title: Effects of pre and post-treatments with dipyridamole in gentamicin-induced acute nephrotoxicity in the rat.
abstract: This study investigated the pretreatment and post-treatment effects of dipyridamole (20 mg/kg/day, p.o.) in gentamicin-induced acute nephrotoxicity in rats. Rats were administered gentamicin (100 mg/kg/day, i.p.) for 8 days. Gentamicin-administered rats exhibited renal structural and functional changes as assessed in terms of a significant increase in serum creatinine and urea and kidney weight to body weight ratio as compared to normal rats. Renal histopathological studies revealed a marked incidence of acute tubular necrosis in gentamicin-administered rats. These renal structural and functional abnormalities in gentamicin-administered rats were accompanied with elevated serum uric acid level, and renal inflammation as assessed in terms of decrease in interleukin-10 levels. Dipyridamole pretreatment in gentamicin-administered rats afforded a noticeable renoprotection by markedly preventing renal structural and functional abnormalities, renal inflammation and serum uric acid elevation. On the other hand, dipyridamole post-treatment did not significantly prevent uric acid elevation and renal inflammation, and resulted in comparatively less protection on renal function although it markedly reduced the incidence of tubular necrosis. In conclusion, uric acid elevation and renal inflammation could play key roles in gentamicin-nephrotoxicity. Dipyridamole pretreatment markedly prevented gentamicin-induced acute nephrotoxicity, while its post-treatment resulted in comparatively less renal functional protection.
authors.affiliation: Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia. Electronic address: pbala2006@gmail.com.
authors.forename: Pitchai
authors.initials: P
authors.lastname: Balakumar
authors.affiliation: Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Wei Ern
authors.initials: WE
authors.lastname: WitnessKoe
authors.affiliation: Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Yi Syen
authors.initials: YS
authors.lastname: Gan
authors.affiliation: Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Soo Mei
authors.initials: SM
authors.lastname: JemayPuah
authors.affiliation: Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Kuganesswari
authors.affiliation: Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Prajapati
authors.affiliation: Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Rajavel
authors.initials: R
authors.lastname: Varatharajan
authors.affiliation: Faculty of Medicine, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Sam Annie
authors.initials: SA
authors.lastname: Jayachristy
authors.affiliation: Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Karupiah
authors.initials: K
authors.lastname: Sundram
authors.affiliation: Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia.
authors.forename: Mohd Baidi
authors.initials: MB
authors.lastname: Bahari
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D019610:Cytoprotection; D004176:Dipyridamole / Q000494:pharmacology*; D004195:Disease Models, Animal; D005839:Gentamicins; D016753:Interleukin-10 / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007683:Kidney Tubular Necrosis, Acute / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*; D008297:Male; D009393:Nephritis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014527:Uric Acid / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D005839:Gentamicins; D016753:Interleukin-10; D014527:Uric Acid; D004176:Dipyridamole; D003404:Creatinine
keywords: Acute nephrotoxicity; Dipyridamole; Gentamicin; Renal dysfunction; Renal inflammation; Renoprotection