title: Potentiation of cisplatin-induced nephrotoxicity by repeated exposure to diesel exhaust particles: An experimental study in rats.
abstract: 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.
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, UAE anemmar@uaeu.ac.ae anemmar@hotmail.com.
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Nemmar
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, UAE.
authors.forename: Sumaya
authors.initials: S
authors.lastname: Beegam
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, UAE.
authors.forename: Priya
authors.initials: P
authors.lastname: Yuvaraju
authors.affiliation: Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, UAE.
authors.forename: Javed
authors.initials: J
authors.lastname: Yasin
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, UAE.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Fahim
authors.affiliation: Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, UAE.
authors.forename: Elsadig E
authors.initials: EE
authors.lastname: Kazzam
authors.affiliation: Department of Pathology, Sultan Qaboos University Hospital, Muscat 123, Al-Khod, Sultanate of Oman.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Alhaddabi
authors.affiliation: Department of Pharmacology and Clinical Pharmacy, College of Medicine & Health Sciences, Sultan Qaboos University, Muscat 123, Al-Khod, Sultanate of Oman.
authors.forename: Badreldin H
authors.initials: BH
authors.lastname: Ali
keywords: Air pollution; cisplatin; diesel exhaust particles; nephrotoxicity