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

Abstract

All-trans retinoic acid (ATRA) is the active metabolites of vitamin A; it has antioxidant effects, and can regulate apoptosis. The present study aims to observe the effectiveness of ATRA on acute kidney injury induced by cisplatin, where a total of 96 Sprague-Dawley rats (180-220 g) were subdivided into four groups; (24 in each group); 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. Blood, urine and kidney tissue samples were collected for the determination of serum creatinine, blood urea nitrogen, MAU, and kidney tissue malondialdehyde (MDA), Catalase (CAT), glutathione reductase (GSH) levels, also for determination of the expression levels of nuclear factor-kB (NF-kB), Caspase-3, and TGFβ1, as well as histological examination.Serum creatinine, BUN, MAU, and MDA levels 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 compared with those in normal and DMSO groups. 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). In conclusion, ATRA has a protective effect on acute kidney injury induced by cisplatin in rats, and it plays an important role in decreasing of apoptosis, inflammation, and inhibition of lipid peroxidation.

Possible Underlying Mechanisms for the Renoprotective Effect of Retinoic Acid-Pretreated Wharton’s Jelly Mesenchymal Stem Cells against Renal Ischemia/Reperfusion Injury

“…Rats were allocated to five groups (n = 18 rats) as follows: (I) Sham group: Rats underwent right nephrectomy with the exposure of the left kidney without clamping its pedicle; (II) IRI group, a sham group with the left renal pedicle clamping for 45 min [3]; (III) ATRA group, an IRI group with intravenous injection of 10 µM ATRA in 150 µL of complete growth medium after the release of the vascular clamp after 10 min [19]; (IV) WJ-MSCs group, an IRI group II with intravenous administration of 7 × 10 6 WJ-MSCs suspended in 150 µL complete medium via the penile vein following vascular clamp release after 10 min [20]; (V) WJ-MSCs + ATRA group (n = 18), an IRI injury was induced similar to group II followed by intravenous administration of 150 µL of 7 × 10 6 WJ-MSCs pretreated with 10 µM ATRA) [20]. Each group was subdivided into three subgroups, each with six rats, according to the time of sacrifice: three days, five days, and seven days after the surgery.…”