Repeated Administration of Fluvoxamine Worsens Gentamicin-induced Nephrotoxicity in Rats

authors:

avatar Afshin Ramian 1 , avatar Iraj Javadi 1 , avatar Hossein Sadeghi 2 , 3 , * , avatar Heibatollah Sadeghi 2 , 3 , avatar Esmaeel Panahi Kokhdan 2 , avatar Amir Hossein Doustimotlagh 2 , avatar Reza Abbasi 2 , avatar Sadegh Alizadeh 1 , avatar Hamed Nikbakht 1

Departemant of Toxicology, Shahreza Branch, Islamic Azad University, Shahreza, Iran
Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran
Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran

how to cite: Ramian A, Javadi I, Sadeghi H, Sadeghi H, Panahi Kokhdan E, et al. Repeated Administration of Fluvoxamine Worsens Gentamicin-induced Nephrotoxicity in Rats. J Rep Pharm Sci. 2020;9(2):e147113. https://doi.org/10.4103/jrptps.JRPTPS_57_19.

Abstract

Background: Depression is one of the most prevalent and life-threatening forms of mental disorders in chronic kidney disease. Antidepressant agents such as fluvoxamine are broadly prescribed in this situation. This study investigated the effects of fluvoxamine on gentamicin (GEN)-induced nephrotoxicity in rats. 
Materials and Methods: Twenty-four male Wistar rats were randomly divided into four groups (n = 6) including (1) control group, (2) GEN group, (3) GEN + fluvoxamine (25 mg/kg) group, and (4) GEN + fluvoxamine (50 mg/kg) group. Fluvoxamine was orally given to animals 45 min before GEN was injected (100 mg/kg, intraperitoneally [i.p.]). Blood urea nitrogen (BUN), creatinine (Cr), sodium (Na+), potassium (K+), and malondialdehyde (MDA) levels in serum were measured. Moreover, the glucose (Glu) and protein (Pro) levels in urine and the ratio of kidney to body weight (g/100 g body weight) were determined. Histopathological alterations in kidney were evaluated. 
Results: GEN significantly increased the Cr and BUN serum levels as well as urine Glu and Pro concentrations (P ≤ 0.001). Fluvoxamine exacerbated the elevation in the indicated parameters. GEN also significantly increased the serum MDA levels. Fluvoxamine had no effect on the elevated serum levels of MDA. GEN did not show any effect on the K+ and Na+ serum concentrations. Increased kidney-to-body weight ratio due to GEN nephrotoxicity was further exacerbated by 25 mg/kg of fluvoxamine (P ≤ 0.001). Pathologic findings also confirm the biochemical results. 
Conclusion: The data suggest that fluvoxamine worsens the nephrotoxicity of GEN. However, further clinical and animal investigations are required to elucidate the mechanism of this interaction.