Diosmin Mitigates Gentamicin-Induced Nephrotoxicity in Rats: Insights on miR-21 and -155 Expression, Nrf2/HO-1 and p38-MAPK/NF-κB Pathways

Abstract

Gentamicin (GNT) is the most frequently used aminoglycoside. However, its therapeutic efficacy is limited due to nephrotoxicity. Thus, the potential anticipatory effect of Diosmin (DIOS) against GNT-prompted kidney damage in rats together with the putative nephroprotective pathways were scrutinized. Four groups of rats were used: (1) control; (2) GNT only; (3) GNT plus DIOS; and (4) DIOS only. Nephrotoxicity was elucidated, and the microRNA-21 (miR-21) and microRNA-155 (miR-155) expression and Nrf2/HO-1 and p38-MAPK/NF-κB pathways were assessed. GNT provoked an upsurge in the relative kidney weight and serum level of urea, creatinine, and KIM-1. The MDA level was markedly boosted, with a decline in the level of TAC, SOD, HO-1, and Nrf2 expression in the renal tissue. Additionally, GNT exhibited a notable amplification in TNF-α, IL-1β, NF-κB p65, and p38-MAPK kidney levels. Moreover, caspase-3 and BAX expression were elevated, whereas the Bcl-2 level was reduced. Furthermore, GNT resulted in the down-regulation of miR-21 expression along with an up-regulation of the miR-155 expression. Histological examination revealed inflammation, degradation, and necrosis. GNT-provoked pathological abnormalities were reversed by DIOS treatment, which restored normal kidney architecture. Hence, regulating miR-21 and -155 expression and modulating Nrf2/HO-1 and p38-MAPK/NF-κB pathways could take a vital part in mediating the reno-protective effect of DIOS.

Punicalagin Opposes Gentamicin Nephrotoxicity in Rats: Role of Nrf2 and NF-κB Pathways

“…6 In agreement with previous studies, the current investigation demonstrated that GEN insult resulted in a significant decrease of Nrf2, associated with a significant increase of NF-κB p65 in rat kidneys. 8,9 The current study also revealed that PNG treatment significantly restored the balance between the two pathways, as indexed by the significant increment of Nrf2, and the significant decrement of NF-κB p65 in kidneys of GEN-challenged rats. Similarly, prior investigations showed that PNG protected against oxidative stress, inflammation, and apoptosis through upregulation of Nrf2 pathway and inhibition of NF-κB pathway.…”

“…6,7 Previous investigations showed that GEN-induced renal toxicity caused by a marked disruption in the balance between Nrf2 and NF-κB pathways resulting in augmented oxidative stress, inflammatory responses, and cell apoptosis. 8,9 Punicalagin (PNG) is a biologically active polyphenolic ingredient obtained from pomegranate (Punica granatum). It was reported that PNG had antioxidant, anti-inflammatory, and antiapoptotic properties.…”

Renal mitochondrial restoration by gymnemic acid in gentamicin-mediated experimental nephrotoxicity: evidence from serum, kidney and histopathological alterations

“…However, diosmin (100 mg/kg) prompted minimal inflammatory cell infiltration into the renal tubule cortex. The anti-inflammatory compound diosmin reduced the count of TNF-α, IL-1β, p38 mitogen-activated protein kinase (p38MAPK), and nuclear factor kappa B (NF-ĸB) cells ( Nadeem et al, 2023 ). Consistent with the current findings, Haghighi et al (2012) reported a decrease in animal body weight following nephrotoxicity.…”

Connection between Radiation-Regulating Functions of Natural Products and miRNAs Targeting Radiomodulation and Exosome Biogenesis

“…Chrysin [175] miR-92a-3p [176], let-7a-5p, miR-9-5p, miR-22-3p [177], miR-34a-5p [177,178], miR-126-3p [177] Chlorogenic acid [179] miR-199a-5p [180] miR-18a-5p [177], miR-21-5p [181,182], miR-221-3p [177] ↓ Daidzein [5] miR-122-5p [183] Diosmin [184] miR-21-5p [181,182] Delphinidin [185] miR-23a-3p [186], miR-204-3p [187] miR-155-5p [181], miR-17-5p [188] ↓ Epigallocatechin gallate (EGCG) [189] miR-30a-5p [190] Melatonin [191] miR-155-5p [192], miR-23a-3p [193] ↓…”