Restoring glomerular filtration rate by sulforaphane modulates ERK1/2/JNK/p38MAPK, IRF3/iNOS, Nrf2/HO-1 signaling pathways against folic acid-induced acute renal injury in rats

Folic acid (FA)-induced acute renal injury (AKI) is a commonly and highly reproducible model used to study AKI. The current study aims to evaluate the possible protective effects of sulforaphane (SFN) against FA-induced renal damage and explore the underlying molecular mechanism. The animals were divided into four groups (6 rats/group) as follows: normal group (received vehicle, p.o.), FA group (received 250 mg/kg, i.p.), SFN low dose group (received 15 mg/kg, p.o. plus FA 250 mg/kg, i.p.), SFN high dose group (30 mg/kg, p.o. plus FA 250 mg/kg, i.p.). At the end of the experiment, serum samples and kidney tissues were obtained to perform biochemical, molecular, and histopathological investigations. The present study showed that FA-caused AKI was confirmed by a significant elevation of kidney function biomarkers serum levels accompanied by an observation of histopathologic changes. Interestingly, SFN-administration significantly improved kidney function, reduced oxidative stress markers; MDA, NADPH oxidase, MPO, iNOS with up-regulation of GSH, GCLM, GPX4, SOD, NQO1, HO-1 and Nrf2 levels. SFN also downregulated proinflammatory markers. The results also demonstrated the anti-apoptotic effect of SFN through its ability to increase the antiapoptotic Bcl-2 protein and to decrease caspase-3. Moreover, SFN significantly decreased the relative expression of JNK, ERK-1/2, IRF3, and p38MAPK as compared to the FA-nephrotoxic group. The present study revealed that SFN possess an antioxidant, anti-inflammatory and antiapoptotic activity by modulating caspase-3, Bcl-2, ERK1/2, JNK, GCLM, NQO1, GPX4, Nrf2, HO-1 and P38 signaling pathways in a dose dependent manner which provides a potential therapeutic strategy for preventing FA-induced AKI.