title: Nephroprotective efficacy of ceftriaxone against cisplatin-induced subchronic renal fibrosis in rats.
abstract: Cisplatin, or cis-diamminedichloridoplatinum(II), (CDDP) is a broad-spectrum antineoplastic chemotherapeutic agent with a potent efficacy against several malignancies. Its main clinical antineoplastic therapy-limiting adverse effect is nephrotoxicity, where the developments of effective nephroprotectors are needed. Therefore, the present study aimed to investigate the nephroprotective and antifibrotic potential of ceftriaxone (CTX) against CDDP-induced toxicity. Male Wister rats were treated with saline or CTX (100 or 200 mg kg-1bw) an hour before CDDP administration (1 mg kg-1bw). All the treatments were intraperitoneally administered twice weekly for consecutive 10 weeks. Twenty-four hours after last CDDP dose, blood samples were collected, then the animals were euthanized and their kidneys were isolated for measurements. CDDP significantly increased serum uric acid, urea, and creatinine contents. Toxicopathic changes showed that CDDP induced marked tubulointerstitial damage, overexpressed fibrogenic factors α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1), and down expressed cellular proliferating biomarker bromodeoxyuridine (BrdU). CTX pretreatment, particularly 200 mg/kg bw, improved the renal function biomarkers; histoarchitecture; and α-SMA, TGF-β1, and BrdU expressions. It could be concluded that CTX is endowed with antifibrotic properties and could be, therefore, used as adjuvant therapy to improve CDDP-induced nephrotoxicity. Further clinical researches are necessary to evaluate whether CTX may exhibit a new therapeutic choice for treating renal fibrotic diseases.
authors.affiliation: Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt. abdeldaim.m@vet.suez.edu.eg.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Abdel-Daim
authors.affiliation: Department of Veterinary Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, Egypt.
authors.forename: Yasser S
authors.initials: YS
authors.lastname: El-Sayed
authors.affiliation: Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Sadat City University, Sadat City, 32897, Egypt.
authors.forename: Mabrouk Abd
authors.initials: MA
authors.lastname: Eldaim
authors.affiliation: Pathology Department, College of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt.|Department of Pathology, College of Veterinary Medicine, King Faisal University, Hofuf, Saudi Arabia.
authors.forename: Abdelazim
authors.initials: A
authors.lastname: Ibrahim
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001973:Bromodeoxyuridine / Q000378:metabolism; D002443:Ceftriaxone / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin; D003404:Creatinine / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D020011:Protective Agents / Q000494:pharmacology*; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014508:Urea / Q000097:blood; D014527:Uric Acid / Q000097:blood
chemical_list: D000199:Actins; D015415:Biomarkers; D001973:Bromodeoxyuridine; D002443:Ceftriaxone; D002945:Cisplatin; D003404:Creatinine; D020011:Protective Agents; D053773:Transforming Growth Factor beta1; D014508:Urea; D014527:Uric Acid; C508962:Tgfb1 protein, rat; C498862:Acta2 protein, rat
keywords: Antifibrotic; BrdU; Ceftriaxone; Cisplatin; Fibrosis; Immunohistochemistry; Nephroprotective; Nephrotoxicity; TGF-β1; α-SMA