Protective Effects of a Polyphenolic Phytochemical Quercetin against Oxidative Dysfunctions in Rats

Background Quercetin hastraditionally been used in various oxidative and urinary tract dysfunctions. Thecurrent project is consequently set to evaluate the defensive efficacy ofQuercetin against potassium bromate (KBrO3) induced testiculartissue oxidative dysfunctions through biochemical, hormonal, and genotoxicmarkers. Methods To observe theprotective efficacy of Quercetin against urinogenital oxidative dysfunction inrats, thirty six albino male rats were divided into six groups. Protectiveefficacies of Quercetin were checked on reproductive hormonal levels,antioxidant enzyme activities, lipids peroxidation (LP), and DNA damages. Results Potassium bromate exposure in experimentalanimals caused a reduction in the activities of antioxidant enzymes and disturbedhormonal secretions while enhancing the peroxidation of lipids andfragmentations of DNA. Cotreatment of Quercetin considerably (P<0.01)reversed these abnormalities with admiration to levels of hormones, antioxidantenzymes activities, and peroxidations of lipids secure to those seen inuntreated rats. (P < 0.01) Conclusion The findings of the current project revealedthat various doses of Quercetin are able to keep the testicular organ fromabnormal free radical dysfunctions. These improvements might be due to theantioxidant ability of polyphenolic bioactive constituent, i.e., Quercetin.


Introduction
Oxidative stress and dysfunction inside the cell take place as soon as the meditation of reactive oxygen species productionexceeds the system's antioxidant capability. In the aging process, oxidativestress plays an important role, and many pathogeneses are responsible fordiseases such as diabetes, cancer, neurodegenerative diseases, and respiratorydiseases [1]. 3 Various toxic reports revealed that KBrO3an oxidizing agent causes hepatotoxicity, and mesothelioma tumor development ininvestigational animals causes thyroid, kidney failure, andneurotoxicity [2]. 3 Various toxic reports revealed that KBrO3, an oxidizing agent, causes hepatotoxicity and mesothelioma tumor development ininvestigational animals, as well as causes thyroid, kidney failure, andneurotoxicity [3]. Experimental models have been the subject ofnumerous studies on oxidative injury and KBrO3-investigatingpossible mechanisms of induced carcinogenicity 3 [4]. Te KBrO3 produced reactive speciescombined with polyunsaturated fatty acids (PUFA) present in the tissue membraneto form DNA fragments [5] and decrease the activities of antioxidantenzymes and nonenzymatic antioxidants [6]. To prevent pathology, it is necessary tosupply external antioxidant compounds and maintain a balance between oxidantsand antioxidants. However, conventional and synthetic drugs used to treat oxidativestress are sometimes inadequate and can have many side efects [7]. However, most consumers prefer to use natural,more efective antioxidants for a safer approach. Accordingly, plant extractsand their metabolites such as favonoids, terpenoids, and phenolic components,provide an opportunity in this regard [8]. Te use of natural antioxidants to combat tissuedamage has been suggested as a healing agent as well as a coagent of medicine.Quercetin is used in the treatment of diferent types of cancer [9,10], infammation [11], oxidative damage [12], and antitumor efects [13]. Terefore, we designed to explore the protectingrole of Quercetin against potassium-bromated induced testicular carcinogenesisin rats.

Experimental Method.
Te present project is composed of thirty albinomale rats were divided into 06 groups, each group containing 06 rats: Group I as a control group. Group II wasgiven a 3 ml/kg DMSO dose. Group III wasgiven high grade 20 mg/kg KBrO3. 3 Group IV wascoadministered 75 mg/kg quercetin after 48 hrs of KBrO3 treatment. 3 Group V wascotreated with 150 mg/kg bw quercetin after 48 hrs of KBrO3treatment. 3 Group VI wasgiven 150 mg/kg quercetin alone. 2 For four weekstreatments were given twice a week. Upon the end of the experiment, all animalswere kept on a normal diet for 24 hrs without any treatment. Te animals wereanesthetized, and blood was isolated from the ventral side and collected into afalcon tube, centrifuged, and refrigerated. Ten the testicular tissue was removed anddried with blotting papers and weighed. After tissue coagulation, it wasdivided into 2 parts. For histology, one portion was cut and frozen anotherpart at -70°C after treatment with liquid N2 for further molecular andbiochemical studies.

Serum Biochemistry.
Variousparameters of serum including endocrine hormones such as testosterone,estradiol, luteinizing hormones (LH), and follicle-stimulating hormones (FSH)and prolactin were calculated using a kit purchased from 10227-Czech Republic(IM1447-IM3286) IMMUNOTECH Company for serum levels.

Genotoxicity Assays.
Quantitative DNA damages were estimated usingthe protocol of Lee and Jeong [24].

Histopathological
Studies. Cellular changeswere observed under a light microscope at 40x.

Statistical Analysis.
To determinetreatment efects, the variables were analyzed unilaterally using SPSS13.0, a wellknown computer software. Tesignifcance levels in diferent treatments were determined by LSD at 0.05% and0.01% probability levels.

Efects of Quercetin on Reproductive Hormonal Secretions.
Hypothalamuses, the pituitary axis (HPA axis) ofhormonal secretion were highly afected by ROS. Te efect of diferent dosesof Quercetin on serum levels of endocrine hormones such as testosterone,estradiol, luteinizing hormones (LH), and follicle-stimulating hormones (FSH)and prolactin were shown in Figure 1. Potassium bromated increased (P < 0.01)hormonal secretions of FSH, prolactin, andestradiol comparatively normal control group. Subsequent treatment withdiferent doses of Quercetin signifcantly eliminated the toxic efects of(P < 0.01) KBrO 3 KBrO3 and improved near-control serumlevels of prolactin and estradiol. Serum levels of FSH, testosterone, and LHwere signifcantly increased (P < 0.05, P > 0.01) at 75 mg/kg and 150 mg/kg by treatment ofQuercetin. Administration ofQuercetinwas more potential as it signifcantly restored the serum levels of luteinizinghormones and follicle stimulating hormones with 75 mg/kg and 150 mg/kgtreatment in the control group (P < 0.01).

Efects of Quercetin on Tissue Homogenate
Protein, SOD, POD, and CAT Activity. Administrations of Quercetin in diferent doseson tissue proteins and antioxidant enzymes such as POD, SOD, and CAT efects wereshown in Figure 2. Te concentrations of soluble tissue protein andthe activity of SOD, POD, and CAT were signifcantly reduced by the treatment ofpotassium bromated. Coadministration of various doses of Quercetin recoveredthese abnormalities and maintained (P < 0.01) near the control group (P < 0.01).

Efects of Quercetin on QR, c-GT, GSH-Px, GST, and GSR
Activity. Te protective efects of diferent doses of quercetin against KBrO 3 at diferent enzyme activities such as QR, c-GT, GSH-PX, GST, and GSR are shown in Figure 3. In rats, 20 mg/kg BW of KBrO 3 signifcantly (P < 0.01) reduces the activity of phase-II metabolic enzymes such as GST, GSR, and GSH-Px and increases (P < 0.01) the activities of c-GT and QR. After treatment with diferent doses of quercetin, enzyme activity was signifcantly restored near the control group (P < 0.01).    Table 1.

Discussions
Medicinal plants play an important role in thedetoxifcation of free radicals due to the presence of bioactive ingredients.In the present study, it was reported that various doses of Quercetin havesignifcantly reversed the KBrO 3induced pancreatic stress. Induction of KBrO 3 generated free radicals that caused the productionof highly reactive trichloroethylene and peroxy radical by the system ofcytochrome P 450 oxygenase trigger the initiation of lipidperoxidation [24]. Lipid peroxidation further causes strandbreakage and DNA mutation [24]. In the present study, KBrO 3 caused DNA damages in the testis, which weresignifcantly improved by various doses of Quercetin. Related to thesefndings, other reports revealed that plant extract and its various componentscomprehensively improved injuries caused by KBrO 3 intoxication and DNA strand breakage [1]. Free radicals are thought to cause cellularinjuries through lipid peroxidation [25]. In the current study, coadministration ofvarious doses of Quercetin considerably reversed the serum markers such asinsulin, lipase, and amylase as well as blood glucose levels. Our results werein agreement with other fndings [26], which reported that the same efect may be due to antioxidant activity. SOD, POD, and CAT are highly efectiveantioxidant enzymes responsible for the catalytic distribution of highlyreactive toxic radicals viz; superoxide and peroxide radicals [27][28][29]. In the present study, induction of KBrO 3 caused depletion of this enzymatic level whichwas signifcantly modulated by various doses of Quercetin. Te glutathionesystem includes GSH, GSH-px and GSH, hydrogen peroxide, and hydroperoxide causesdefciency [30][31][32]. In the present study, various doses of Quercetinsignifcantly reversed the reduction in the enzymatic level of GST, GR, GPx, andquinone reductase, which were depleted by induction of KBrO 3 . Similar observations were reported during theadministration of the chemical stimulant Coriandrum sativum, against oxidative stress [33,34].
Lipid peroxidation (LPO) is an automated processand can result in peroxidative tissue damage infammation, cancer, and aging asa common result of cell death [35,36]. In the present study, administration of KBRO 3    Evidence-Based Complementary and Alternative Medicine theLPO threshold by signifcantly reducing the MDA concentration, which is theefect of the extract against the lipid peroxidation of the tissue induced byKBrO 3 . Similar reports have been documented in various studies [37,38]. Te administration of KBrO 3 revealed abnormal cellular changes in testiculartissue. Coadministration of diferent doses of Quercetin showed protectiveefects and reduced cell degeneration. Our study revealed a similarinvestigation that agrees with previous fndings [39] while examining the protective efect of medicinal plants against KBrO 3 -induced toxicity in rats.

Conclusion
Te fnding of the current study showed thatvarious doses of Quercetin are strong antioxidant and is capable to protecttesticular damage from KBrO 3 -induced toxicity. However, further studies areneeded on the subject to study the mechanism of action.

Data Availability
All the data and material relevant to the paper are available in the paper.

Ethical Approval
Te study was conducted according to the protocol approved by the ethical committee of the university.

Conflicts of Interest
Te authors declare that there are no conficts of interest.