Amelioration of cisplatin-induced rat renal lesions by a cyclooxygenase (COX)-2 selective inhibitor

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2012-09, Vol.64 (6), p.625-631
• Main Authors: Yamamato, Emi, Izawa, Takeshi, Sawamoto, Osamu, Juniantito, Vetnizah, Kuwamura, Mitsuru, Yamate, Jyoji
• Format: Article
• Language: English
• Subjects: Actin; Acute Kidney Injury - chemically induced; Acute Kidney Injury - pathology; Acute Kidney Injury - prevention & control; Animals; Antineoplastic Agents - toxicity; Biological and medical sciences; Blood; Cisplatin; Cisplatin - toxicity; Cisplatin-induced renal failure; COX-2; Creatinine; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase-2; Epithelial cells; Fibrosis; Gene expression; Immunohistochemistry; Inflammation; Investigative techniques, diagnostic techniques (general aspects); Kidney; Kidney - drug effects; Kidney - pathology; Macrophage; Macrophages; Male; Medical sciences; messenger RNA; Muscles; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Nitrobenzenes - pharmacology; Nitrogen; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; PGE2; prostaglandin synthase; Rats; Rats, Inbred F344; Real-Time Polymerase Chain Reaction; Renal failure; Reverse Transcriptase Polymerase Chain Reaction; Sulfonamides - pharmacology; TGF-β1; transforming growth factor beta 1; Urea; urea nitrogen
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1016/j.etp.2010.12.005

Cyclooxygenase (COX)-2, an inducible form of COX, plays important roles in inflammatory lesions. We investigated effects of a COX-2 selective inhibitor, NS-398, on cisplatin (CDDP)-induced rat renal lesions. As compared with rats injected with a single dose of CDDP (6mg/kg; CDDP group), rats who were treated everyday with NS-398 (3mg/kg) after the CDDP injection (inhibitor group), showed the declines of blood urea nitrogen and creatinine values, and the delay of the peak of regenerating renal epithelial cell number (demonstrable with 5′-bromo-2′-deoxyuridine immunohistochemistry); these findings suggested cytoprotective effects of the inhibitor. Furthermore, the numbers of ED1-immunopositive macrophages and α-smooth muscle actin (α-SMA)-immunopositive myofibroblasts were lower in the inhibitor group than in the CDDP group; mRNA expression of transforming growth factor-β1 (TGF-β1) was also decreased in the inhibitor group. Because the fibrotic area seen after CDDP injection were tended to decrease in the inhibitor group compared with the CDDP group, it was considered that the decreased number of infiltrating macrophages by the inhibitor might lead to the decreased production of TGF-β1, thereby resulting in the reduced number of α-SMA-positive myofibroblasts responsible for fibrosis. Collectively, although these differences between the CDDP and inhibitor groups were not always marked, the COX-2 inhibitor used in this study could ameliorate the CDDP-induced rat renal lesions.