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IJCRR - 10(20), october, 2018

Pages: 25-31

Date of Publication: 26-Oct-2018


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Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice

Author: K. Krupashree, P. Rachitha, G. V. Jayashree, Farhath Khanum

Category: Life Sciences

Abstract:Objectives: The aim of the present study is to evaluate hepatoprotective effect of Picrorhizakurroaextracts (PKE) against Fumonisin b1 (Fb1) induced hepatotoxicity. Methods: Hepatoprotective analysis was done by estimating serum biochemical parameters Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), antioxidant enzyme status lipid peroxidations, ROS generation, and protein carbonyls were also estimated to know the oxidative damage. Further protein expressions were confirmed by western blotting. Results: The mice treated with 100 and 200 mg/kg b.wt PKE, showed a significant reduction in serum AST and ALT to 175.41 \? 7.82, 68.52\?1.57 and 126.64 \? 1.72, 57.41\?1.28 units/ml of serum respectively. The decrease in antioxidant levels with Fb1 was significantly restored with 100 and 200 mg/kg by wt PKE. The lipid peroxidation products with Fb1 treatment was also reduced with PKE supplementation. The Fb1 induced ROS was reduced with 60 and 140% by 100 and 200 mg/kg/ by wt PKE administration. The PKE restored CAT and GPx enzyme/protein levels and further down regulated caspase 8 and caspase 3 expression. Conclusion: The present observations suggested that the treatment with PKE extract enhance the recovery from Fb1 induced hepatic damage due to its antioxidant and hepatoprotective property.

Keywords: Fumonisin b1, Picrorhizakurroa, Antioxidants, Oxidative stress, Apoptosis

Full Text:

Introduction

Fumonisins are group of mycotoxins mainly produced from Fusariumverticillioides, Fusariummoniliforme is a common contaminants of corn and corn products throughout the world. The most potent and abundant of the class of fumonisins is fumonisin b1 (Fb1) which causes specific toxicological effects in humans and animals [1,2]. Fumonisin b1 causes equine leukoencephalomalacia in horse and porcine pulmonary edema in swine  [3,4], and it has been reported as hepatotoxic, nephrotoxic, and carcinogenic in animals and human [5]. In vivo studies demonstrated that fumonisin b1 also induced apoptosis and oxidative stress in kidney and liver [6,7].

Fb1 are known to affect sphingolipid metabolism by inhibiting the enzyme ceramide synthase. Inhibition of ceramide synthase causes apoptosis, accumulation of sphingoid bases (sphinganine and sphingosine) and decreases the ceramide [8,9]. Fb1 has been shown to disrupt lipid biosynthesis in vitro and in vivo in rat liver with changes occurring in the major cellular membrane phospholipids fractions and their fatty acid (FA) content by inducing the oxidative radicals such as superoxide anion and nitric oxide which are responsible for oxidative stress in the tissue [10]. Hence Fb1 is more toxic and abundant fumonisins causes liver damage in many animals [11].

PicrorhizakurroaRoyle ex Benth (P.kurroa) commonly called kutki a well-known Ayurvedic herb. Generally it has been used to treat liver toxicity and upper respiratory tract, and also to treat dyspepsia, scorpion sting and chronic diarrhea [12,13,14]. The P.kurroa contains chemical constituents like Apocynin, picrorhizoside, picroside-I, cinnamic acid, verminosidepicrogentioside, piscrocin, cucurbitacin, pikuroside, vanillic acid, picrosecoside –I [12,15,16].

P. kurroa has many medicinal benefits such as anti-allergic, anti-neoplastic immunomodulatory and anti-anaphylactic activities [12,17,18] The P.kurroa has been recently reported to inhibit arthritis through inhibition of pro-inflammatory cytokines and angiogenesis and which have protective effects against 2-acetylaminofluorene-induced hepatotoxicity in Wistar rats and non alcoholic fatty liver disease [19,20,21]. The active component Picroliv against Leishmaniadonovani infections in Mesocricetusauratus and hepatoprotective compound in mice [22,23,24]. The flavonoid apocynin is one of the active component of P. kurroa and has been noted to attenuate Parkinson's, ischemia-reperfusion and hypoxia by arresting NADH oxidase expression during oxidative stress.[12,25,26,27]. Hence the present study is to investigate the P. kurroa protective effects against Fb1 induced hepatotoxicity.

Materials and methods

Chemicals and reagents

Fumonisin b1, 2, 7-dichloro-dihydrofluorescein diacetate (Sigma Bangalore), 2-nitrobenzoicacid (DTNB) Hi-Media (Bangalore, India). The other chemicals used were of high purity grade and were procured from Merck (Bangalore, India).

 Plant material

P. kurroa root material was purchased from the local market and identified by Dr. K. Madhava Chetty, Botanist, Department of Botany, Sri Venkateswara University, Tirupati, India. A voucher specimen (Herbarium Accession Number 801) was deposited in the herbarium, Department of Botany, S.V. University, Tirupati, India.

Preparation of 70 % ethanolic fraction of P.kurroa(PKE)

P. kurroa roots were washed thoroughly, shade dried and finely powdered. The 100g root powder was macerated with 70% ethanol in a shaker for 2 days. The extract was filtered using micropore membrane and concentrated using flash evaporator followed by lyophilization to remove the residual water. The yield of the extract was recorded as 25g.

Experimental design

Forty eight male Balb/c mice weighing 25g were selected from the stock colony, Defence Food Research Laboratory, Mysore, India. The animals were housed in acrylic fibre cages, temperature (25 ± 20C) and maintained in 12 h light/dark cycle. The mice were fed with a commercial pellet diet (Sri Venkateswara Enterprises, Bangalore, India) and water was provided ad libitum. The animal studies were conducted according to the guidelines from institute animal ethical committee for the purpose of the control and supervision of experiments on animals NO: 28/IAEC/CPCSEA. (I) Control group (II) PKE 200 mg/kg b/wt (body weight)   (III) Fb1 2.25mg/kg b/wt (IV) Fb1 2.25mg/kg b/wt + PKE 50mg/kg b/wt (V) Fb1 2.25mg/kg b/wt + PKE 100mg/kg b/wt (VI) Fb1 2.25mg/kg b/wt + PKE 200mg/kg b/wt. PKE was pretreated for 7 days oral administration. Fb1 2.25mg/kg b/wt was injected subcutaneously for 3 days. Controls mice were fed orally with an equal amount of saline. After the experiment mice were sacrificed, serum and liver tissues were collected for analysis. Bhandari et al., 2001 [28].

Serum biochemistry

Estimation of ALT and AST

 The serum biochemical markers such as ALT and AST were determined according to the kit suppliers protocols (Cat no. 11409003 and 11408002 Canada).

Tissue biochemical parameters

Estimation of hepatic antioxidant enzymes

Liver tissues were homogenized in 50mM phosphate buffer saline (pH 7.4). The hepatic antioxidant enzymes such as SOD, GPx and GR were determined according to the protocols of kit supplier (Randox, Cat no. SD. 125, RS 504 and GR 2368, Canada). DTNB method was used to determine Glutathione content [29]. CAT enzyme content was estimated manually by spectrophotometric method [30]and the results were expressed in U/g tissue. Protein contents were determined by Bradford method (1976) [31] and the results were expressed as U/mg of protein.

Estimation of hepatic lipid peroxidation

Hepatic lipid peroxidation was determined by measuring the malondialdehyde according to Buege and Aust (1978) [32]. Liver tissues were homogenized in 2mL of phosphate buffer (pH 7.0). TCA (10%), 0.5mL and 2mL of TBA mixture were added to tissue homogenate (0.5mL). The TBA mixture contained TBA (0.35%), SDS (0.2%), FeCl3 (0.05mM) and BHT in glycine-HCl buffer (100mM, pH 3.6). The above reaction mixture was boiled at 1000C for 30 min. The mixture was centrifuged at 8000 rpm (Revolutions per minute) for 10min and the absorbance was measured at 532 nm and the results were expressed as moles/mg of protein.

Estimation of ROS

Fluorescent probe 2’, 7’- dichloro-dihydrofluoresceindiacetate was used to detect ROS generation in liver tissue by Wang and Joseph (1999) [33] method. To the liver fractions 40 µl of 1.25 mM 2’, 7’- dichlorfluorescein-diacetate and 142 µl methanol was added and the samples were incubated for 15 min at 370C. The fluorescence was measured at 485 nm excitation and 525 nm emission using Hidex plate chameleon TM 144 V (Finland).

Western blot analysis

The oxidative and apoptosis marker expression was analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. The liver sample was homogenized with lysis buffer, pH 7.4 with protease inhibitor cocktail and total protein levels were estimated by the method of Bradford (1976) [31] The liver homogenate 50µg of proteins were separated on SDS-PAGE and transferred onto a nitrocellulose membrane using an electro blotting apparatus (Cleaver Scientific Ltd, UK). After transfer, the membranes were probed with primary antibodies against GAPDH (sc-5286) GPx (sc-22146), CAT (sc-34280), caspase 8 (sc-81657), caspase 3(sc-52746),(Santa Cruz Biotechnology, Santa Cruz, CA, USA, sigma) at 1:1,000 dilution and incubated at room temperature for 3 h. The membranes were then washed in TBST followed by incubation for 2 h at room temperature in dark with horseradish peroxidase (HRP) conjugated rabbit anti-goat, goat anti-mouse and goat anti-rabbit secondary antibodies (DAKO, Denmark) at 1:10,000 dilutions. The membranes were washed again and developed using a chemiluminescence detection system (ProteoQwest1, Sigma). Developed membranes were exposed to X-ray film and the developed band intensity was captured.  NIH image J software was used to measure the western blot band intensity.

Statistical analysis

The results were analyzed by one-way ANOVA followed by a Tukey’s HSD- post hoc test. Significance was set at 0.05 and all comparisons were made against the control group.

Results

P.kurroa regulates ALT and AST

The hepatic function marker namely alanine aminotransferase (ALT), aspartate aminotransferase (AST) were estimated to diagnose the liver health. These enzymes were elevated in toxic or stress conditions due to the extracellular release particularly in liver. In the present study observed an increase in ALT and AST (p < 0.05) (Table. 1). However P. kurroa supplemented mice showed a dose dependent decrease in ALT and AST contents (p < 0.05) which indicates its protective effects against liver damage.

Protective effect of P. kurroa against oxidative stress

Antioxidant enzymes namely CAT, GPx, GR and GSH gets decreased when the liver undergo toxic condition induced by Fb1. In the present study observed decrease in antioxidant enzyme content in Fb1 challenged mice (p< 0.05). However a significant increase (p< 0.05) in antioxidant enzymes was observed with 100 and 200 mg/kg by wt P. kurroa supplementation. Whereas SOD was not affected by Fb1 treatment. (Table 2).

P. kurroa inhibits lipid peroxidation

Oxidative degradation of lipids caused by free radicals was measured by estimating malondialdehye content. The Fb1 treated liver showed the increase of malondialdehyde formation (P< 0.05), whereas P. kurroa supplemented mice decreased lipid peroxidation with 100 and 200mg/kg by wt PKE treatment (P< 0.05) which suggests that P. kurroa exerts protective effects against free radicals mediated lipid damage (Table 2).

P. kurroa inhibits ROS generation

The reactive oxygen species such as hydroxyl radical (HO), superoxide anion (O2), and hydroxyl anion (HO) trigger the cellular damage by oxidizing the biomolecules therefore estimation of ROS is essential to study the oxidative stress. The ROS estimation was carried out using fluorescent probe DCFH2DA. Here we observed 264% increases (p < 0.05) in fluorescence in Fb1 treated liver homogenates. The pre-treatment of PKE decreased 92 to 165% (p < 0.05) of ROS generation respectively (Fig. 1(A)).

Protective effects of P. kurroa on oxidative stress and apoptotic biomarker

The effect of P. kurroa against Fb1 stress was further evaluated by western blotting. The key enzymes of oxidative stress such as GPx, CAT and GAPDH and apoptotic enzymes caspase 3 and caspase 8 was evaluated (Fig. 3). The antioxidant biomarkers GPx and CAT were down-regulated with Fb1 treatment and caspase 8, caspase 3 were increased in the expression. Whereas P.kurroa pretreatment significantly restored the GPx, CAT expression and down regulated the apoptotic enzymes caspase3, caspase 8 protein expression.

Discussion

Fumonisin b1 are secondary metabolites of fungi which are associated with many disorders in animals and humans and also responsible for apoptosis and oxidative stress. Protective effect of herbal extracts against fumonisin b1 induced toxicity has fewer reports. El-Adawi et al. (2011) [34] studied protective effects of milk thistle and grape seed extracts on fumonisin B1 induced hepato- and nephro-toxicity in rats and Sozmen et al. (2014) [35] reported protective effects of sylimarin against fumonisin B1-induced hepatotoxicity in mice.P. kurroa is a well-known ayurvedic herb and shown hepatoprotective activity in diverse models of liver toxicity. Hence the present study investigated the hepatoprotective effects induced by fumonisin b1 induced toxicity.

AST and ALT are enzymes that catalyze the transfer of α-amino groups from aspartate and alanine to the α-keto group of ketoglutaric acid to generate oxalacetic and pyruvic acids respectively when the liver is in toxic or stress condition, therefore serum concentrations of aminotransferases level increase. Several reports show that plants and phytochemicals attenuate the aminotransferases level [36]. The pretreatment of animals with the extracts P.kurroa resulted to a significant and dose dependent decrease in the levels of ALT and AST.

Enzymes such as superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione (GSH) have been proposed as biomarkers of oxidative stress and toxic effect of tissue. CAT is well known antioxidant enzyme which detoxifies the hydrogen peroxide without electron donor and GPx also metabolize H2O2 to non-toxic products [37]. The GSH plays a fundamental role in cellular metabolism which provides the defence against reactive oxygen species and other toxic radicals and the GR is responsible for generation of GSH. In the present study we observed a decrease concentration of these antioxidant enzymes and the pretreatment of  P. kurroa showed a recovery in the activity of these enzymes several reports also demonstrated that supplementation of herbal extracts can increases that antioxidant level induced by other toxic radicals.

The lipid peroxidation involves the mechanism formation or propagation of lipid radicals by up taking the oxygen and rearrangement of the double bonds in unsaturated lipids and the eventual destruction of membrane lipids and final products breaks downs including ketones, alkanes, aldehydes and ethers [38]. This lipid peroxidation was measured by malondialdehyde in the present study the malondialdehyde level was increased in the Fb1 treated group and it was minimized by P. kurroa pretreated group.

Western blot is used to separate and identify proteins separated based on molecular weight. The house keeping gene glyceraldehyde 3-phosphate dehydrogenase (GAPDH) used as reference proteins to normalize the target protein during the protein targeting. Therefore, to accurately compare western blotting signals, one must compensate for these non-sample-related variations in signal intensity so GAPDH increasing expression shows that the house keeping proteins are subject to change in many biological conditions, such as toxic condition and some diseases [39].

The antioxidant marker proteins CAT and GPx already demonstrated that in biochemical parameters the enzyme activity decreased in oxidative stress condition. In the western blotting also the expression of GPx and CAT down regulated with Fb1 whereas pretreatment of P. kurroa significantly restored the enzyme. Increasing the antioxidant able to accelerate the removal of the reactive oxygen species so which may the reason for increasing the GPx, CAT in the present study.

Fb1 treatment activates enzyme Caspase-8, Caspase-8 is signalling molecule involved in TNF tumor necrosis factor-alpha apoptotic pathway plays a pivotal role in Fb1-induced apoptosis [26]. In the present study we observed up regulation of Caspase-8 and Caspase-3 whereas P. kurroa pretreated with 200mg down regulates the expression of apoptotic enzymes. P. kurroa seems to be a promising herb to protect Fb1 induced hepatotoxicity. The extract was found to prevent lipid oxidation and also to increase the activity of the antioxidant enzymes apart from down regulating the caspases. Hence with the protein expression studies P. kurroa showed the protective effect against Fb1 induced hepatotoxicity.

Conclusion

Fb1 associated with hepatotoxic effect and induction of oxidative stress. Modulating roles against ROS mediated damage for cell survival by nutrition supplement is therefore of interest. Present study evaluated the modulating properties of P. kurroa against oxidative stress and apoptosis mediated by Fb1. There inhibitory effects might be due to enriched active ingredients present in P. kurroa. Further molecular and analytical studies are necessary to understand the concealed mechanism of action of the P. kurroa extract and also for the usage as therapeutic agent.

Acknowledgement

Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.

Conflict of interest: None

Source of funding: None

Fig. 1 Effect of PKE on hepatic ROS generation. Mice were treated with different doses of PKE followed by Fb1 and the liver ROS generation was measured using spectrofluorimeter (n= 8, P < 0.05, significantly different from the control group and homogenous sub groups share common letter (a= P< 0.05 versus Fb1 treated group and b= P< 0.05 versus control group)).

Fig.2. The protective effect of pre-treatment of PKE on Fb1 induced expression of oxidative stress marker proteins CAT, GPx and apoptosis marker proteins caspases-8, caspase-3 analysed by western blotting (B,C,D,E). The band intensity is calculated by Image-J software. The data are represented as mean ± SD of three independent experiments. #P<0.05 versus control group, *P<0.05 versus Fb1 treated group.

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A study by Dorothy Ebere Adimora et al. entitled \"Remediation for Effects of Domestic Violence on Psychological well-being, Depression and Suicide among Women During COVID-19 Pandemic: A Cross-cultural Study of Nigeria and Spain\" is awarded Best Article of Vol 14 issue 23
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A Study by Monica K. entitled "Risk Predictors for Lymphoma Development in Sjogren Syndrome - A Systematic Review" is awarded Best Article for Vol 14 issue 13
A Study by Mokhtar M Sh et al. entitled "Prevalence of Hospital Mortality of Critically Ill Elderly Patients" is awarded Best Article for Vol 14 issue 12
A Study by Vidya S. Bhat et al. entitled "Effect of an Indigenous Cleanser on the Microbial Biofilm on Acrylic Denture Base - A Pilot Study" is awarded Best Article for Vol 14 issue 11
A Study by Pandya S. et al. entitled "Acute and 28-Day Repeated Dose Subacute Toxicological Evaluation of Coroprotect Tablet in Rodents" is awarded Best Article for Vol 14 issue 10
A Study by Muhammad Zaki et al. entitled "Effect of Hemoglobin Level on the Severity of Acute Bronchiolitis in Children: A Case-Control Study" is awarded Best Article for Vol 14 issue 09
A Study by Vinita S & Ayushi S entitled "Role of Colour Doppler and Transvaginal Sonography for diagnosis of endometrial pathology in women presenting with Abnormal Uterine Bleeding" is awarded Best Article for Vol 14 issue 08
A Study by Prabhu A et al. entitled "Awareness of Common Eye Conditions among the ASHA (Accredited Social Health Activist) Workers in the Rural Communities of Udupi District- A Pilot Study" is awarded Best Article for Vol 14 issue 07
A Study by Divya MP et al. entitled "Non-Echoplanar Diffusion-Weighted Imaging and 3D Fiesta Magnetic Resonance Imaging Sequences with High Resolution Computed Tomography Temporal Bone in Assessment and Predicting the Outcome of Chronic Suppurative Otitis Media with Cholesteatoma" is awarded Best Article for Vol 14 issue 06
A Study by Zahoor Illahi Soomro et al. entitled "Functional Outcomes of Fracture Distal Radius after Fixation with Two Different Plates: A Retrospective Comparative Study" is awarded Best Article for Vol 14 issue 05
A Study by Ajai KG & Athira KN entitled "Patients’ Gratification Towards Service Delivery Among Government Hospitals with Particular Orientation Towards Primary Health Centres" is awarded Best Article for Vol 14 issue 04
A Study by Mbungu Mulaila AP et al. entitled "Ovarian Pregnancy in Kindu City, D.R. Congo - A Case Report" is awarded Best Article for Vol 14 issue 03
A Study by Maryam MJ et al. entitled "Evaluation Serum Chemerin and Visfatin Levels with Rheumatoid Arthritis: Possible Diagnostic Biomarkers" is awarded Best Article for Vol 14 issue 02
A Study by Shanthan KR et al. entitled "Comparison of Ultrasound Guided Versus Nerve Stimulator Guided Technique of Supraclavicular Brachial Plexus Block in Patients Undergoing Upper Limb Surgeries" is awarded Best Article for Vol 14 issue 01
A Study by Amol Sanap et al. entitled "The Outcome of Coxofemoral Bypass Using Cemented Bipolar Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fracture of Femur in a Rural Setup" is awarded Best Article Award of Vol 13 issue 24
A Study by Manoj KP et al. entitled "A Randomized Comparative Clinical Trial to Know the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block Against Multimodal Analgesia for Postoperative Analgesia Following Caesarean Section" is awarded Best Article Award of Vol 13 issue 23
A Study by Karimova II et al. entitled "Changes in the Activity of Intestinal Carbohydrases in Alloxan-Induced Diabetic Rats and Their Correction with Prenalon" is awarded Best Article of Vol 13 issue 22
A Study by Ashish B Roge et al. entitled "Development, Validation of RP-HPLC Method and GC MS Analysis of Desloratadine HCL and It’s Degradation Products" is awarded Best Article of Vol 13 issue 21
A Study by Isha Gaurav et al. entitled "Association of ABO Blood Group with Oral Cancer and Precancer – A Case-control Study" is awarded Best Article for Vol 13 issue 20
A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19
A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


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International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

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