Hesperidin protects against aluminum-induced renal injury in rats via modulating MMP-9 and apoptosis: biochemical, histological, and ultrastructural study

Abstract

Aluminum, one of the most abundant metallic elements, is known to be toxic to multiple organs including the kidneys. This study aimed to investigate the pleiotropic nephroprotective effects of Hesperidin in aluminum chloride (ALCL3)-induced renal injury, highlighting the potential molecular mechanisms underlying. Twenty-four male albino rats were divided into four groups: control, Hesperidin (80 mg/kg BW, orally), ALCL3 (10 mg/kg BW, IP), and ALCL3 + Hesperidin groups. By the end of the study, blood samples were collected, and tissue samples were harvested at sacrifice. ALCL3 rats showed dramatically declined renal function, enhanced intrarenal oxidative stress, inflammation, apoptosis, and extravagant renal histopathological damage with interstitial fibrosis as shown by a higher Endothelial, Glomerular, Tubular, and Interstitial (EGTI) score. Hesperidin significantly reversed all the aforementioned detrimental effects in ALCL3-treated rats. The study verified the nephroprotective effects of Hesperidin on ALCL3-induced renal damage and confirmed the critical role of extracellular matrix (ECM) remodeling and apoptosis inhibition. Graphical Abstract

Immuno-antioxidative reno-modulatory effectiveness of Echinacea purpurea extract against bifenthrin-induced renal poisoning

“…Kidney samples were hydrated in ascending grades of ethanol, cleared in xylene, and embedded in paraffin. Sections of 5 μm thick were cut and stained with hematoxylin and eosin for histological examination under light microscopy 21 .…”

Recent understanding of the mechanisms of the biological activities of hesperidin and hesperetin and their therapeutic effects on diseases

“… [ 155 ] Renal injury Hsd Aluminum-induced rats Inhibit the MMP-9-related signaling pathway activated by ALCL3. [ 138 ] Renal injury Hsd sodium fluoride-induced rats Inhibit PI3K/Akt/mTOR pathway. [ 156 ] Anti-inflammatory Postmenopausal osteoporosis Hsd Ovariectomized mice Ovariectomized rats Inhibition of osteoclast superoxide reduces bone Resorption.…”

“…Hesperidin has also been shown to protect rats against acrylamide-induced nephrotoxicity, oxidative stress, lipid peroxidation and DNA damage [ 137 ]. Hesperidin modulates MMP-9 expression and apoptosis and protects against Al-induced kidney damage in rats [ 138 ] and acute As-induced liver and kidney injury in mice [ 139 ]. Transforming growth factor β1 upregulation in hypertensive rats is associated with endothelial dysfunction and remodeling.…”

“…Transforming growth factor β-stimulated pericyte myofibroblast differentiation and proliferation induces kidney damage and fibrosis. Hesperidin significantly reduces serum ACE and plasma TGF-β1 activity and downregulates renal angiotensin II receptor type 1 (AT1) [ 138 ]. Thus, hesperidin prevents L-NAME-induced hypertension, vascular and renal dysfunction, renal artery remodeling, glomerular ECM accumulation and renal fibrosis.…”