Europium Hydroxide Nanorods Mitigate Hind Limb Ischemia in Wistar Rats

Abstract

Lack of adequate blood supply to the limb extremities results in critical limb ischemia (CLI) and subsequent tissue death. Conventional approaches for CLI treatment include bypass surgery and angioplasty, which achieved limited clinical success due to their complex invasiveness. Of late, growth factor and cell‐based therapies emerged as alternative treatment strategies for CLI. However, these strategies could not achieve much success due to the associated drawbacks. Earlier, this study group develops europium hydroxide nanorods (EHN) which demonstrates potential proangiogenic (stimulating new blood vessel growth) properties. Recently it is shown that EHN could ameliorate the myocardial ischemia in Wistar rats by promoting therapeutic angiogenesis and mitigate cadmium‐induced vascular toxicity. Considering the importance of revascularization in managing CLI, it is hypothesized that the proangiogenic EHN might be useful for its effective treatment. Hence, in the present study, the therapeutic efficacy of EHN is comprehensively evaluated in the hind limb ischemia model of Wistar rats. The EHN‐administered ischemic rats exhibit improved motility, enhanced blood flow to the ischemic limb along with increased expression of angiogenic factors. Additionally, toxicity and pharmacokinetic studies of EHN in mice demonstrate their nontoxic nature, suggesting the feasibility of their practical clinical application for CLI treatment.

Smartly Engineered Casein Manganese Oxide Nanobiomaterials and Its Potential Therapeutic Angiogenesis Applications for Wound Healing and Limb Ischemia

“…Sighting Study (Single-Dose Study): The sighting study was performed for selecting appropriate dose for the main study along with determination of maximum tolerable dose (MTD). [27,107] The sighting study or singledose toxicity study was performed in female C57BL/6J mice (n = 2) by intraperitoneal administration (I.P.) of CMnNP.…”

“…Limb Ischemia: Unilateral hindlimb ischemic prototype was established in female mice (BALB/c) through femoral artery ligation as per published report. [27,51] For developing a model of hindlimb ischemia, initially the animals were anesthetized with I.P. administration of ketamine plus xylazine cocktail injection.…”

“…Blood Perfusion Rate: The blood perfusion rate (mean flux value) around wound area in C57BL/6J mice was determined using MOOR LDI2-HR laser Doppler imager, Moor Instruments, UK. [27,51] The LDI for all the wounded mice were taken at different time, namely, i) before making wound at day 0; ii) after making wound at day 0; iii) day 4; and iv) day 10. The blood perfusion rate was measured at the ROI near the specified wound area using laser Doppler imager software V6.1.…”

“…Angiogenesis also plays significant role in wound healing, bone formation, cardiovascular diseases, ischemic diseases, etc. [25][26][27][28][29] The above information encouraged us to explore the possibility of angiogenic properties of Mn in nanoform and its mechanistic pathways. Even though there are several reports available in literature about other inorganic nanoparticles regarding their angiogenic property and also of manganese oxide-based nanoparticle for anti-angiogenic applications, [30,31] but to the best of our knowledge there is not a single report of Mn and its nanoform that itself demonstrate the pro-angiogenic properties.…”

Effective treatment of intractable diseases using nanoparticles to interfere with vascular supply and angiogenic process

“…In conclusion, the current research presents a novel nanomedicine method utilizing ZONFs for PAD treatment. Recent research has demonstrated that nanorods made of europium hydroxide can promote therapeutic angiogenesis, which in turn helps reduce the vascular toxicity caused by cadmium exposure [ 188 ]. This effect is seen in Wistar rats who have had myocardial ischemia.…”