Pentoxifylline May Restore Kanamycin-Induced Renal Damage in Rats

Authors

  • Orhan Corum Department of Pharmacology and Toxicology, Veterinary Faculty, Selcuk University. 42031 Konya, Turkey.
  • Ozgur Ozdemir Department of Pharmacology and Toxicology, Veterinary Faculty, Selcuk University. 42031 Konya, Turkey.
  • Mustafa Hitit Department of Pharmacology and Toxicology, Veterinary Faculty, Selcuk University. 42031 Konya, Turkey.
  • Duygu Durna Corum Department of Pharmacology and Toxicology, Veterinary Faculty, Selcuk University. 42031 Konya, Turkey.
  • Devran Coskun Department of Pharmacology and Toxicology, Veterinary Faculty, Selcuk University. 42031 Konya, Turkey.
  • Ayse Er Department of Pharmacology and Toxicology, Veterinary Faculty, Selcuk University. 42031 Konya, Turkey.

DOI:

https://doi.org/10.22456/1679-9216.84836

Abstract

Background: Kidney damage can be caused by many factors, such as using certain drugs in high doses or over the long
term. The use of one such group of drugs, aminoglycosides, which act as Gram-negative antibacterial therapeutic agents,
can lead to nephrotoxicity. It has been hypothesized that aminoglycoside-induced nephrotoxicity might be prevented by
using pentoxifylline, which has antioxidant and anti-inflammatory effects and improves microcirculation. The objective
of this present research was to determine the protective effects of pentoxifylline on kanamycin-induced kidney damage.
Materials, Methods & Results: Thirty-two male Wistar rats were divided into four groups as follows: control, pentoxifylline,
kanamycin, and kanamycin + pentoxifylline. The control group received intraperitoneal (IP) injections of 0.5 mL normal
saline solution once a day (d) (SID) for 20 d; the pentoxifylline group received IP injections of 50 mg/kg pentoxifylline
twice a day (BID) for 20 d, the kanamycin group received subcutaneous (SC) injections of 500 mg/kg kanamycin SID for
20 d, and the kanamycin + pentoxifylline group received both SC injections of 500 mg/kg kanamycin SID and IP injections
of 50 mg/kg pentoxifylline BID for 20 d. At the end of 20 d, blood samples were taken from the heart by cardiac puncture
under general anesthesia. After euthanizing the rats by cervical dislocation under anesthesia, the kidneys were immediately
removed, relative kidney weights were calculated, and routine pathologic evaluations were conducted. Hemogram
parameters were measured using a blood cell count apparatus and serum biochemical parameters were measured using
an autoanalyzer. Kanamycin also caused (P < 0.05) tubular degeneration and tubular dilatation. Although pentoxifylline
significantly reduced the level of kanamycin-induced tubular degeneration (P < 0.05), it did not significantly reduce tubular
dilatation. Increases in relative kidney weights (P < 0.05) and in interstitial mononuclear cell (MNC) infiltrates were
observed in the kanamycin and kanamycin + pentoxifylline groups compared to those in the control and pentoxifylline
groups. Statistically significant changes were determined in the levels of some hemogram and biochemical parameters
within reference ranges (P < 0.05).
Discussion: In this study, both tubular degeneration and dilatation were observed in the kanamycin group. Pentoxifylline
inhibited (P < 0.05) kanamycin-induced tubular degeneration and appeared to also reduce tubular dilatation, although this
reduction was not significant. Tubular necrosis, epithelial edema of proximal tubules, tubular fibrosis, and perivascular
inflammation might also be observed in aminoglycoside-induced nephrotoxicity. In current research, pentoxifylline prevented
tubular damage induced by kanamycin, but did not inhibit infiltration by MNCs. Pentoxifylline also ameliorated
amikacin- or gentamycin-induced histopathologic changes, especially those associated with tubular structures. The protective
effects of pentoxifylline on kanamycin-induced tubular nephrotoxicity in this research might be a result of its stimulating
the production of prostaglandin, a vasodilator, and of its improving microcirculation. Although the anti-inflammatory
effects of pentoxifylline have been reported, these did not inhibit kanamycin-induced infiltration by interstitial MNCs in
the present study. These results could indicate that the anti-inflammatory effects of pentoxifylline are not obvious and/or
are dose dependent. Statistically significantly changes were determined in the levels of some hemogram and biochemical
parameters in reference ranges. However, these changes were within the reference ranges for rats. These results suggested
that kanamycin-induced tubular degeneration and dilatation might be prevented by administering pentoxifylline.

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Published

2018-01-01

How to Cite

Corum, O., Ozdemir, O., Hitit, M., Corum, D. D., Coskun, D., & Er, A. (2018). Pentoxifylline May Restore Kanamycin-Induced Renal Damage in Rats. Acta Scientiae Veterinariae, 46(1), 7. https://doi.org/10.22456/1679-9216.84836

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