Diosmin Mitigates Gentamicin-Induced Nephrotoxicity in Rats: Insights on miR-21 and -155 Expression, Nrf2/HO-1 and p38-MAPK/NF-κB Pathways
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....
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MDPI AG
2023-01-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/11/1/48 |
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| author | Rania I. Nadeem Amany S. Aboutaleb Nancy S. Younis Hebatalla I. Ahmed |
| author_facet | Rania I. Nadeem Amany S. Aboutaleb Nancy S. Younis Hebatalla I. Ahmed |
| author_sort | Rania I. Nadeem |
| collection | DOAJ |
| description | 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. |
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| language | English |
| last_indexed | 2024-03-09T11:06:28Z |
| publishDate | 2023-01-01 |
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| record_format | Article |
| series | Toxics |
| spelling | doaj.art-c0f7785a4a69447e9cbc88dbe87020cb2023-12-01T00:55:39ZengMDPI AGToxics2305-63042023-01-011114810.3390/toxics11010048Diosmin Mitigates Gentamicin-Induced Nephrotoxicity in Rats: Insights on miR-21 and -155 Expression, Nrf2/HO-1 and p38-MAPK/NF-κB PathwaysRania I. Nadeem0Amany S. Aboutaleb1Nancy S. Younis2Hebatalla I. Ahmed3Pharmacology and Toxicology Department, Faculty of Pharmacy, Heliopolis University, Cairo 11785, EgyptPharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, EgyptPharmaceutical Sciences Department, Faculty of Clinical Pharmacy, King Faisal University, Al-Ahsa, Al-Hofuf 31982, Saudi ArabiaPharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, EgyptGentamicin (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.https://www.mdpi.com/2305-6304/11/1/48diosmingentamicinnephrotoxicitymiR-21miR-155p38-MAPK |
| spellingShingle | Rania I. Nadeem Amany S. Aboutaleb Nancy S. Younis Hebatalla I. Ahmed Diosmin Mitigates Gentamicin-Induced Nephrotoxicity in Rats: Insights on miR-21 and -155 Expression, Nrf2/HO-1 and p38-MAPK/NF-κB Pathways Toxics diosmin gentamicin nephrotoxicity miR-21 miR-155 p38-MAPK |
| title | Diosmin Mitigates Gentamicin-Induced Nephrotoxicity in Rats: Insights on miR-21 and -155 Expression, Nrf2/HO-1 and p38-MAPK/NF-κB Pathways |
| title_full | Diosmin Mitigates Gentamicin-Induced Nephrotoxicity in Rats: Insights on miR-21 and -155 Expression, Nrf2/HO-1 and p38-MAPK/NF-κB Pathways |
| title_fullStr | Diosmin Mitigates Gentamicin-Induced Nephrotoxicity in Rats: Insights on miR-21 and -155 Expression, Nrf2/HO-1 and p38-MAPK/NF-κB Pathways |
| title_full_unstemmed | Diosmin Mitigates Gentamicin-Induced Nephrotoxicity in Rats: Insights on miR-21 and -155 Expression, Nrf2/HO-1 and p38-MAPK/NF-κB Pathways |
| title_short | Diosmin Mitigates Gentamicin-Induced Nephrotoxicity in Rats: Insights on miR-21 and -155 Expression, Nrf2/HO-1 and p38-MAPK/NF-κB Pathways |
| title_sort | diosmin mitigates gentamicin induced nephrotoxicity in rats insights on mir 21 and 155 expression nrf2 ho 1 and p38 mapk nf κb pathways |
| topic | diosmin gentamicin nephrotoxicity miR-21 miR-155 p38-MAPK |
| url | https://www.mdpi.com/2305-6304/11/1/48 |
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