DOI: https://doi.org/10.53350/pjmhs22163542 ORIGINAL ARTICLE 542 P J M H S Vol. 16, No. 03, MAR 2022 Nephro Defensive Efficiency of Cichorium Intybus Against Toxicity Caused by Copper Oxide Nanoparticles FIDAN FIKRAT AHMED 1 , OZDAN AKRAM GHAREEB 2 , AYOUB ALI HUSSEIN AL-BAYTI 3 1,3 Department of Medical Laboratory, College of Health and Medical Techniques Kirkuk, Northern Technical University, Iraq 2 Department of Community Health Techniques, Kirkuk Technical Institute, Northern Technical University, Iraq. Correspondence to: Fidan Fikrat Ahmed, Email: Fidanfikrat1972@ntu.edu.iq, ORCiD ID: https://orcid.org/0000-0002-3122-5347 ABSTRACT The penetration of nanotechnology into the medical world is constantly growing, and this raises concerns about its toxicity. This study aimed to illustrate the defense ability of Cichorium intybus (CI) against the nephrotoxicity induced by copper oxide nanoparticles (CuONPs) in a rat model. 32 laboratory rats were evenly distributed into 4 groups, each containing 8 animals. CON rats did not receive any dosage, whereas, CuONPs animals were dosed with copper oxide nanoparticles. As for the CuONPs + CI group, intoxicated rats were dosed with Cichorium intybus extract. Lastly, CI rats were given C.intybus extract only. The parameters of renal function, oxidative stress, and renal histological changes were measured. Animals treated with CuONPs showed negative changes in all examined parameters of kidneys compared to the CON group. However, co- administration of plant extract with NPs showed a clear improvement effect of these toxic changes. We concluded that the high dose of CuONPs causes significant kidney damage, and CI extract has a defensive effect against this toxicity. Keywords: Nephrotoxicity, nanoparticles, oxidative stress, histological changes. INTRODUCTION Nanomedicine has undergone rapid development in the twenty-first century [1,2], due to its great role in many delicate medical branches, especially related to cancers [3,4]. The strong adsorption capacity of nanoparticles has greatly enhanced their performance and applications [5]. Copper oxide nanoparticles (CuONPs) have acquired further attentiveness due to their distinct advantages compared to the rest of the metal oxides [6]. CuONPs have shown unique antioxidant, anticancer and antibacterial actions making them a portentous appliance for medical implementations [7,8]. In line with the increasing uses of nanoparticles, concerns have increased about the potential negative effects of their toxicity [9,10]. Several previous studies mentioned that nanoparticles may aggregate in different organ tissues of animal models, in particular the kidneys, causing adverse effects depending on dose and duration of exposure [11,12]. Even today, many developing countries are tending to consume medicinal herbs for their likability by the body as well as their fewer side effects [13]. Cichorium intybus (CI) is a perennial plant belonging to the family Asteraceae, characterized by being hardy with few green leaves. It grows in the wild within the temperate climate zone, especially in Eurasia and North Africa [14]. All parts of it contain several chemical compounds such as amino acids, vitamins, minerals, polyphenols, tannins, flavonoids and others. Therefore, it is widely used in traditional medicine CI extracts possess several health-promoting benefits including anti-inflammatory, antioxidant, and detoxifying [15]. This experimental study was designed to evaluate the defensive role of CI extract upon copper nanoparticle- induced nephrotoxicity in a rat model. MATERIALS AND METHODS Nanoparticles and plant extract: Nano liquid copper oxide dispersion has been used with the following properties: particle size from 30 to 50 nm, purity of nanopowder 99%, brown-black color, dissolved in water, application of catalyst and sensing as well as antibacterial, industrial grade, HWNANO brand, place of origin: Jiangsu, China. Organic Chicory (Cichorium Intybus) roots dried capsules 100 % natural herbal supplement, GMO-free, VEGAN (USA) were used in this experiential study. Animals and design of study: We used thirty-two albino males, aged between 5-6 months, and their weights 190-235 gm, in the current experimental study. They were obtained from animal houses within Iraqi universities. They were placed inside cages designated for them in a room that was ideally prepared in terms of temperature, ventilation and lighting. Rats were conditioned for 7 days before conducting the experiment. They were distributed into four groups with equal numbers as shown in Table 1. Upon termination of the experiment, all animals were anesthetized and dissected. Then, blood was collected from all animals used in the experiment by puncturing the heart, and the serum needed for assess kidney function was obtained. In addition to acquisition kidney tissues to assess oxidative stress, as well as to perform histological microscopic examination. Table 1: Dosing of experimental groups. Groups Treatment dosages Cont Rats were not given any treatment. Cuonps Rats were dosed with copper oxide nanoparticles at 250 mg/kg, orally for 14 consecutive days [16]. Cuonps+ ci The rats received CUONPs, followed shortly afterwards by an extract of Cichorium intybus at 200 mg/kg also orally [17]. Ci Animals dosed only with Cichorium intybus extract. Kidney function tests: To evaluate the efficiency of renal function, the levels of creatinine (Cr), blood urea (BU), and uric acid (Ur) were measured by Rock's kits with an automatic biochemical analyzer. Oxidative stress in kidney tissue: The levels of both Malondialdehyde (MDA) and reduced glutathione (GSH) in kidney tissues were determined enzymatically by spectrophotometric method previously described [18]. Kidney histology: After fixing the kidney tissues with formaldehyde, they are dried using ethanol and then embedded in paraffin. Tissue samples were sectioned and stained with histologically specific hematoxylin and eosin (H&E). Using light microscope (OPTIKA B-380 Series, Italy) histological measurements were made after being captured by a high-speed color camera (OptikaView TCB5.0 Camera, Italy). Statistical data analysis: Graph Pad Prism version 9 was used to analyze the data statistically. Data were displayed as mean ± standard deviation. Using one-way ANOVA followed by Tukey's multiple post hoc test, analyzes of differences between groups were performed. The level of statistical significance was considered at p value < 0.05. RESULTS Serological biochemical results related to renal functional markers as presented in figure (1) demonstrated a significant increase in serum levels of Cr (0.71±0.06), BU (30.05± 1.08) and Ur levels (1.61±0.07) in rats exposed to CUONPs compared to control (0.44± 0.04; 19.15± 0.80; and 1.13± 0.07 respectively). Whereas rats dosed with CUONPs and CI assured a considerable decrease in the levels of these kidney function indicators (0.51±0.03; 24.87±0.91; and 1.33±0.06) compared to the CUONPs group. Also, there was no important variance between control and CI groups.