to diesel exhaust particles
T2 - An experimental study in rats
AU - Nemmar, Abderrahim
AU - Beegam, Sumaya
AU - Yuvaraju, Priya
AU - Yasin, Javed
AU - Fahim, Mohamed A.
AU - Kazzam, Elsadig E.
AU - Alhaddabi, Ibrahim
AU - Ali, Badreldin H.
N1 - Funding Information:
This work was supported by a UAEU-SQU joint grant provided to both Prof. A. Nemmar (UAEU) and Prof. B.H. Ali (SQU), and by a research grant of the College of Medicine and Health Sciences, United Arab Emirates University.
Publisher Copyright:
© 2014 by the Society for Experimental Biology and Medicine.
PY - 2014/8/1
Y1 - 2014/8/1
N2 - Several epidemiological and clinical studies have shown that exposure to particulate air pollution is associated with increases in morbidity and mortality, and this is more evident in patients with renal diseases. However, the basis of the possible exacerbating effect of particulate air pollution on animal model of renal injury has received scant attention. Here, we assessed the effect of repeated exposure to diesel exhaust particles (DEP) on cisplatin (CP)-induced nephrotoxicity in rats. DEP (0.5 m/kg) was intratracheally (i.t.) instilled every second day for eight days (a total of five exposures). CP, 6 mg/kg was given 1 h before the third exposure to DEP. Two days following the last exposure to either DEP or saline (control), various renal endpoints were measured. Water intake, urine volume, and relative kidney weight were significantly increased in CP + DEP versus DEP and CP + saline versus saline. Plasma creatinine increased and creatinine clearance decreased in CP + DEP versus DEP and CP + saline versus saline. Interestingly, blood urea nitrogen, albumin concentrations, and gamma-glutamyl transpeptidase (GGT) activity in urine were significantly increased in DEP + CP compared with either DEP or saline + CP. The combination of DEP and CP enhanced kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, 8-isoprostane and total nitric oxide in the kidney compared with either saline + CP or DEP. Similarly, systolic blood pressure was increased in CP + DEP versus CP + saline or DEP. The renal tubular necrosis observed in kidneys of CP-treated rats was aggravated by the combination of CP + DEP. We conclude that repeated exposure to DEP potentiated CP-induced nephrotoxicity. Our data provide experimental evidence that patients with kidney injury could be at higher risk than the general population.
AB - Several epidemiological and clinical studies have shown that exposure to particulate air pollution is associated with increases in morbidity and mortality, and this is more evident in patients with renal diseases. However, the basis of the possible exacerbating effect of particulate air pollution on animal model of renal injury has received scant attention. Here, we assessed the effect of repeated exposure to diesel exhaust particles (DEP) on cisplatin (CP)-induced nephrotoxicity in rats. DEP (0.5 m/kg) was intratracheally (i.t.) instilled every second day for eight days (a total of five exposures). CP, 6 mg/kg was given 1 h before the third exposure to DEP. Two days following the last exposure to either DEP or saline (control), various renal endpoints were measured. Water intake, urine volume, and relative kidney weight were significantly increased in CP + DEP versus DEP and CP + saline versus saline. Plasma creatinine increased and creatinine clearance decreased in CP + DEP versus DEP and CP + saline versus saline. Interestingly, blood urea nitrogen, albumin concentrations, and gamma-glutamyl transpeptidase (GGT) activity in urine were significantly increased in DEP + CP compared with either DEP or saline + CP. The combination of DEP and CP enhanced kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, 8-isoprostane and total nitric oxide in the kidney compared with either saline + CP or DEP. Similarly, systolic blood pressure was increased in CP + DEP versus CP + saline or DEP. The renal tubular necrosis observed in kidneys of CP-treated rats was aggravated by the combination of CP + DEP. We conclude that repeated exposure to DEP potentiated CP-induced nephrotoxicity. Our data provide experimental evidence that patients with kidney injury could be at higher risk than the general population.
KW - Air pollution
KW - cisplatin
KW - diesel exhaust particles
KW - nephrotoxicity
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U2 - 10.1177/1535370214530249
DO - 10.1177/1535370214530249
M3 - Article
AN - SCOPUS:84907075311
SN - 1535-3702
VL - 239
SP - 1036
EP - 1044
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
IS - 8
ER -