All-trans retinoic acid has renoprotective effects on Cisplatin-induced acute kidney injury in rats.

Faten Zahran,Mohsen Khedr,Ibrahem Elsyed,Nashwa Barakat

doi:10.21608/ajbas.2020.44098.1036

Abstract

All-trans retinoic acid (ATRA) is the active metabolites of vitamin A; it has antioxidant effects, and can regulate apoptosis. This study aims to observe the effects of ATRA on cisplatin-induced acute kidney injury, where a total of 96 Sprague-Dawley rats (180–220 g) were divided into four groups; (24 rats in each); normal group, DMSO group, cisplatin group, and cisplatin with retinoic acid group. Eight rats were sacrificed on days 3, 7, and 11 in each group. Serum creatinine, blood urea nitrogen and MAU levels were assayed, the activities of Catalase (CAT), glutathione reductase (GSH) and malondialdehyde (MDA) were tested in kidney tissue, expressions of nuclear factor- kB (NF- kB), Caspase-3, and TGFβ1 were determined by real time PCR, also Histopathological changes in kidney tissue were determined. Our study found that the levels of serum creatinine, BUN, MAU, and MDA in cisplatin group were significantly increased, while the activities of CAT and GSH were significantly decreased, as well as, the expression levels of caspase-3, NF-kB, and TGFβ1 were significantly increased in cisplatin group. In contrast, ATRA group showed lower levels of serum creatinine, BUN, MAU and MDA (p < 0.05), and increased levels of CAT and GSH (p < 0.05), which reached the highest levels at day 11, also the expression levels of caspase-3, NF-kB and TGFβ1 decreased significantly in ATRA group (P< 0.05). Our study concluded that, ATRA has a protective effect on cisplatin-induced acute kidney injury in rats, and it is associated with inhibition of lipid peroxidation, lower inflammation and lower apoptosis.

Highlights

Acute kidney injury (AKI) is a rapid decrease in renal function due to kidney damage, leading to the reservation of nitrogenous compounds (Urea and Creatinine) [1]
The present results showed that there is no significant difference in the levels of serum creatinine, Blood urea nitrogen (BUN) and Microalbuminuria between control group and DMSO group
Administration of All-trans retinoic acid (ATRA) significantly decreased serum creatinine, BUN and Microalbuminuria levels at 3, 7 and 11 days (P < 0.05), which confirmed the ability of ATRA to attenuate the renal injury induced by cisplatin with the most attenuation at day 11, Table 2

Summary

Introduction

Acute kidney injury (AKI) is a rapid decrease in renal function due to kidney damage, leading to the reservation of nitrogenous compounds (Urea and Creatinine) [1]. It has been evidenced that cisplatin induce nephrotoxicity by triggering apoptosis of proximal tubular cells which is followed by inflammation and fibrosis [5], another study reported that treatment with cisplatin cause degradation of anti-apoptotic proteins such as Bcl-2 and increase the levels of pro-apoptotic proteins, such as Bax that leads to induction of apoptosis [6]. Biotransformation of cisplatin into a highly reactive form within the kidney cells is an important mechanism of cisplatin-induced AKI, where cisplatin can interact and conjugate with glutathione (thiolcontaining antioxidant molecule) [7], leading to depletion of glutathione , that means suppression of antioxidant systems, which in turn results in the formation of reactive oxygen species (ROS) and accumulation of lipid peroxidation products in kidney [8], cisplatin increased ROS through mitochondrial dysfunction and impairment of respiratory chain [9]

Methods

Results

Conclusion