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Effect of infliximab, a tumor necrosis factor-alpha inhibitor, on doxorubicin-induced nephrotoxicity in rats.
Naunyn Schmiedebergs Arch Pharmacol. 2020 01; 393(1):121-130.NS

Abstract

Treatment with the chemotherapeutic agent, doxorubicin (DOX), is limited by nephrotoxicity. We investigated the possible protective effect of infliximab, a tumor necrosis factor alpha (TNF-α) inhibitor on DOX-induced nephrotoxicity. Rats were treated with a single intraperitoneal (ip) injection of DOX (17.5 mg/kg) in the absence or presence of infliximab (5 mg/kg, i.p.). Plasma and urinary markers of kidney function, oxidative stress, and inflammation were measured. Kidney and heart tissue was evaluated histopathologically. DOX-induced nephrotoxicity was confirmed by increased plasma urea, creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and clusterin concentrations. In addition, DOX increased urinary albumin/creatinine ratio, N-acetyl-β-D-glucosaminidase (NAG) activity, kidney injury molecule (KIM-1) concentrations, and reduced creatinine clearance. DOX significantly reduced renal antioxidants and increased plasma inflammatory markers and adiponectin concentrations. Concomitant treatment with infliximab did not significantly affect DOX-induced changes in plasma creatinine, cystatin C, or creatinine clearance. However, infliximab significantly reduced DOX-induced action on plasma urea, NGAL, clusterin, and adiponectin. Infliximab also significantly reduced urinary albumin/creatinine ratio, NAG activity, and KIM-1 concentrations, as well as the occurrence of fibrotic lesions in kidney tissue. Fibrosis detected in the heart was unchanged. In addition, infliximab reduced DOX-induced effects on plasma inflammatory markers, renal superoxide dismutase (SOD) and total antioxidant capacity. Our results show that infliximab is partially effective in mitigating DOX-induced nephrotoxicity in rats.

Authors+Show Affiliations

Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.Institute of Toxicology, Medical Faculty, University of Düsseldorf, Moorenstraβe 5, 40225, Düsseldorf, Germany. schupp@hhu.de.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31501914

Citation

Abdelrahman, Aly M., et al. "Effect of Infliximab, a Tumor Necrosis Factor-alpha Inhibitor, On Doxorubicin-induced Nephrotoxicity in Rats." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 393, no. 1, 2020, pp. 121-130.
Abdelrahman AM, Al Suleimani YM, Manoj P, et al. Effect of infliximab, a tumor necrosis factor-alpha inhibitor, on doxorubicin-induced nephrotoxicity in rats. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(1):121-130.
Abdelrahman, A. M., Al Suleimani, Y. M., Manoj, P., Ashique, M., Ali, B. H., & Schupp, N. (2020). Effect of infliximab, a tumor necrosis factor-alpha inhibitor, on doxorubicin-induced nephrotoxicity in rats. Naunyn-Schmiedeberg's Archives of Pharmacology, 393(1), 121-130. https://doi.org/10.1007/s00210-019-01719-x
Abdelrahman AM, et al. Effect of Infliximab, a Tumor Necrosis Factor-alpha Inhibitor, On Doxorubicin-induced Nephrotoxicity in Rats. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(1):121-130. PubMed PMID: 31501914.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of infliximab, a tumor necrosis factor-alpha inhibitor, on doxorubicin-induced nephrotoxicity in rats. AU - Abdelrahman,Aly M, AU - Al Suleimani,Yousuf M, AU - Manoj,Priyadarsini, AU - Ashique,Mohammed, AU - Ali,Badreldin H, AU - Schupp,Nicole, Y1 - 2019/09/09/ PY - 2019/05/03/received PY - 2019/08/23/accepted PY - 2019/9/11/pubmed PY - 2021/1/1/medline PY - 2019/9/11/entrez KW - Doxorubicin KW - Inflammation KW - Infliximab KW - Nephrotoxicity KW - Oxidative stress KW - TNF-α SP - 121 EP - 130 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch Pharmacol VL - 393 IS - 1 N2 - Treatment with the chemotherapeutic agent, doxorubicin (DOX), is limited by nephrotoxicity. We investigated the possible protective effect of infliximab, a tumor necrosis factor alpha (TNF-α) inhibitor on DOX-induced nephrotoxicity. Rats were treated with a single intraperitoneal (ip) injection of DOX (17.5 mg/kg) in the absence or presence of infliximab (5 mg/kg, i.p.). Plasma and urinary markers of kidney function, oxidative stress, and inflammation were measured. Kidney and heart tissue was evaluated histopathologically. DOX-induced nephrotoxicity was confirmed by increased plasma urea, creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and clusterin concentrations. In addition, DOX increased urinary albumin/creatinine ratio, N-acetyl-β-D-glucosaminidase (NAG) activity, kidney injury molecule (KIM-1) concentrations, and reduced creatinine clearance. DOX significantly reduced renal antioxidants and increased plasma inflammatory markers and adiponectin concentrations. Concomitant treatment with infliximab did not significantly affect DOX-induced changes in plasma creatinine, cystatin C, or creatinine clearance. However, infliximab significantly reduced DOX-induced action on plasma urea, NGAL, clusterin, and adiponectin. Infliximab also significantly reduced urinary albumin/creatinine ratio, NAG activity, and KIM-1 concentrations, as well as the occurrence of fibrotic lesions in kidney tissue. Fibrosis detected in the heart was unchanged. In addition, infliximab reduced DOX-induced effects on plasma inflammatory markers, renal superoxide dismutase (SOD) and total antioxidant capacity. Our results show that infliximab is partially effective in mitigating DOX-induced nephrotoxicity in rats. SN - 1432-1912 UR - https://www.unboundmedicine.com/medline/citation/31501914/Effect_of_infliximab_a_tumor_necrosis_factor_alpha_inhibitor_on_doxorubicin_induced_nephrotoxicity_in_rats_ L2 - https://dx.doi.org/10.1007/s00210-019-01719-x DB - PRIME DP - Unbound Medicine ER -