Ethanol and cyclophosphamide induce similar nephrotoxic effects: possible role for Nox4 and superoxide

Author(s)

Sousa, Arthur H. ^[1] ; do Vale, Gabriel T. ^{[1, 2]} ; da Silva, Carla B. P. ^{[1, 3]} ; Awata, Wanessa M. C. ^[1] ; Pinheiro, Lucas C. ^[1] ; Tirapelli, Carlos R. ^[1]

Affiliation

^[1] Univ Sao Paulo, Lab Farmacol, Escola Enfermagem Ribeirao Preto, DEPCH, Ribeirao Preto, SP - Brazil

^[2] Univ Estado Minas Gerais UEMG, Dept Ciencias Biol, Passos, MG - Brazil

^[3] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Programa Posgrad Toxicol, Passos, SP - Brazil

• Document type: Journal article
• Source: Canadian Journal of Physiology and Pharmacology; v. 99, n. 7, p. 744-751, JUL 2021.
• Web of Science Citations: 0

Abstract

We tested the hypothesis that ethanol consumption would aggravate the renal damage induced by cyclophosphamide (CYP). Male C57BL/6 J mice from control (n = 8) and CYP (n = 12) groups had free access to filtered water and standard rodent chow for 12 weeks. Then, 24 h before euthanasia mice received an intraperitoneal injection of saline or CYP (300 mg/kg). Mice from ethanol (n = 8) and CYP + ethanol (n = 12) groups had free access to increasing doses of ethanol for 12 weeks. Twenty-four hours before euthanasia, mice from ethanol and CYP + ethanol groups received an intraperitoneal injection of saline or CYP, respectively. Ethanol, CYP, or the association of both drugs augmented serum levels of creatinine and increased the levels of superoxide (O-2(center dot)) generation and thiobarbituric acid reactive substances in the renal cortex. Upregulation of Nox4 and increased activity of superoxide dismutase were detected in the renal cortex of mice treated with ethanol, CYP, or the combination of these drugs; however, these molecular alterations induced by CYP were not potentiated by ethanol consumption. Our findings revealed that chronic ethanol consumption had no potentiating effect on the nephrotoxic effects displayed by CYP. It is possible that the combination of these drugs showed no synergistic effect because they share the same molecular mechanisms of renal toxicity. (AU)

• FAPESP's process: 17/24123-5 - Impact of chronic ethanol consumption in the cardiac and vascular damages induced by experimental sepsis: evaluation of the role of iNOS
• Grantee: Carlos Renato Tirapelli
• Support Opportunities: Regular Research Grants