A study on assessing the toxic effects of ethyl paraben on rohu (Labeo rohita) using different biomarkers; hemato-biochemical assays, histology, oxidant and antioxidant activity and genotoxicity.

Parabens are being used as preservatives due to their antifungal and antimicrobial effects. They are emerging as aquatic pollutants due to their excessive use in many products. The purpose of this study was to determine the toxic effect of ethyl paraben (C9H10O3) on the hematobiochemical, histological, oxidative, and anti-oxidant enzymatic and non-enzymatic activity; the study also evaluates the potential of ethyl paraben to cause genotoxicity in Rohu Labeo rohita. A number of 15 fish with an average weight of 35.45±1.34g were placed in each group and exposed to ethyl paraben for 21 days. Three different concentrations of ethyl paraben, i.e., T1 (2000µg/L), T2 (4000 µg/L), andT3 (6000 µg/L) on which fish were exposed as compared to the control T0 (0.00 µg/L). Blood was used for hematobiochemical and comet assay. Gills, kidneys, and liver were removed for histological alterations. The results showed a significant rise in all hemato-biochemical parameters such as RBCs, WBCs, PLT count, blood sugar, albumin, globulin, and cholesterol. An increase in aspartate aminotransferase (AST) and alanine transaminase (ALT) levels directed the hepatocytic damage. Histological alterations in the liver, gills and kidneys of fish were found. Ethylparaben induces oxidative stress by suppressing antioxidant enzyme activity such as SOD, GSH, CAT and POD. Based on the comet assay, DNA damage was also observed in blood cells, resulting in genotoxicity. Findings from the present study indicate that ethyl paraben induces hemato-biochemical alterations, tissue damage, oxidative stress, and genotoxicity.

Emerging role of lipophagy in liver disorders.

Lipophagy is a selective degradation of lipids by a lysosomal-mediated pathway, and dysregulation of lipophagy is linked with the pathological hallmark of many liver diseases. Downregulation of lipophagy in liver cells results in abnormal accumulation of LDs (Lipid droplets) in hepatocytes which is a characteristic feature of several liver pathologies such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Contrarily, upregulation of lipophagy in activated hepatic stellate cells (HSCs) is associated with hepatic fibrosis and cirrhosis. Lipid metabolism reprogramming in violent cancer cells contributes to the progression of liver cancer. In this review, we have summarized the recent studies focusing on various components of the lipophagic machinery that can be modulated for their potential role as therapeutic agents against a wide range of liver diseases.

Diagnostic and therapeutic value of EVs in lungs diseases and inflammation.

Extracellular vesicles (EVs) are membrane-derived messengers which have been playing an important role in the inflammation and pathogenesis of lung diseases. EVs contain varieties of DNA, RNA, and membrane receptors through which they work as a delivery system for bioactive molecules as well as intracellular communicators. EV signaling mediates tumor progression and metastasis. EVs are linked with many diseases and perform a diagnostic role in lung injury and inflammation so are used to diagnose the severity of diseases. EVs containing a variety of biomolecules communicate with the recipient cells during pathophysiological mechanisms thereby acquiring the attention of clinicians toward the diagnostic and therapeutic potential of EVs in different lung diseases. In this review, we summarize the role of EVs in inflammation with an emphasis on their potential as a novel candidate in the diagnostics and therapeutics of chronic obstructive pulmonary disease, asthma, and sarcoidosis.

Effect of heterologous platelet-rich plasma on liver and modulation of glucose metabolism and Wnt signalling pathways in diabetic mice.

BACKGROUND: The current study was designed to highlight the effects of heterologous platelet-rich plasma (PRP) on deteriorated hepatic tissues and impaired glucose metabolism of alloxan-induced diabetic mice. METHODS: 30 male mice were divided into a control (CG), PRP (PG), diabetic (DG), and two treated groups (T1G and T2G). PG was given PRP treatment (0.5 ml/kg body weight) twice a week for four weeks. DG, T1G and T2G were given alloxan (150 mg/kg) to induce diabetes. After confirmation, PRP treatment was given to T1G and T2G for two and four weeks respectively while DG was left untreated. Upon completion of the said experimental period, liver samples were taken for histological and gene expression analyses. RESULTS: The study found that the liver tissue of the DG group showed signs of damage, including hepatocyte ballooning, sinusoid dilatation, and collagen deposition. However, these changes were significantly reduced in both T1G and T2G groups. The expression of several genes related to liver function was also affected, with upregulation of Fbp1 and Pklr, and downregulation of Pck1 in the DG group. PRP treatment restored Fbp1 expression and also increased the expression of glycolytic pathway genes Hk1 and Gck, as well as Wnt signalling pathway genes Wnt2, Wnt4, and Wnt9a in both treated groups. CONCLUSION: Current study revealed that heterologous PRP may partly alleviate high glucose levels in diabetics possibly by mediating glucose metabolism via inhibition of Wnt signalling pathway.

Bisphenol S induced dysregulations in liver; iron regulatory genes and inflammatory mediators in male Wistar rats.

Bisphenol S (BPS), an analog of bisphenol A (BPA), has been frequently detected in consumer products, food wrappers, plastics, and thermal papers. Since the liver is a hub of metabolic and detoxification pathways, thus intimately related to BPS presence in the environment and body. The current study was designed to investigate the effects of BPS administration in an animal model. Twenty-five male Wistar rats weighing 175 ± 25 g were randomly divided into control and treated groups. The control group was further divided into group I (no treatment) and group II (corn oil), whereas the treatment group was divided into D-I (40 mg/kg/day), D-II (200 mg/kg/day), and D-III (400 mg/kg/day) groups, getting oral doses of BPS for 15 days. Data analysis showed a significant statistical increase in hepatic enzymes ALT (33.4%), AST (25.4%), and ALP (529.6%) in the D-III group along with the development of hypercholesterolemia and hypertriglyceridemia in all BPS groups. Aberrant mRNA expressions of some key hepatic iron regulatory genes and inflammatory mediators were evident through qRT-PCR. Bisphenol S caused congestion of central vein from mild to moderate in hepatic sections. In conclusion, our investigation insinuates BPS intoxication potential and therefore may not be a safe alternative to BPA.

Diagnostic, prognostic and therapeutic potential of long noncoding RNAs in cancer.

Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides in length and undergo splicing, capping, polyadenylation, and editing just like mRNA. Evidence is growing that they regulate transcription, splicing, RNA degradation, and translation of genes and that their expression has been linked to a variety of illnesses, including cancer. The advancement of next-generation and high-throughput sequencing has changed the way lncRNAs are identified and characterized, revealing a relationship between lncRNAs and several tumor types. Since then, they have gained a significant attraction as a promising candidate in cancer diagnosis, prognosis, and therapy. Furthermore, they are a good candidate for consideration as tumor biomarkers due to their high stability, better tissue/cell selectivity, aberrant expression in certain malignancies, and easy and noninvasive detection. In addition, lncRNAs are being examined as therapeutic targets in clinical trials for a variety of malignancies. This review highlights the potential of lncRNAs as biomarkers or therapeutic targets in light of the current progress, clinical investigations, and patents filed so far.

High-fat diet intake ameliorates the expression of hedgehog signaling pathway in adult rat liver.

BACKGROUND: Disproportionate fatty diet intake provokes hepatic lipid accumulation that causes non-alcoholic fatty liver disease, triggering the embryonically conserved Hedgehog (Hh) pathway in the adult liver. The present study incorporates exploring the impact of chronically administered unsaturated (D-1) and saturated (D-2) fat-enriched diets on hematological parameters, liver functioning, and lipid profile in the rat model. Besides, hepatohistology and real time gene expression analysis of Hh signaling pathway genes i.e., Shh, Ihh, Hhip, Ptch1, Smo, Gli1, Gli2, and Gli3 were carried out. METHODS AND RESULTS: Fifteen Rattus norvegicus (♂) of 200 ± 25 g weight were grouped into control, D-1, and D-2. Animals were fed on their respective diets for 16 weeks. Fatty diet intake resulted in neutropenia, lymphocytosis, monocytosis, polycythemia, and macrocytosis in both experimental groups. Altered liver injury biomarkers, hypertriglyceridemia, and significantly increased very-low-density lipoprotein VLDL were also noted in both high-fat diet (HFD) groups as compared to control. Hepatohistological examination showed disrupted microarchitecture, infiltration of inflammatory cells, cellular necrosis, widened sinusoidal spaces, and microvesicular steatotic hepatocytes in D-1 and D-2. Collagen deposition in both HFD groups marks the extent of fibrosis. Significant upregulation of hedgehog pathway genes was found in fatty diet groups. In comparison with the control group, Shh Ihh, Hhip, Ptch1, Smo, Gli1, Gli2, and Gli3 were upregulated in D-1. In D-2 Shh, Hhip, and Smo expressions were upregulated, Ihh exhibited downregulation as compared to control. CONCLUSION: Excess fat deposits in liver due to chronic consumption of high-fat diet results in anomalous architecture and functioning. High-fat diet induced significant variations in Hh pathway genes expression; especially Shh, Ihh, Hhip, Ptch1, Smo, Gli1, Gli2, and Gli3 were upregulated. Infiltration of inflammatory cells ( ), widened sinusoidal spaces (▲), cellular necrosis, and micro vesicular steatotic hepatocytes (*) were shown in the liver. Significant collagen deposition in both HFD groups i.e. D-1 and D-2 confirmed liver fibrosis. Excessive intake of dietary fats impaired normal liver functioning and liver inflammation triggered Hh signaling in adult rats.

Dichotomous role of autophagy in cancer.

Autophagy is an evolutionary conserved catabolic process that plays physiological and pathological roles in a cell. Its effect on cellular metabolism, the proteome, and the number and quality of organelles, diversely holds the potential to alter cellular functions. It acts paradoxically in cancer as a tumor inhibitor as well as a tumor promoter. In the early stage of tumorigenesis, it prevents tumor initiation by the so-called "quality control mechanism" and suppresses cancer progression. For late-staged tumors that are exposed to stress, it acts as a vibrant process of degradation and recycling that promotes cancer by facilitating metastasis. Despite this dichotomy, the crucial role of autophagy is evident in cancer, and associated with mammalian targets of rapamycin (mTOR), p53, and Ras-derived major cancer networks. Irrespective of the controversy regarding autophagic manipulation, promotion and suppression of autophagy act as potential therapeutic targets in cancer treatment and may provide various anticancer therapies.

A Decade of Mighty Lipophagy: What We Know and What Facts We Need to Know?

Lipids are integral cellular components that act as substrates for energy provision, signaling molecules, and essential constituents of biological membranes along with a variety of other biological functions. Despite their significance, lipid accumulation may result in lipotoxicity, impair autophagy, and lysosomal function that may lead to certain diseases and metabolic syndromes like obesity and even cell death. Therefore, these lipids are continuously recycled and redistributed by the process of selective autophagy specifically termed as lipophagy. This selective form of autophagy employs lysosomes for the maintenance of cellular lipid homeostasis. In this review, we have reviewed the current literature about how lipid droplets (LDs) are recruited towards lysosomes, cross-talk between a variety of autophagy receptors present on LD surface and lysosomes, and lipid hydrolysis by lysosomal enzymes. In addition to it, we have tried to answer most of the possible questions related to lipophagy regulation at different levels. Moreover, in the last part of this review, we have discussed some of the pathological states due to the accumulation of these LDs and their possible treatments under the light of currently available findings.

GABRA1 and GABRA6 gene mutations in idiopathic generalized epilepsy patients.

The GABA receptor is an important epilepsy-associated candidate gene, and has always been a focus in etiology and in the treatment of epilepsy. This study explores the genetic association between GABA receptor gene polymorphisms and epilepsy in a cohort of the Pakistani population. A case-control study was conducted on 150 patients with idiopathic generalized epilepsy (IGE) and 150 controls. Blood samples were collected, and genomic DNA was extracted and amplified using polymerase chain reaction (PCR). The amplified products were subsequently genotyped by Sanger sequencing and the results were analyzed using the chi-square test. Among the five mutational sites observed, two GABRA1 (rs2279020 and novel c.1016_1017insT) and two GABRA6 (rs3219151 and novel c.1344C>G) were found to be significantly associated with IGE. Amino acid alignment showed that a novel insertion mutation, c.1016_1017insT, in GABRA1 disrupted the reading frame and was possibly damaging, whereas c.1344C>G in GABRA6 was responsible for a synonymous mutation. Therefore, both the GABA receptor genes may play critical roles in the development of epilepsy in Pakistani patients.

Psychological impacts of COVID-19 and satisfaction from online classes: disturbance in daily routine and prevalence of depression, stress, and anxiety among students of Pakistan.

The present study investigated the (i) socio-demographic predictors of psychological distress, (ii) socio-demographic predictors of satisfaction from online classes, and (iii) the relationship between psychological distress and satisfaction from online classes among university students of Pakistan during the COVID-19 pandemic. An online questionnaire-based survey was conducted. A total of 2220 respondents that was enrolled at the University of the Punjab (PU), University of Management and Technology (UMT), and the University of Central Punjab (UCP) were involved in the current study. Data were collected at a 64% response rate and analyzed with SPSS IBM Version 21.0. Results revealed that approximately 41% of the students were facing severe psychological distress while about 65% were found unsatisfied with online classes. Besides, a linear negative relationship between the independent variable, i.e. psychological distress and the dependent variable, i.e. satisfaction from online classes was found. Therefore, to minimize the level of psychological distress and increase students' satisfaction with online classes it is highly recommended to take precautionary measures by the relevant stakeholders.

High-Fat Diet Induced Hedgehog Signaling Modifications during Chronic Kidney Damage.

Excessive consumption of dietary fats leads to the deposition of unnecessary metabolites and multiple organ damage. Lipids, important key regulators of Hedgehog signaling, are involved in triggering fibrotic chronic kidney disease. The present study encompasses the assessment of renal morphofunctional modifications and alteration of lipid metabolism influencing the changes in gene expression of hedgehog signaling pathway genes. Fifteen male Rattus norvegicus of 200 ± 25 grams weight were equally divided into three groups: control (standard rat chow), D-1 (unsaturated high-fat diet) and D-2 (saturated high-fat diet). Animals were provided with respective diets and were followed for 16 weeks. Both HFD-fed groups did not show overall body weight gain as compared to the control. While significant downregulation of hedgehog pathway genes was found in fatty diet groups. In comparison with the control group, Shh, Gli1, Gli2, and Gli3 were downregulated after the consumption of both unsaturated and saturated fatty diets. Ihh and Smo exhibit a similar downregulation in the D-1 group, but an upregulation was detected in the D-2 group. D-2 group also had an increased serum urea concentration as compared to the control (P = 0.0023). Furthermore, renal histopathology revealed tubular necrosis, glomerular edema, glomerular shrinkage, and hypocellularity. Collagen deposition in both HFD groups marks the extent of fibrosis summary figure. Extravagant intake of dietary fats impaired normal kidney functioning and morphofunctionally anomalous kidney triggers on Hh signaling in adult rats. These anomalies can be linked to an escalated risk of chronic kidney disease in adults strongly recommending the reduced uptake of fatty diets to prevent impaired metabolism and renal lipotoxicity.

COVID-19 containment and its unrestrained impact on epilepsy management in resource-limited areas of Pakistan.

The current pandemic of coronavirus disease 2019 (COVID-19) that led to an unprecedented crisis with significant health, social, and economic repercussions presented more serious concerns for those living with some chronic conditions such as epilepsy. This study was aimed to find out impact of the COVID-19 pandemic on management of epilepsy. A cross-sectional study was conducted through telephone interviews, targeting 213 caregivers of pediatric patients with epilepsy, belonging to underserved areas of Faisalabad, Punjab, Pakistan. A simple questionnaire was designed to record the responses of participants relevant to the direct and indirect effects of COVID-19 pandemic and their knowledge about possible ways that can be accessed for the management of epilepsy during an ongoing pandemic. The current study, which holds 77% of the respondents from rural areas and 23% from urban settings, showed that partial measures of lockdown taken to stop or slow the spread of COVID-19 resulted in adverse economic and health outcomes in the said population including cancelation of follow-up visits, worsening of seizures, job loss, burden of antiepileptic drugs (AEDs) costs, and discontinuation of medicines. Furthermore, knowledge about alternative ways to access health facilities was found very poor among caregivers. Income sources of poor people disrupted by lockdown can lead to unintentional nonadherence to medication, which is a clear picture of inequitable distribution of resources. This study highlights the major issues faced by the caregivers during this ongoing pandemic of COVID-19.

An Update on Novel Therapeutic Warfronts of Extracellular Vesicles (EVs) in Cancer Treatment: Where We Are Standing Right Now and Where to Go in the Future.

Extracellular vesicles (EVs) are a heterogeneous group of membrane-bounded vesicles that are believed to be produced and secreted by presumably all cell types under physiological and pathological conditions, including tumors. EVs are very important vehicles in intercellular communications for both shorter and longer distances and are able to deliver a wide range of cargos including proteins, lipids, and various species of nucleic acids effectively. EVs have been emerging as a novel biotherapeutic platform to efficiently deliver therapeutic cargos to treat a broad range of diseases including cancer. This vast potential of drug delivery lies in their abilities to carry a variety of cargos and their ease in crossing the biological membranes. Similarly, their presence in a variety of body fluids makes them a potential biomarker for early diagnosis, prognostication, and surveillance of cancer. Here, we discuss the relatively least and understudied aspects of EV biology and tried to highlight the obstacles and limitations in their clinical applications and also described most of the new warfronts to beat cancer at multiple stages. However, much more challenges still remain to evaluate EV-based therapeutics, and we are very much hopeful that the current work prompts further discovery.

An In Vivo Study on Intoxicating Effects of Nerium oleander Water Based Extract on Multiorgans of Wistar Rat.

This study was aimed to find histological changes in the extrahepatic organs, hepatic iron deposition, and gene expression of some iron regulatory proteins in rats after sterile muscle abscess during the acute intoxication of Nerium oleander leaves decoction. 10 ml/kg of the leaves extract was injected intramuscularly in Wistar rats (200-225 g, n = 4). Control animals received saline injection of matched volume. Animals were anesthetized and sacrificed after 3, 6, 12, and 24 h after administration of decoction. Lungs, kidney, spleen, and liver were extracted and processed for histopathological examination while portion of liver tissue was proceeded for iron regulatory gene expression quantification. Sections of all studied organs were found with signs of cellular dysfunction with infiltration of variety of leucocytes. In the lungs section at 3 h time point mononuclear cell infiltrates were observed while in alveolar tissue at 24 h time point dilation and even collapse in some of the alveoli were evident. In kidney sections distortion of renal tubules and epithelial cells with shrinkage of glomeruli was noted at all studied time points. In the splenic section of 12 h time point, degeneration, depopulation, and shrinkage of white pulp have been noted. Distension of the red pulp along with activation of splenic follicles was evident after 24 h onset of APR. Significant changes in the expression of acute phase cytokine and iron regulatory genes were noted. IL-6 and Hepc gene expression were strongly upregulated up to 12 h whereby Tf gene expression showed an early upregulation at 3 h time point followed by downregulation on later points while Hjv gene expression showed an overall downregulation at all study time points compared to control. It is concluded that inherent toxins present in the N. oleander can induce acute phase response and cause severe histological changes in the organs and marked changes in the regulation of iron regulatory proteins thus cannot be practiced routinely.

Multifactorial role of long non-coding RNAs (LncRNAs) in hematopoiesis.

Human genome project unveiled that only 1.5.-2.0.% of the genome is protein coding. ENCODE and related studies showed that most part of the genome transcribed into RNAs, and most of them do not code for a functional proteins, hence the name non-coding RNAs (ncRNAs). ncRNAs are small ncRNAs (less than 200 nucleotides) and long ncRNAs (longer than 200 nucleotides up to 10 kb). They act as a direct link between highly ordered chromosome structures, gene expression and serve as a bridge between genome and chromatin modification complexes as guides, scaffolds, and decoys. Highly regulated hematopoietic differentiation is required for formation of all types of blood cells. Among a variety of lncRNAs only few hematopoitic lncRNAs have been studied extensivelyand most of them are not functionally characterized. The role of these lncRNAs remains partially undetermined but their involvement in the regulation of various genes and protein synthesis has been proved even in hematopoiesis. So, the present review is a mere effort to highlight the role of lncRNAs involved in the development and regulation of hematopoiesis.

IL-32θ: a recently identified anti-inflammatory variant of IL-32 and its preventive role in various disorders and tumor suppressor activity.

Interleukin-32 theta (IL-32θ) is newly identified isoform of IL-32 which plays a vital role in inflammatory responses. Like IL-32α and IL-32ß, IL-32θ isoform acts as an intracellular inflammatory modulator. It results in reduction of IL-1ß production by attenuating the expression of PU.1 and inhibition of monocytes differentiation into macrophages. IL-32θ hinders TNF-α expression by inhibiting p38 MAPK and inhibitor of κB (IκB) as well. It also reserved STAT3-ZEB1 pathway leading to the inhibition of epithelial-mesenchymal transition (EMT) and stemness. Hence, it can be concluded that IL-32θ is an anti-inflammatory cytokine that can act as a tumor suppressor and can play vital role in colon cancer therapies. IL-32θ also plays a crucial role in immune system responses and cellular differentiation during disease pathogenesis. To our best knowledge this is the first ever review to condense the importance, precise mode of action in disease progression and latent remedial implications of IL-32θ in several inflammatory disorders.

IL-32: A Novel Pluripotent Inflammatory Interleukin, towards Gastric Inflammation, Gastric Cancer, and Chronic Rhino Sinusitis.

A vast variety of nonstructural proteins have been studied for their key roles and involvement in a number of biological phenomenona. Interleukin-32 is a novel cytokine whose presence has been confirmed in most of the mammals except rodents. The IL-32 gene was identified on human chromosome 16 p13.3. The gene has eight exons and nine splice variants, namely, IL-32α, IL-32ß, IL-32γ, IL-32δ, IL-32ε, IL-32ζ, IL-32η, IL-32θ, and IL-32s. It was found to induce the expression of various inflammatory cytokines including TNF-α, IL-6, and IL-1ß as well as macrophage inflammatory protein-2 (MIP-2) and has been reported previously to be involved in the pathogenesis and progression of a number of inflammatory disorders, namely, inflammatory bowel disease (IBD), gastric inflammation and cancer, rheumatoid arthritis, and chronic obstructive pulmonary disease (COPD). In the current review, we have highlighted the involvement of IL-32 in gastric cancer, gastric inflammation, and chronic rhinosinusitis. We have also tried to explore various mechanisms suspected to induce the expression of this extraordinary cytokine as well as various mechanisms of action employed by IL-32 during the mediation and progression of the above said problems.

A panoramic spectrum of complex interplay between the immune system and IL-32 during pathogenesis of various systemic infections and inflammation.

Cytokines have always been of great interest due to their vast potential and participation in the progression and pathogenesis of various ailments. Interleukin-32 (IL-32) is a recently identified cytokine, whose gene is located on human chromosome 16 p13.3, with eight exons and six splice variants (IL-32α to IL-32ζ). IL-32α, the most abundant form, is secreted by different types of cells including T cells, natural killer (NK) cells, monocytes, endothelial cells and epithelial cells. It acts as a preferential mediator and effector of abnormal immune responses to multiple inflammatory and auto immune diseases including rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), etc. It was found to stimulate the induction of various chemokines, pro-inflammatory cytokines including IL-1ß, IL-6, IL-8, TNF-α and macrophage inflammatory protein-2 (MIP-2). Hence, IL-32 mediates the crucial interplay among immune system and body cells during pathogenesis of various insults. The aim of the present effort is to summarize the role, mechanism of pathogenesis and potential therapeutic applications of IL-32 in different systemic infections and diseased conditions.

Clinical and pathological features of Nerium oleander extract toxicosis in wistar rats.

BACKGROUND: Nerium oleander has been widely studied for medicinal purposes for variety of maladies. N. oleander has also been reported having noxious effects because of its number of components that may show signs of toxicity by inhibiting plasma lemma Na+, K+-ATPase. The present study was performed to scrutinize the toxic effect of N. oleander leaves extract and its clinical and pathological features in wistar rats. RESULTS: Hematological analysis showed significant variations in RBCs count (P = 0.01), Hb (P = 0.001), Hct (P = 0.0003), MCV (P = 0.013), lymphocyte count (P = 0.015), neutrophil count (P = 0.003), monocyte count (P = 0.012) and eosinophil count (P = 0.006). Histopathological studies have shown that in T1 group noticeable infiltration of inflammatory cells was found with low level of vascular damage. In T2 group, increased proportion of binucleated and inflammatory cells, hepatic necrosis, widening of sinusoidal spaces and mild level of vascular damage was observed. CONCLUSION: Taken together these findings we can conclude that N. oleander leaves extract significantly affects on experimental animals due to its toxicity. Efforts must be exerted to purify different chemical components from extract with no inflammation as this plant is utilized in folk medicine with narrow therapeutic indices.