Investigation of Efficacy of Selected Drugs on Matrix Metalloproteinase MMP 2 and MMP 9 and Histone Deacetylase 2 Modulation in Experimentally Induced Diabetic Nephropathy

Abstract

Diabetes mellitus is an endocrine disorder with hyperglycemia and chronic complications affecting the eyes, blood vessels, nerves, and kidneys, causing burdens to public health. Attempts to curb it have failed. Diabetic nephropathy (DN) emerges as the prevailing microvascular complication, leading to end-stage renal disease, affecting 30% of diabetic patients, further burdening public health. This disorder manifests as persistent albuminuria and a progressive decline in the glomerular filtration rate. In diabetic nephropathy, it is common to observe pathologies such as Kimmelstiel-Wilson nodules, thickening of the glomerular basement membrane, glomerular sclerosis, and inflammation. newlineMatrix metalloproteinases (MMPs) represent a diverse family of proteolytic enzymes, possessing the ability to degrade nearly all extracellular matrix (ECM) components. Consequently, they assume a significant role in tissue remodelling. The excessive production of MMP-2 and MMP-9 plays a pivotal role in the development of diabetic nephropathy. The pathogenic features of diabetic nephropathy have been linked to a dysregulation of MMPs, which contributes to an imbalance between the production and degradation of the extracellular matrix, ultimately resulting in the development of fibrosis, a symptom commonly observed in diabetic nephropathy. Furthermore, histone deacetylase (HDAC) isoforms can regulate molecular activities in diabetes through epigenetic and post-translational regulation of transcription factors. HDAC-2 is upregulated in diabetic kidneys, making it potential therapeutic target for attenuating diabetic nephropathy. Serum creatinine and BUN levels, as well as urine albumin and creatinine levels, are used to diagnose DN. These indicators indicate the existence of structural and functional renal problems. MMPs and HDAC-2 levels are postulated in the literature as potential early markers for the development of early renal changes. newlineThe flavonoid luteolin (LT), known for its anti-inflammatory and antioxidant properties, has been