Oregano (Origanum vulgare) Essential Oil and Its Constituents Prevent Rat Kidney Tissue Injury and Inflammation Induced by a High Dose of L-Arginine.

This study aimed to evaluate the protective action of oregano (Origanum vulgare) essential oil and its monoterpene constituents (thymol and carvacrol) in L-arginine-induced kidney damage by studying inflammatory and tissue damage parameters. The determination of biochemical markers that reflect kidney function, i.e., serum levels of urea and creatinine, tissue levels of neutrophil-gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1), as well as a panel of oxidative-stress-related and inflammatory biomarkers, was performed. Furthermore, histopathological and immunohistochemical analyses of kidneys obtained from different experimental groups were conducted. Pre-treatment with the investigated compounds prevented an L-arginine-induced increase in serum and tissue kidney damage markers and, additionally, decreased the levels of inflammation-related parameters (TNF-α and nitric oxide concentrations and myeloperoxidase activity). Micromorphological kidney tissue changes correlate with the alterations observed in the biochemical parameters, as well as the expression of CD95 in tubule cells and CD68 in inflammatory infiltrate cells. The present results revealed that oregano essential oil, thymol, and carvacrol exert nephroprotective activity, which could be, to a great extent, associated with their anti-inflammatory, antiradical scavenging, and antiapoptotic action and, above all, due to their ability to lessen the disturbances arising from acute pancreatic damage. Further in-depth studies are needed in order to provide more detailed explanations of the observed activities.

The role of melatonin in preventing amiodarone-induced rat liver damage.

Long-term exposure to amiodarone, an antiarrhythmic drug, can induce different organ damage, including liver. Cell damage included by amiodarone is a consequence of mitochondrial damage, reactive oxygen species production, and cell energy depletion leading to programmed cell death. In the present study, hepatoprotective potential of neurohormone melatonin (50 mg/kg/day) was evaluated in a chronic experimental model of liver damage induced by a 4-week application of amiodarone (70 mg/kg/day). The obtained results indicate that amiodarone induces an increase in xanthine oxidase activity, as well as the content of the lipid and protein oxidatively modified products and p53 levels. Microscopic analysis further corroborated the biochemical findings revealing hepatocyte degeneration, apoptosis, and occasional necrosis, with the activation of Kupffer cells. Coadministration of melatonin and amiodaron prevented an increase in certain damage associated parameters, due to its multiple targets. In conclusion, the application of melatonin together with amiodarone prevented an increase in tissue oxidative damage parameters and moderately prevented liver cell apoptosis, indicating that the damage of hepatocytes provoked by amiodarone supersedes the protective properties of melatonin in a given dose.

Melatonin treatment prevents carbon-tetrachloride induced rat brain injury.

Introduction: Herein the neuroprotective properties of melatonin, a highly effective antioxidant, administered in a single dose 50 mg/kg intraperitoneally, were investigated in the brain tissue of Wistar rats acutely exposed to the toxin carbon-tetrachloride (1 mL/kg, intraperitoneally). Methods: To assess the degree of whole encephalic mass damage, biochemical parameters related to lipid and protein oxidation, antioxidant enzymes (catalase and superoxide dismutase), glutathione and inducible nitric oxide/arginase pathways were determined. Results: The results showed that carbon-tetrachloride impaired the function of antioxidant enzymes (reduced catalase and superoxide dismutase activities) and reduced glutathione-metabolizing enzymes (reduced glutathione, glutathione S-transferase and peroxidase activity). Furthermore, carbon-tetrachloride increased lipid peroxidation and protein oxidative damage in the brain tissue, as well as myeloperoxidase and inducible nitric oxide synthase content/activities. Conclusions: The application of a single dose of melatonin post intoxication has been able to reverse the disturbance in the function of antioxidant enzymes and alleviate the tissue damage caused by oxidative stress, indicating that melatonin could be a potential therapeutic agent in oxidative-damage related neurodegenerative disorders.

Melatonin as a Promising Anti-Inflammatory Agent in an In Vivo Animal Model of Sepsis-Induced Rat Liver Damage.

Melatonin (MLT), earlier described as an effective anti-inflammatory agent, could be a beneficial adjunctive drug for sepsis treatment. This study aimed to determine the effects of MLT application in lipopolysaccharide (LPS)-induced sepsis in Wistar rats by determining the levels of liver tissue pro-inflammatory cytokines (TNF-α, IL-6) and NF-κB as well as hematological parameters indicating the state of sepsis. Additionally, an immunohistological analysis of CD14 molecule expression was conducted. Our research demonstrated that treatment with MLT prevented an LPS-induced increase in pro-inflammatory cytokines TNF-α and IL-6 and NF-κB levels, and in the neutrophil to lymphocyte ratio (NLR). On the other hand, MLT prevented a decrease in the blood lymphocyte number induced by LPS administration. Also, treatment with MLT decreased the liver tissue expression of the CD14 molecule observed after sepsis induction. In summary, in rats with LPS-induced sepsis, MLT was shown to be a significant anti-inflammatory agent with the potential to change the liver's immunological marker expression, thus ameliorating liver function.

Melatonin arrests excessive inflammatory response and apoptosis in lipopolysaccharide-damaged rat liver: A deeper insight into its mechanism of action.

Sepsis is a life-threatening organ dysfunction. An animal model mimicking sepsis utilizes lipopolysaccharide (LPS), an endotoxin recognized as the most potent bacterial mediator of sepsis. Melatonin (MLT), an effective anti-inflammatory and antioxidant agent, is a promising adjunctive drug for sepsis. This study aimed to estimate the potential of MLT in preventing LPS-induced liver damage in Wistar rats by determining the levels of serum and tissue biochemical markers that reflect liver state and function, i.e., serum levels of transaminases and albumin, as well as a panel of oxidative stress-related biomarkers. Additionally, a pathohistological analysis of liver tissue was conducted. Pre-treatment with MLT prevented an LPS-induced increase in serum and tissue liver damage markers and a decrease in the tissue antioxidant capacity, in both enzymatic and non-enzymatic systems. Micromorphological liver tissue changes mirrored the alterations observed in the biochemical status. In rats with LPS-induced sepsis, melatonin was shown to be a crucial antioxidant and anti-inflammatory agent, with vital roles in the alleviation of oxidative stress, causing an increase of the antioxidant capacities and the improvement of the liver's microscopic appearance.

In silico approach for the development of novel antiviral compounds based on SARS-COV-2 protease inhibition.

The COVID-19 pandemic emerged in 2019, bringing with it the need for greater stores of effective antiviral drugs. This paper deals with the conformation-independent, QSAR model, developed by employing the Monte Carlo optimization method, as well as molecular graphs and the SMILES notation-based descriptors for the purpose of modeling the SARS-CoV-3CLpro enzyme inhibition. The main purpose was developing a reproducible model involving easy interpretation, utilized for a quick prediction of the inhibitory activity of SAR-CoV-3CLpro. The following statistical parameters were present in the best-developed QSAR model: (training set) R 2 = 0.9314, Q 2 = 0.9271; (test set) R 2 = 0.9243, Q 2 = 0.8986. Molecular fragments, defined as SMILES notation descriptors, that have a positive and negative impact on 3CLpro inhibition were identified on the basis of the results obtained for structural indicators, and were applied to the computer-aided design of five new compounds with (4-methoxyphenyl)[2-(methylsulfanyl)-6,7-dihydro-1H-[1,4]dioxino[2,3-f]benzimidazol-1-yl]methanone as a template molecule. Molecular docking studies were used to examine the potential inhibition effect of designed molecules on SARS-CoV-3CLpro enzyme inhibition and obtained results have high correlation with the QSAR modeling results. In addition, the interactions between the designed molecules and amino acids from the 3CLpro active site were determined, and the energies they yield were calculated. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02170-8.

Acutely applied melatonin prevents CCl4-induced testicular lesions in rats: the involvement of the oxidative capacity and arginine metabolism

Abstract Carbon tetrachloride (CCl4) represents an organic chemical that causes reactive oxygen species derived organ disturbances including male infertility. Melatonin (MLT) is a neurohormone with strong antioxidant capacity, involved in numerous physiological processes. In this study we evaluated the capability of MLT, administered in a single dose of 50 mg/kg, to preserve the testicular tissue function after an acute administration of CCl4 to rats. The disturbance in testicular tissue and the effects of MLT after CCl4 exposure were estimated using biochemical parameters that enabled us to determine the tissue (anti)oxidant status and the intensity of arginine/nitric oxide metabolism. Also, the serum levels of testosterone and the histopathological analysis of tissue gave us a better insight into the occurring changes. A significant diminution in tissue antioxidant defences, arginase activity and serum testosterone levels, followed by the increased production of nitric oxide and extensive lipid and protein oxidative damage, was observed in the CCl4-treated group. The application of MLT after the CCl4 caused changes, clearly visible at both biochemical and histological level, which could be interpreted mainly as a consequence of general antioxidant system stimulation and a radical scavenger. On the other hand, the application of MLT exerted a limited action on the nitric oxide signalling pathway.

Thymol regulates the functions of immune cells in the rat peritoneal cavity after l-arginine-induced pancreatitis.

AIMS: The present study aimed to evaluate the protective action of thymol towards l-arginine-induced acute pancreatitis (AP) by studying the function of rat peritoneal immune cells. MAIN METHODS: Rat peritoneal exudate cells (PECs), obtained 24 h after the injection of l-arginine (350 mg/100 g of b.w.), were evaluated for mitochondrial activity (MTT assay), adherence capacity (methylene-blue assay), and phagocyte enzyme activity (myeloperoxidase, MPO, assay). The activity of α-amylase and free MPO, as well as the concentration of reactive oxygen species (ROS, i.e. O2-), were determined in the peritoneal exudate fluid. Also, serum α-amylase activity determination and pancreatic tissue pathohistological analysis were performed. KEY FINDING: The administered thymol (50 and 100 mg/kg, per os) caused a significant decrease in the PEC mitochondrial activity and adherence capacity when compared with these functions of PECs isolated from rats with AP. A decrease in cellular MPO activity, as well as in the levels of ROS, α-amylase, and free MPO in peritoneal exudates was found in animals treated with thymol compared to the control animals with AP. Additionally, thymol administration prevented an increase in serum α-amylase activity, accompanied by the decrease in pancreatic tissue damage that follows l-arginine application. SIGNIFICANCE: The present results showed that thymol exerts significant immunomodulatory properties and a potential to silence PEC functions in inflammatory conditions such as the AP induced by l-arginine.

Lycopene and Caffeic Acid Phenethyl Ester Affect Caspase-3 Activity, but Do Not Alter the NO Pathway in Lung Tissue Damage Induced by Cisplatin.

INTRODUCTION: Antioxidants such as lycopene (LCP) and caffeic acid phenethyl ester (CAPE) represent ideal molecules for the treatment of different reactive oxygen species (ROS) associated disorders. Cisplatin is a chemotherapeutic agent, causing an increase in ROS and DNA damage, with numerous side effects, which include lung toxicity. In the presents study, we evaluated and mutually compared the potential of LCP and CAPE in preventing cisplatin-induced rat lung damage. METHODS: The study was done using pathohistological analysis and a panel of biochemical parameters that reflect lung oxidative tissue damage, inflammation, and apoptosis. RESULTS: The obtained results suggest that cisplatin (10 mg/kg) causes significant disturbances in the lung tissue morphology, followed by an increase in lipid peroxidization and protein modification. Also, a pronounced inflammatory response and cell apoptosis cascade activation was noted. Both LCP and CAPE were able to mitigate the changes, to a different extent, in oxidative damage and apoptosis progression induced by cisplatin. However, they both had limited effect on inflammation since they only prevented an increase in myeloperoxidase activity but had not been able to prevent the NO generation. CONCLUSION: It is hard to be exact in saying whether LCP or CAPE is better in preventing cis-platin-induced lung damage since they obviously possess different mechanisms of action.

An Impact of Psychological Stress on the Interplay between Salivary Oxidative Stress and the Classic Psychological Stress-Related Parameters.

Both oxidative and psychological (mental) stress are the likely culprits for several acute and chronic health disturbances, and adequate tests mimicking that are needed. Herein, in controlled laboratory surroundings, a PEBL (Psychology Experiment Building Language) test battery was used to evoke stress-related biological responses followed by tracking changes in saliva parameters. The study objectives were to determine the impact of psychological stress on selected salivatory parameters and to assess the correlation between the determined oxidative and stress parameters. The study was conducted on 36 healthy young subjects, mainly females (n = 24). Before and following the completion of a battery of four PEBL tests, subjects' saliva samples were collected. Stress-evoking changes in total antioxidant capacity and nitrite/nitrate levels, as oxidative stress parameters, and cortisol and immunoglobulin A (IgA), as parameters of psychological stress, were established and mutually correlated by comparing the values of the evaluated parameters pre- and post-PEBL test. The results showed that there is no change in the total salivary antioxidant capacity (p > 0.05); however, there was a significant increase in nitrites/nitrates levels after the PEBL test (p = 0.007). On the other hand, the determined cortisol levels after the test battery were found to be statistically significantly increased (p = 0.025) when compared to the values obtained before the test, while the levels of IgA were found to be statistically significantly decreased (p < 0.001). The only statistically significant correlation between the changes in the studied parameters was found to be the one between cortisol and IgA levels (Spearman's Rö = -0.4). These results suggest that the short-term stress induced by the PEBL test does evoke changes in the salivary mental stress-related parameters (an increase in cortisol and nitrite/nitrate levels, and a decrease in IgA), but not in the total antioxidant capacity. They also indicate that the constructed PEBL four-test battery might represent an adequate laboratory stress-inducing paradigm.

The relationship between occupational stress, health status, and temporary and permanent work disability among security guards in Serbia.

Purpose. This study aimed to examine the influence of occupational stress on health status and work disability among security guards in Serbia. Methods. Three hundred and ninty nine male security guards (aged 25-65 years) were examined during regular medical preventive check-ups at the Institute of Occupational Health. Data on their health status and permanent and temporary work disability were obtained, and correlations with the levels of occupational stress (measured by occupational stress index [OSI] questionnaire) were analysed. Results. A high prevalence of health impairments, including diabetes (38.8%), dyslipidaemia (82.7%), hypertension (69.9%) and metabolic syndrome (77.7%), was found. Highly significant correlations were shown between reported levels of total stress at work (total OSI score) and measured values of glucose, lipids, blood pressure, heart rate, Framingham cardiovascular risk scale, occurrence of diabetes and impaired fasting glucose, dyslipidaemia, hypertension, metabolic syndrome, coronary heart disease, cerebrovascular insults, degenerative eye-fundus changes, and temporary and permanent work disability. All of these correlations remained significant even after adjustments for age, body mass index and smoking status. Regression analysis confirmed the independent effect of occupational stress on the analysed parameters. Conclusions. There is a significant independent impact of occupational stress on development of health impairments and work disability among security guards.

Interstitial Cells of Cajal and Neural Structures in the Human Fetal Appendix.

BACKGROUND/AIMS: The interstitial cells of Cajal (ICC) are located within and around the digestive tract's muscle layers. They function as intestinal muscle pacemakers and aid in the modification of enteric neurotransmission. The appendix's unique position requires an appropriate contraction pattern of its muscular wall to adequately evacuate its contents. We investigated the development and distribution of nervous structures and ICC in the human fetal appendix. METHODS: Specimens were exposed to anti-c-kit (CD117) antibodies to investigate ICC differentiation. Enteric plexuses were examined using anti-neuron-specific enolase, and the differentiation of smooth muscle cells was studied with anti-desmin antibodies. RESULTS: During weeks 13-14, numerous myenteric plexus ganglia form an almost uninterrupted sequence throughout the body and apex of the appendix. Fewer ganglia were present at the submucosal border of the circular muscle layer and within this layer. A large number of ganglia appear within the circular and longitudinal muscle layers in a later fetal period. The first ICC subtypes noted were of the myenteric plexus and the submucous plexus. In the later fetal period, the number of intramuscular ICC markedly rises, and this subtype becomes predominant. CONCLUSIONS: The ICC and nervous structure distribution in the human fetal appendix are significantly different from all other parts of the small and large intestine. The organization of ICC and the enteric nervous system provides the basis for the specific contraction pattern of the muscular wall of the appendix.

Melatonin modulates acute cardiac muscle damage induced by carbon tetrachloride - involvement of oxidative damage, glutathione, and arginine and nitric oxide metabolism.

The present study was designed to evaluate the cardioprotective effects of melatonin (a single dose of 50 mg·kg-1), a naturally occurring polypharmacological molecule, in Wistar rats acutely exposed to carbon tetrachloride (CCl4). This was done for the first time by tracking different biochemical parameters that reflect rat heart antioxidative and oxidative capacities, nitric oxide and arginine metabolism, and the glutathione cycle. Additionally, the extrinsic apoptosis pathway related parameters were studied. Acute exposure to CCl4 led to an increase in the studied tissue oxidant parameters (hydrogen peroxide, malondialdehyde, and carbonylated protein content), as well as the activity alteration of antioxidant (catalase, superoxide dismutase, and peroxidase) and glutathione-metabolizing (glutathione peroxidase, S-transferase, and reductase) enzymes. Furthermore, CCl4 caused a disturbance in the tissue myeloperoxidase, nitric oxide, citrulline, arginase, and inducible nitric oxide synthase content and activities and in two apoptosis-related parameters, caspase-3 and FAS ligand. Melatonin as a post-treatment prevented the changes induced by CCl4 to a differing extent, and in some cases, it was so potent that it completely abolished any tissue disturbances. This study is a promising starting point for further research directed to the development of melatonin treatment in cardiac tissue associated diseases.

Local and Systemic Oxidative Stress in Balkan Endemic Nephropathy Is Not Associated with Xanthine Oxidase Activity.

Balkan endemic nephropathy (BEN) represents a chronic tubulointerstitial nephropathy which is followed by the progression of kidney fibrosis to end-stage kidney failure. The critical involvement of poisons in food (aristolochic acid (AA), ochratoxin, and heavy metals) and selenium deficiency are among nutritive factors which contribute to the pathogenesis of BEN, due to reactive oxygen species (ROS) liberation and/or decreased antioxidative defence system. The aim of the study is to distinguish a possible systemic and local origin of ROS through the measurement of xanthine oxidase (XO) activity in urine and plasma, along with the determination of the oxidative changes in lipids and proteins. The study included 50 patients with BEN and 38 control healthy subjects. We noted increased levels of both thiobarbituric acid-reactive substances (TBARS) and advanced oxidation protein products (AOPPs) in the plasma of patients with BEN, compared to the control group (p < 0.001). The urinary levels of AOPPs were higher in patients with BEN in comparison to the control (p < 0.001). The specific activity of XO was significantly lower in plasma and urine in BEN samples, compared to controls (p < 0.005). Based on these results, we hypothesize that XO might not be considered a direct systemic or local contributor to ROS production in BEN, most probably because of the diminished kidney functional tissue mass and/or AA-induced changes in purine nucleotide conformation. The increased AOPP and TBARS level in both plasma and urine in BEN may predict ROS systemic liberation with toxic local effects.

Xanthine Oxidase/Dehydrogenase Activity as a Source of Oxidative Stress in Prostate Cancer Tissue.

Prostate cancer (PC) is one of the most frequent malignancies. Better biomarkers are constantly wanted, such as those which can help with the prediction of cancer behavior. What is also needed is a marker which may serve as a possible therapeutic target. Oxidative stress (OS), which is a hallmark of cancer, is included in the pathogenesis and progression of PC. We have conducted the present study to determine whether xanthine oxidase/dehydrogenase activity is the source of OS in prostate tissue. We have also determined the concentration of TBA-reactive substances (TBARS) and advanced oxidation protein products (AOPP), as well as the activity of catalase. Xanthine oxidase (XO) activity is significantly higher (p < 0.001) in tumor tissue when compared to the control healthy tissue. The concentration of TBARS (p < 0.001) and AOPP (p < 0.05) are also higher in tumor tissue. Catalase has raised its activity (p < 0.05) versus the control. There is also a strong correlation between XO activity and prostate-specific antigen (PSA) levels in the serum. These results indicate a significant role of XO activity in OS in prostate carcinogenesis, and it could be a possible theranostic biomarker, which can be important for a better understanding of the disease, its evolution, and prognosis. A promising treatment may be using XO inhibitors such as allopurinol as adjuvant therapy.

In silico development of anesthetics based on barbiturate and thiobarbiturate inhibition of GABAA.

The inhibition of GABAA can be used in general anesthesia. Although, barbiturates and thiobarbiturates are used in anesthesia, the mechanism of their action hasn't been established. QSAR modeling is a wieldy used technique in these cases and this study presents the QSAR modeling for a group of barbiturates and thiobarbiturates with determined anesthetic activity. Developed QSAR models were based on conformation independent and 2D descriptors as well as field contribution. As descriptors used for developing conformation independent QSAR models, (SMILES) notation and local invariants of the molecular graph were used. Monte Carlo optimization method was applied for building QSAR models for two defined activities. Methodology for developing QSAR models capable of dealing with the small dataset that integrates dataset curation, "exhaustive" double cross-validation and a set of optimal model selection techniques including consensus predictions was used. Two-dimensional descriptors with definite physicochemical meaning were used and modeling was done with the application of both partial least squares and multiple linear regression models with three latent variables related to simple and interpretable 2D descriptors. Different statistical methods, including novel method - the index of ideality of correlation, were used to test the quality of the developed models, especially robustness and predictability and all obtained results were good. In this study, obtained results indicate that there is a very good correlation between all developed models. Molecular fragments that account for the increase/decrease of a studied activity were defined and further used for the computer-aided design of new compounds as potential anesthetics.

Morphometric analysis of structural renal alterations and beneficial effects of aminoguanidine in acute kidney injury induced by cisplatin in rats.

Since cisplatin-induced nephrotoxicity has very important clinical consequences, the purpose of this study was to determine the potential protective effect of aminoguanidine on the acute kidney injury caused by cisplatin. Experiments were done on 40 Wistar rats divided into four groups. The CIS group received cisplatin in a single dose of 8 mg/kg, while the CISAG group received the same dose of cisplatin and aminoguanidine (100 mg/kg) by intraperitoneal injections. Animals in the AG group received only aminoguanidine (100 mg/kg) and those in the C group received saline. Quantitative evaluation of structural and functional alterations in the kidneys was performed by analysis of biochemical and parameters of oxidative stress and by histological and morphometric analysis of renal sections. Histological sections of kidney showed structural damage of proximal tubules and glomeruli that were induced by cisplatin. Morphometric analysis revealed statistically significant differences in the area of proximal tubules and the size and cellularity of glomeruli between the CIS and CISAG groups. Glomerular basement membrane thickness was increased in the CIS group, while aminoguanidine attenuated these changes in the CISAG group of rats. Our results suggest that aminoguanidine acts protectively and repairs structural and functional damage of kidney by engaging the existent antioxidative potential at the level of renal tissue.

Design and development of novel therapeutics for brucellosis treatment based on carbonic anhydrase inhibition.

Carbonic anhydrase is a metalloprotein, an enzyme with strong inhibition in antibacterial treatment. This study presents QSAR modeling for a series of 41 chemical compounds, 40 sulfonamides and one sulfamate, including 13 clinically tested drugs as carbonic anhydrase inhibitors based on the Monte Carlo optimization with molecular descriptors based on the SMILES notation and local invariants of the molecular graph, and field 3D based methods. Conformation independent QSAR models were developed for three random splits and a 3D QSAR model for one random split into the training and test sets. The statistical quality of the developed models, including robustness and predictability, was tested using various statistical approaches and the results that were obtained were very good. An excellent correlation between the results from the conformation independent and the 3D QSAR model was obtained. A novel statistical metric known as the index of ideality of correlation was used for the final assessment of the model, and the obtained results were good. Molecular fragments responsible for the increases and decreases of a studied activity were defined and further used for the computer-aided design of new compounds as potential carbonic anhydrase inhibitors. Molecular docking was applied for the final assessment of the developed QSAR model and designed inhibitors, and an excellent correlation between the results from QSAR modeling and molecular docking studies was obtained.Communicated by Ramaswamy H. Sarma.

Caffeic acid phenethyl ester attenuates changes in pancreatic tissue damage biomarkers induced by cisplatin.

Application of cisplatin (CP) for the treatment of different cancers is known to cause pancreatitis through an increase in reactive oxygen species production and promotion of inflammation. Caffeic acid phenethyl ester (CAPE), the main activity carrier of propolis extracts, was previously found to possess numerous beneficial properties. This study aims to determine for the first time the potential of CAPE in preventing CP-induced pancreatic tissue damage by studying the changes occurring on both biochemical and microscopic levels. The levels of serum α-amylase and a panel of pancreatic tissue biomarkers related to tissue injury (reduced glutathione, xanthine oxidase, malondialdehyde, and protein carbonylated concentration) and inflammation (myeloperoxidase, nitric oxide, and umor necrosis factor alpha) were studied in male Wistar rats treated with either CP alone or with CP and CAPE. Additionally, microscopic analysis of pancreatic tissue would be conducted as well. Application of CAPE together with CP statistically significantly prevented the disturbance in all here-studied pancreatic tissue damage and inflammation-related biomarkers. The changes in pancreas biochemical status was followed by morphological disturbance. The results of the present study suggest that CAPE could act as a protective agent in pancreatic damage that arises after CP application.