title: Combination of tadalafil and diltiazem attenuates renal ischemia reperfusion-induced acute renal failure in rats.
abstract: Life threatening conditions characterized by renal ischemia/reperfusion (RIR) such as kidney transplantation, partial nephrectomy, renal artery angioplasty, cardiopulmonary bypass and aortic bypass surgery, continue to be among the most frequent causes of acute renal failure. The current study investigated the possible protective effects of tadalafil alone and in combination with diltiazem in experimentally-induced renal ischemia/reperfusion injury in rats. Possible underlying mechanisms were also investigated such as oxidative stress and inflammation. Rats were divided into sham-operated and I/R-operated groups. Anesthetized rats (urethane 1.3g/kg) were subjected to bilateral ischemia for 30min by occlusion of renal pedicles, then reperfused for 6h. Rats in the vehicle I/R group showed a significant (p˂0.05) increase in kidney malondialdehyde (MDA) content; myeloperoxidase (MPO) activity; TNF-α and IL-1β contents. In addition significant (p˂0.05) increase in intercellular adhesion molecule-1(ICAM-1) content, BUN and creatinine levels, along with significant decrease in kidney superoxide dismutase (SOD) activity. In addition, marked diffuse histopathological damage and severe cytoplasmic staining of caspase-3 were detected. Pretreatment with combination of tadalafil (5mg/kg bdwt) and diltiazem (5mg/kg bdwt) resulted in reversal of the increased biochemical parameters investigated. Also, histopathological examination revealed partial return to normal cellular architecture. In conclusion, pretreatment with tadalafil and diltiazem combination protected against RIR injury.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
authors.forename: Alaa E
authors.initials: AE
authors.lastname: El-Sisi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
authors.forename: Samia S
authors.initials: SS
authors.lastname: Sokar
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
authors.forename: Sally E
authors.initials: SE
authors.lastname: Abu-Risha
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt. Electronic address: hanaaadel_2011@yahoo.com.
authors.forename: Hanaa A
authors.initials: HA
authors.lastname: Ibrahim
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004110:Diltiazem / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury / Q000097:blood / Q000150:complications*; D013482:Superoxide Dismutase / Q000378:metabolism; D000068581:Tadalafil / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D008315:Malondialdehyde; D000068581:Tadalafil; D003404:Creatinine; D009195:Peroxidase; D013482:Superoxide Dismutase; D004110:Diltiazem
keywords: Caspase-3; ICAM-1; IL-Iβ; Oxidative stress; Renal ischemia/reperfusion; TNF-α