The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles.
Particulate air pollution (PAP) exposure is associated with increased morbidity and mortality, particularly in patients with renal disease. However, there are only a few studies on the interaction between PAP and renal injury, and none on agents that may ameliorate it. We studied the interaction between cisplatin (CP) nephrotoxicity and a single exposure to diesel exhaust particle (DEP) in rats 24 h before sacrifice, and assessed the effect of co-treatment with the active ingredient in Nigella Sativa seed oil, thymoquinone (TQ) thereon. Rats were injected intraperitoneally with CP (6 mg/kg) and four days later, they were exposed intratracheally to DEP (0.5 mg/kg), and were sacrificed 24 h later. Oral TQ (20 mg/kg) was given daily throughout the experimental period. CP alone caused several physiological, biochemical, and histopathological changes that included reduced growth and creatinine clearance, and raised plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL-6) and C-reactive protein (CRP), creatinine and urea concentrations, and urinary N-acetyl-b-D-glucosaminidase (NAG) activities. It adversely affected several indices of oxidative damage in the kidneys, and induced renal tubular necrosis. Most of these actions were significantly potentiated in rats given both CP and DEP. TQ significantly abrogated many of the effects of CP and DEP, given alone and in combination. These results provide experimental evidence that subjects with renal diseases can be at higher risk from PAP, and that TQ, pending further pharmacological and toxicological studies, can be considered a useful agent in patients with renal diseases and exposed to PAP.
Departments of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod 123, Oman.
Badreldin H
BH
Ali
Departments of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod 123, Oman alibadreldin@hotmail.com akthmali@squ.edu.om.
Mohammed
M
Al Za'abi
Department of Pathology, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod 123, Oman.
Asem
A
Shalaby
Departments of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod 123, Oman.
Priyadarsini
P
Manoj
Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Al Khod 123, Oman.
Mostafa I
MI
Waly
Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Javed
J
Yasin
Departments of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Mohamed
M
Fahim
Departments of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Abderrahim
A
Nemmar
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000032:analysis; D002945:Cisplatin / Q000633:toxicity*; D004347:Drug Interactions; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000187:drug effects*; D008168:Lung / Q000187:drug effects*; D008297:Male; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D001335:Vehicle Emissions / Q000633:toxicity*
D000970:Antineoplastic Agents; D000975:Antioxidants; D016227:Benzoquinones; D015850:Interleukin-6; D052638:Particulate Matter; D001335:Vehicle Emissions; D002097:C-Reactive Protein; C003466:thymoquinone; D002945:Cisplatin
Cisplatin; diesel exhaust particle; nephrotoxicity; rats; thymoquinone