<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Diabetes patients are more prone to acute kidney injury (AKI). Endopeptidases known as matrix metalloproteinases (MMPs) cause extracellular matrix destruction and are responsible for ischemic organ damage. Diabetic nephropathy (DN) affects almost one third of all diabetic patients. MMP-2 and MMP-9 lead to the breakdown of the basement membrane of the glomeruli and thereby the advancement of ischemic injury in diabetes. In addition, histone deacetylase-2 (HDAC-2) is the primary regulator of important signalling processes in the diabetic kidney. A possible treatment approach for diabetic kidney preservation is the flavonoid luteolin (LT), which has anti-inflammatory and antioxidant effects. Our aim was to investigate the renoprotective potential of LT in diabetes by modulating MMP-2, MMP-9 and HDAC-2 activity. The expression of MMP-2, MMP-9 and HDAC-2 were statistically higher in streptozotocin-induced diabetic rat renal homogenate after renal ischemic reperfusion injury. These changes were reversed with 2 weeks of pre-treatment with LT (50 mg/kg po). In diabetic rats, pre-treatment with LT significantly reduced oxidative stress, inflammation and fibrosis compared to control animals. Preventive LT prior to renal ischemia showed improvement in body weight, kidney weight/body weight ratio, reversal of renal injury and biochemical changes with lower activity of malondialdehyde (MDA), myeloperoxidase (MPO), hydroxyproline (HP), pathological damage and fibrosis in renal tissue. Our data imply that LT prevents DN in rats by inhibiting MMP-2, MMP-9 and HDAC-2 expression, as well as by lowering the indices of oxidative stress, pro-inflammatory factors and fibrosis.</p>
</abstract>

Diabetes patients are more prone to acute kidney injury (AKI). Endopeptidases known as matrix metalloproteinases (MMPs) cause extracellular matrix destruction and are responsible for ischemic organ damage. Diabetic nephropathy (DN) affects almost one third of all diabetic patients. MMP-2 and MMP-9 lead to the breakdown of the basement membrane of the glomeruli and thereby the advancement of ischemic injury in diabetes. In addition, histone deacetylase-2 (HDAC-2) is the primary regulator of important signalling processes in the diabetic kidney. A possible treatment approach for diabetic kidney preservation is the flavonoid luteolin (LT), which has anti-inflammatory and antioxidant effects. Our aim was to investigate the renoprotective potential of LT in diabetes by modulating MMP-2, MMP-9 and HDAC-2 activity. The expression of MMP-2, MMP-9 and HDAC-2 were statistically higher in streptozotocin-induced diabetic rat renal homogenate after renal ischemic reperfusion injury. These changes were reversed with 2 weeks of pre-treatment with LT (50 mg/kg po). In diabetic rats, pre-treatment with LT significantly reduced oxidative stress, inflammation and fibrosis compared to control animals. Preventive LT prior to renal ischemia showed improvement in body weight, kidney weight/body weight ratio, reversal of renal injury and biochemical changes with lower activity of malondialdehyde (MDA), myeloperoxidase (MPO), hydroxyproline (HP), pathological damage and fibrosis in renal tissue. Our data imply that LT prevents DN in rats by inhibiting MMP-2, MMP-9 and HDAC-2 expression, as well as by lowering the indices of oxidative stress, pro-inflammatory factors and fibrosis.

Luteolin alleviates renal ischemia-reperfusion injury in streptozotocin induced diabetic rats by inhibiting metalloenzymes expression

Department of Pharmacology, Institute of Pharmacy

Current Issues in Pharmacy and Medical Sciences

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Diabetes patients are more prone to acute kidney injury (AKI). Endopeptidases known as matrix metalloproteinases (MMPs) cause extracellular matrix destruction...

Luteolin alleviates renal ischemia-reperfusion injury in streptozotocin induced diabetic rats by inhibiting metalloenzymes expression

Published Online: Dec 25, 2023

Page range: 199 - 206

Received: Jun 18, 2023

Accepted: Oct 09, 2023

DOI: https://doi.org/10.2478/cipms-2023-0035

Keywords
luteolin, MMPs, renal ischemia reperfusion, diabetic nephropathy, HDAC-2

© 2023 Rakesh B. Daude et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Luteolin alleviates renal ischemia-reperfusion injury in streptozotocin induced diabetic rats by inhibiting metalloenzymes expression

Published Online: Dec 25, 2023

Page range: 199 - 206

Received: Jun 18, 2023

Accepted: Oct 09, 2023

DOI: https://doi.org/10.2478/cipms-2023-0035

Keywordsluteolin, MMPs, renal ischemia reperfusion, diabetic nephropathy, HDAC-2

© 2023 Rakesh B. Daude et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords
luteolin, MMPs, renal ischemia reperfusion, diabetic nephropathy, HDAC-2