Rutin Attenuates Vancomycin-Induced Nephrotoxicity by Ameliorating Oxidative Stress, Apoptosis, and Inflammation in Rats

Abstract

Nephrotoxicity is the major limiting factor for the clinical use of vancomycin (VCM) for treatment of serious infections caused by multiresistant Gram-positive bacteria. This study investigated the renal protective activity of rutin in a rat model of VCM-induced kidney injury in male Wistar rats. VCM administered intraperitoneally at 200 mg/kg twice daily for 7 successive days resulted in significant elevation of blood urea nitrogen and creatinine, as well as urinary N-acetyl-β-D-glucosaminidase. Coadministration of VCM with oral rutin at 150 mg/kg significantly reduced these markers of kidney damage. Rutin also significantly attenuated VCM-induced oxidative stress, inflammatory cell infiltration, apoptosis, and decreased interleukin-1β and tumor necrosis factor alpha levels (all P < 0.05 or 0.01) in kidneys. Renal recovery from VCM injury was achieved by rutin through increases in Nrf2 and HO-1 and a decrease in NF-κB expression. Our results demonstrated a protective effect of rutin on VCM-induced kidney injury through suppression of oxidative stress, apoptosis, and downregulation of the inflammatory response. This study highlights a role for oral rutin as an effective intervention to ameliorate nephrotoxicity in patients undergoing VCM therapy.

Rutin‐protected BisGMA‐induced cytotoxicity, genotoxicity, and apoptosis in macrophages through the reduction of the mitochondrial apoptotic pathway and induction of antioxidant enzymes

“…42 Rutin ameliorates carbon tetrachloride or vancomycininduced kidney injury in mice models. 44,45 In the present study, levels of intracellular ROS could be reduced by rutin in BisGMA-treated macrophages. AOEs are capable of the deactivation and detoxification of ROS.…”

Vancomycin‐Induced Kidney Injury: Animal Models of Toxicodynamics, Mechanisms of Injury, Human Translation, and Potential Strategies for Prevention

“…These studies have been reviewed in detail 111 . Since then, spirulina and pycnogenol , 112 mitoTEMPO, naringenin, 113 a free radical scavenger zingerone, 114, 115 DHA‐enriched phosphatidylcholine (DHA‐PC), 116 rutin, 117 and silymarin 118 have been evaluated in animal studies. In our opinion, the antioxidants that are most ready for clinical trials include preparations that are already clinically available, such as atorvastatin, vitamin C, vitamin E, N‐acetylcysteine, erythropoietin, and erdosteine.…”

The Potential Modulatory Effect of Rutin on Titanium Dioxide Nanoparticles-Induced Renal Injury in Male Mice

“…This result suggested a possible role of rutin in diminishing the signal generated either via integral membrane death receptor proteins or via mitochondrial cytochrome c release pathway, and finally reducing the activation of effector caspase-3, thereby attenuating the apoptotic death and disruption concerning renal tubular cells induced by cisplatin [21]. In addition, rutin supplementation attenuated significantly vancomycin-induced renal apoptosis through decreasing the activity of caspase-3 and caspase-9 [39]. Moreover, Ma et al [36] reported that different doses of rutin supplementation decreased the release of cytochrome c and the activity of caspase-3 in kidneys of CCl4treated mouse.…”

“…NF-B is a necessary transcriptional mediator for production of the proinflammatory cytokines that plays a pivotal role in the injury of tubular epithelial cells through generating ROS [38]. Qu et al [39] established that a protecting effect of rutin on vancomycin-caused renal damage was through reducing the NF-B expression and TNF-α generation to the control levels. In addition, rutin alleviated cisplatininduced renal injury through its inhibitory effect on NF-B and TNF-α pathway mediated inflammation [21].…”