Sodium hydrogen sulfide (NaHS) ameliorates alterations caused by cisplatin in filtration slit diaphragm and podocyte cytoskeletal in rat kidney.

Asiyeh Karimi,Layasadat Khorsandi,Esrafil Mansouri,Forouzan Absalan,Armita Valizadeh

doi:10.15171/jnp.2017.26

Asiyeh Karimi, Layasadat Khorsandi + Show 3 more

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https://doi.org/10.15171/jnp.2017.26

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Abstract

Background: Hydrogen sulfide (H2S) has been shown to have a protective role in various kidney disorders. Objectives: This study investigated the molecular mechanism of NaHS (a H2S donor) in treating on the renal damage induced by cisplatin (CP).Materials and Methods: Thirty-two male rats were randomly divided into 4 groups: Normal control group (group A)‚ NaHS group (group B) which received 200 µg/kg/d (intraperitoneal injection; i.p.) for 15 days‚ CP group (group C) which rats were injected with CP (5 mg/kg, single dose, i.p.), and CP + NaHS group (group D) (5 mg/kg and 200 µg/kg, respectively, i.p.). Samples of urine and serum, tissue of kidney were collected for analysis after treatments for 15 days. Morphological changes were elevated under light microscope‚ protein expression of desmin and nephrin were determined by immunohistochemistry and western blotting and also malondialdehyde (MDA) level was determined by spectrophotometer. Results: Compared to the CP group, NaHS treatment mitigated histological damages, decreased 24-hour urine protein excretion, serum urea and creatinine as well as MDA level. NaHS treatment increased protein levels of nephrin. Moreover, NaHS treatment decreased protein levels of desmin. Conclusions: NaHS can ameliorate CP -induced renal damage in rats which is associated with the increase in nephrin protein expression, and the decrease in MDA level and desmin protein expression.

Highlights

Hydrogen sulfide (H2S) has been shown to have a protective role in various kidney disorders
Desmin protein is an intermediate filament of the cytoskeleton, which is secreted by podocytes during injury, whose its expression is remarkably correlated with podocyte injury [8,9]
The kidney weight and urine volume of rats in CP group (C group) was significantly more than rats of A and B groups (P < 0.01) whereas administration of NaHS in D group significantly improved this reduction of body weight (P < 0.01) and increased kidney weight and urine volume (P < 0.05) when compared with rats in C group (Table 1)

Summary

Introduction

Hydrogen sulfide (H2S) has been shown to have a protective role in various kidney disorders. Conclusions: NaHS can ameliorate CP -induced renal damage in rats which is associated with the increase in nephrin protein expression, and the decrease in MDA level and desmin protein expression. It has been observed that CP accumulates in the kidney with a greater degree than other organs and so renal damage is the major doselimiting side effect of this drug [2,3] The mechanism for this CP-induced renal injury has been intensively studied for years, and the results of the latest researches. The specific structure of podocytes mainly depends on the expression of cytoskeletal system components and a number of specific proteins These special protein molecules and the slit diaphragm (SD) proteins that regulate normal renal function are main portions of the podocyte barrier [4,6]. H2S because of its cytoprotective and vasodilating activity is an attractive therapeutic candidate to decrease the destructive effects of proteinuria and hypertension [15]

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