Reno-protective effects of ursodeoxycholic acid against gentamicin-induced nephrotoxicity through modulation of NF-κB, eNOS and caspase-3 expressions

Abstract

Gentamicin (GNT) is a potent aminoglycoside antibiotic widely used to treat life-threatening bacterial infections. We aim to investigate the potential protective effect of ursodeoxycholic acid (UDCA) against GNT-induced nephrotoxicity. In this study, 24 male Wistar rats were used and randomly divided into four groups of six animals each. Control group received 0.5% carboxymethyl cellulose orally for 15 days, GNT group received GNT 100 mg/kg/day i.p. for 8 days, UDCA group received UDCA orally for 15 consecutive days at a dose of 60 mg/kg/day suspended in 0.5% carboxymethyl cellulose and UDCA-pretreated group received UDCA orally for 7 days then co-administered with GNT i.p. for 8 days at the same fore-mentioned doses. Serum levels of kidney function parameters (urea, creatinine, uric acid and albumin) were measured. Renal tissues were used to evaluate oxidative stress markers; malonaldehyde (MDA), reduced glutathione (GSH) and the anti-oxidant enzyme superoxide dismutase (SOD) activities and nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and kidney injury molecule-1 (KIM-1) mRNA levels. Immunohistochemical expression of endothelial nitric oxide synthase (eNOS) and caspase-3 and histological and ultrastructural examination were performed. Treatment with GNT increased the serum levels of renal function parameters and renal MDA, NF-κB and KIM-1 mRNA levels, while it decreased GSH and SOD activities. Marked immunohistochemical expression of caspase-3 was observed after GNT administration while it decreased eNOS expression. Histological and ultrastructural alterations were also evident in renal corpuscles and tubules. In contrast, pretreatment with UDCA reversed changes caused by GNT administration. These results suggest that UDCA ameliorates GNT-induced kidney injury via inhibition of oxidative stress, inflammation and apoptosis.

Effect of dimethyl sulfoxide in combat with gentamicin induced nephrotoxicity in rats

“…After GS administration, necrotic tubular cells and proteins excreted by tubular cells (Tamm-Horsfall protein) makes tubular cast in that maybe leads to tubular occlusion. In our study similar to other researches administration of different antioxidants reduced tubular cast significantly against GS nephrotoxicity (14,29).…”

“…In our research, serum MDA was increased by GS similar to other reports (27,28). Similar to our study, the other researchers reported improvement of serum MDA against GS nephrotoxicity with administration of different antioxidants (13,17,27,29). The elevated serum MDA shows intensification of free radicals production or lipid peroxidation.…”

A Complementary Herbal Product for Controlling Giardiasis

“…Moreover, Sun et al showed that artesunate, an A. annua ingredient, induced apoptosis of lamina propria macrophages and dendritic cells and decreased mucosal expression of TNF-α in a rodent model of colitis [ 83 ]. Numerous studies have associated NF-kB and TNF-α with various inflammatory conditions [ 84 , 85 ]. Therefore, controlling the activation of NF-kB and expression of TNF-α could account for the curative effect of A. annua .…”

Renoprotective Effects of Gallic Acid Against Gentamicin Nephrotoxicity Through Amelioration of Oxidative Stress in Rats

“…Moreover, other observations indicated that GA could mitigate LPO and GSH levels in RIR and NaF nephrotoxicity [41]. NO is a potent vasodilator that physiologically regulates the vascular system and renal tubular function [19,58]. Increased NO level plays the primary role in tissue damage through the reaction with superoxide anion and the production of peroxynitrite as a powerful oxidant.…”