Histopathological Effects Research Articles

Histopathological Effects of Sodium Saccharin Toxicity on Liver and Kidney of Rats in Duhok City-Iraq

Histopathological Effects of Sodium Saccharin Toxicity on Liver and Kidney of Rats in Duhok City-Iraq

Histopathological Effects of Anabolic Androgenic Steroids (Nandrolone Decanoate) on Heart, Liver and Kidney of Male Local Rabbits

Histopathological Effects of Anabolic Androgenic Steroids (Nandrolone Decanoate) on Heart, Liver and Kidney of Male Local Rabbits

Histopathology of thermal effects in endoscopic ear surgery: An experimental animal study.

The potential risk of thermal damage in the transcanal endoscopic ear surgery has been a concerning issue. This study aimed to investigate the histopathological effects of heat exposure of different durations in external auditory canal (EAC) skin and facial nerve tissues. This study was conducted on 20 rabbits assigned equally to five groups according to the endoscope-transmitted heat exposure duration: Control group (no exposure), 2, 10, 15, and 30 min. At the end of the procedure, EAC skin and the tympanic segment of facial nerve tissue samples were taken surgically and histopathologically examined. Significant histopathological thermal damage findings in external auditory canal skin and facial nerve tissues were observed under endoscope-transmitted heat exposure longer than 15 and 10 min, respectively. This study demonstrated that prolonged exposure of the endoscope-transmitted heat can cause histopathological thermal damage in EAC skin and facial nerve on rabbit subjects.

Histopathological and Anti-hemorrhoid Effect of the Leaf Extract of Ocimum gratissimum in Croton Oil-induced Hemorrhoid

The use of medicinal plants in the treatment of various diseases dates back into centuries. Hemorrhoids are swollen veins in the lower rectum or anus, ranging from being acute to a complicated state; and affecting several millions of people worldwide. This study evaluates the histopathological and anti-hemorrhoid effect of the leaf extract of Ocimum gratissimum in croton oil-induced hemorrhoid in wistar rats. Hemorrhoids was induced to the experimental animals using croton oil, following standard methods. Thirty five (35) wistar rats were randomly grouped into five classes (A, B, C, D and E) of seven rats each. Groups A, B and C served as normal control (un-induced, untreated), negative control (induced, untreated) and standard control (induced, treated with standard drug; Daflon) respectively while groups D and E served as treatment groups and were administered 100 and 400 mg/kg dose of ethanol leaf extract of Ocimum gratissimum respectively. All the rats (except the group A) animals were induced with croton oil and were thereafter treated for fourteen days (two weeks). The body weight of the animals were monitored throughout the experimental period and percentage rectal water content, anorectal coefficient as well as histopathological assay were carried out at the end of the fourteen days, using standard methods. Results showed a significant decrease (p>0.05) in body weight of the untreated group while there was a marked increase in the body weight of the animals in the extract treated groups from day 1 to the 14th day. The result of the percentage rectal water content as well as anorectal coefficient of the untreated group showed a significant increase (p<0.05) (76%) when compared to the extract treated groups (67%), while the histopathological studies showed a reversal of the inflammatory and necrotic conditions of the induced anorectal portion for the extract treated animals. From the result of this study, it could be concluded that the leaf extract of Ocimum gratissimum could help to mitigate anorectal disorders and contribute significantly to improved health.

A histological observation on heavy metal induced implications on respiratory epithelium and its causative impact on a catfish Heteropneustes fossilis (Bloch)

Present study is based on lead nitrate induced histological effect on the respiratory organs of Heteropneustes fossilis (Bloch). Lead nitrate is a heavy metal compound which used in many industries and indiscriminately drains out in water system and contaminates aquatic medium leads serious hazardous effect on respiratory epithelium of fish. Lead nitrate induced alteration on respiratory epithelium associated with the air breathing organ, suprabranchial chamber and air sacs of Heteropneustes fossilis (Bloch) and also affect the oxygen consumption capacity of fish which adversely affect its survival. Heavy metal poisoning produced remarkable histopathological deleterious effect on the accessory respiratory organ decreases the rate of oxygen consumption. Various concentration of lead nitrate showed noticeable histopathological changes which is a sign of serious effect of this heavy metal and its bioaccumulation ultimately dangerous for human consumption of contaminated fish through food chain.

Growth, immunomodulatory, histopathological, and antibacterial effects of phytobiotic-incorporated diets on Oreochromis niloticus in unchanged water

Phytobiotics are promising diet alternatives, yet their effectiveness in high-risk aquaculture conditions remains underexplored. Therefore, a 90-day feeding trial was conducted based on dietary supplementation of Nile tilapia, Oreochromis niloticus, with herbal extracts, namely, lemon balm [Melissa officinalis (MOE)], marjoram [Origanum majorana (OME)], and chamomile [Matricaria chamomilla (MCE)] with 0% water change. The treated groups were compared to groups untreated with herbs or control groups [positive control (PC; 0% water change) and negative control (NC; 20% water exchange per day]. Fish were cultured at stocking density (20 fish m-3: 1.8kg of biomass/m3). We conducted a physicochemical analysis of the water and the clinical responses, growth, and immune responses of the fish were evaluated. Furthermore, the herbal-supplemented fish were then challenged with a pathogenic Edwardseilla tarda strain and mortality was monitored. In the 1st and 2nd months, the water parameters were within the permissible limits. After that, a fatally low dissolved oxygen concentration and the highest levels of ammonia, nitrite, nitrate, and pH were recorded during the 3rd month. Blood and immune assays were conducted in the treated groups and control groups. The herbal-treated groups appeared healthy, but during the 3rd month, lethargy and decreased appetite were evident. Generally, the herbal-treated fish showed improved growth performance parameters, survival rates, and resistance against pathogenic bacteria E. tarda, particularly in the OME and MOE-treated groups compared to the positive control group. Finally, phytobiotic supplements were shown to improve fish stress tolerance and immune activation for a certain period under stressful conditions or unchanged water, based on the stocking density, dosages of herbs used, and the extent of deterioration of the water quality.

Physical exercise halts further functional decline in an animal model for Charcot-Marie-Tooth disease 1X at an advanced disease stage.

Charcot-Marie-Tooth (CMT) type 1 neuropathies are the most common inherited diseases of the peripheral nervous system. Although more than 100 causative genes have been identified so far, therapeutic options are still missing. We could previously identify that early-onset physical exercise (voluntary wheel running, VWR) dampens peripheral nerve inflammation, improves neuropathological alterations, and clinical outcome in Cx32def mice, a model for CMT1X. We here investigate the clinical and histopathological effect of late-onset exercise in Cx32def mice at an advanced disease stage. Nine-month-old Cx32def mice were allowed to run for 4 days/week on a commercially available running wheel for 3 months, with timely limited access to running wheels, representing a running distance of ~2000 m. Control mutants had no access to running wheels. Afterward, mice were investigated by distinct functional tests and by immunohistochemical and electron microscopical techniques. We found that late-onset physical exercise (late VWRlim) prevented the robust functional decline in 12-month-old Cx32def mice. This was accompanied by improved neuromuscular innervation of distal muscles and axonal preservation in femoral quadriceps nerves. In contrast to a "pre-symptomatic" start of physical exercise in Cx32def mice, late-onset VWR did not alter nerve inflammation and myelin thickness at 12 months of age. We conclude that VWR has robust beneficial effects on nerve function in Cx32def mice, even when applied at a progressed disease stage. These results have important translational implications, suggesting that physical exercise might be an effective treatment option for CMT1 patients, even when disease symptoms have already progressed.

Synergistic effect of the sphingosine kinase inhibitor safingol in combination with 2'-nitroflavone in breast cancer.

Sphingosine kinase-1 (SPHK1), the enzyme that catalyzes the synthesis of the pro-oncogenic molecule sphingosine-1-phosphate, is commonly upregulated in breast cancer cells and has been linked with poor prognosis and progression by promoting cell transformation, proliferation, angiogenesis, and metastasis. Therefore, SPHK1-targeting drugs have been proposed for breast cancer treatment, with better antitumor results when they are combined with chemotherapy. Previously, we demonstrated that the synthetic flavonoid 2'-nitroflavone (2'NF) exerted a potent and selective antiproliferative effect in murine HER2-positive LM3 mammary tumor cells. As we found that these cells overexpress SPHK1, we decided to explore the antitumor action of the combination of SPHK inhibitors (safingol or SKI-II) with 2'NF. In vitro assays showed that the combination induced a synergistic antiproliferative effect in LM3 cells. Similar results were obtained when human HER2-positive MDA-MB-453 breast cancer cells were treated with the combination of 2'NF/safingol. We also found that safingol potentiated the 2'NF apoptotic effect in both cell lines. The synergistic antitumor effect was confirmed in vivo in an LM3 syngeneic breast cancer model. Moreover, western blot analysis of tumor lysates revealed that combined treatment increased PARP cleavage and Bax protein levels and decreased anti-apoptotic Bcl-xL and Bcl-2 protein levels. Additionally, mice treated with both compounds showed no histopathological effects on different organ tissues. In summary, these findings suggest that the combination safingol/2'NF can be proposed as a potential therapeutic strategy for HER2-positive breast cancer treatment. KEY MESSAGES: The combination safingol/2'-nitroflavone exerts a synergic antitumor action in vitro. Safingol potentiates 2'-nitroflavone apoptotic effect in breast cancer cells. Safingol enhances the 2'-nitroflavone antitumor activity in vivo in breast cancer.

The Effect of Rosuvastatin on Facial Nerve Regeneration After Facial Nerve Injury: An Experimental Animal Study.

Rosuvastatin is an antihyperlipidemic statin group pharmacological agent with antioxidant, neuroprotective, and anti-inflammatory effects. In this study, we aimed to examine the functional, electrophysiological, and histopathological effects of rosuvastatin or in combination with corticosteroids on facial nerve regeneration in rats with traumatic peripheral facial paralysis (PFP). PFP was induced in 28 female Sprague Dawley rats that we divided into 4 groups: group 1, control group; group 2, methylprednisolone group; group 3, rosuvastatin group; group 4, rosuvastatin and methylprednisolone group. Electrophysiological, functional, and histopathological examinations were performed before and after the medications. Electrophysiological threshold values of group 3 and group 4 were found to be significantly lower than the control group on day 21 after treatment (P = .002, P = .001; P < .01).In the histopathological evaluation, axonal degeneration, macrovacuolization, and vascular congestion levels were compared between the groups, and a statistically significant difference was observed in group 4 compared to the control group. The recovery time of the eye corneal reflex was found to be significantly higher in the control group than in groups 3 and 4 when comparing postoperative day 1 to day 7 and postoperative day 1 to day 14. Rosuvastatin, especially when combined with methylprednisolone was found to significantly increase the facial nerve electrophysiological, functional, and histopathological recovery in injury-induced traumatic PFP.

The effects of tranexamic acid on the histopathology of defect healing in an in vivo porcine model after gastric and colonic endoscopic submucosal dissection.

There is limited data on the histopathological effects of hemostatic agents (HAs) used during endoscopic submucosal dissection (ESD). We used an in vivo porcine model to compare the tissue effects of tranexamic acid (TXA) and adrenaline (epinephrine) compared to controls. Standard ESD, using a 2 mm flash-knife, was performed in three pigs. Four resections were performed in the stomach and rectum of each pig. Injectate contained 4% succinylated gelatin solution and indigo carmine, plus either TXA, adrenaline, or neither. Pigs were euthanized after 7 days and evaluated by two blinded pathologists. Twenty-four defects were analyzed. Within each animal no significant histopathological changes were noted between the defects, but differences were noted between the animals. In the stomachs of the TXA and adrenaline pigs, pathology revealed a clear ulcer in the mucosa/submucosa with abundant granulation tissue, while the muscular layer was unaffected. In the control pig's stomach, the lesions were deeper, transmurally distributed, with inflammation of the muscular and adventitia layers accompanied by severe inflammation and necrosis. Fewer differences were noted in the rectum. For ESD, HAs such as TXA and adrenaline may have protective effects on the depth and extent of injury to the underlying tissue.

Biochemical and Histopathological Analysis of Aqueous Extract of an Aphrodisiac Formulation against Acetaminophen Induce Hepatocyte Injuries in Wistar Rats

The aimed of this study was to examine the biochemical parameters and histopathological effects of aqueous extract of an aphrodisiac formulation against acetaminophen induce hepatocyte injuries in Wistar rats. Zainacin Dadin duniya (aphrodisiac herbs) extract was prepared by cold maceration. The animal study was done using 30 adult both male and female Wistar rats was grouped into 5 groups (n=6) and orally administered with five different treatments (saline, liver drug, acetaminophen, extract and extract/ acetaminophen) for the period of 28days. The blood is collected from each grouped rat for biochemical parameters test and all rats were later sacrificed for histologically processed investigation. The results showed that the oral administration of the acetaminophen in group 3 treated rats causes a significant (P&lt;0.05) increased in the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), but, when administered with the extract in group 4 rats, there was a significantly (p&lt;0.05) decreased in the activities of ALT, AST and ALP. Significantly (p&lt;0.05) increased in the Kidney Function Markers (Creatinine, and Urea) and decreased in Glucose level in the group 3 rats treated with acetaminophen, when compared with the group 4 rats treated with the extract, there was a significant (p&lt;0.05) decreased in Creatinine, and Urea level and increased in the Glucose level. The serum total protein, Albumin, and Globulin significantly (p&lt;0.05) decreased in the group 3 rats treated with acetaminophen while the bilirubin increased significantly. While group 4 rats showed significant increase in the total protein, Albumin, and Globulin and decreased in the bilirubin levels. The Results of Histopathology findings revealed hepatic tissue with distorted hepatocytes, portal vein, and sinusoids accompanied with massive necrosis in the liver of the group 3 rats treated with acetaminophen. While the liver of the group 4 rats showed, hepatic tissue with preserved architecture composed of cords of normal hepatocytes, normal portal vein, and sinusoids. There are no features of acute or chronic damage. The histologically Results of the small intestines of the all five (5) grouped rats showed preserved layers of muscosa, submucosa, muscularis externa, and serosa. There are no features of acute or chronic toxicity. Conclusively, the prolonged oral consumption of acetaminophen in animals resulted in hepatocellular deleterious effects and may be of a similar hazard in humans. Overall, administration of the extract in rats has significant ameliorative effect on the rats; this may be of immense benefits in the management of hepatocytes, necrosis in the liver and its associated biomarkers complications. Improved liver functions as well as improved antioxidant status are beneficial in the management of chronic diseases such as liver failure.

Salinity influence on Mytilus galloprovincialis exposed to antineoplastic agents: a transcriptomic, biochemical, and histopathological approach

Nowadays, aquatic species face a variety of environmental risks associated with pharmaceutical consumption. More specifically, the increased number of cancer patients has been accompanied by an increased consumption of antineoplastic drugs, such as ifosfamide (IF) and cyclophosphamide (CP). These drugs have been found in aquatic ecosystems, raising concerns about their impact, especially on estuarine species, as marine waters are the final recipients of continental effluents. Simultaneously, predicted climatic changes, such as salinity shifts, may threaten organisms. Considering this, the present research aims to investigate the combined effects of IF and CP, and salinity shifts. For this, a transcriptomic, biochemical, and histopathological assessment was made using the bivalve species Mytilus galloprovincialis exposed for 28 days to IF and CP (500 ng/L), individually, at different salinity levels (20, 30, and 40). IF and CP up-regulated metabolism-related gene cyp3a1, with CP also affecting abcc gene, showing minimal salinity impact and highlighting the importance of these metabolic routes in mussels. Salinity shifts affected the transcription of genes related to apoptosis and cell cycle growth, such as p53, as well as the aerobic metabolism, the antioxidant and biotransformation mechanisms. These findings indicate mussels' high metabolic adaptability to osmotic stress. Under CP exposure and low salinity, mussels exhibited increased cellular damage and histopathological effects in digestive gland tubules, revealing detrimental effects towards M. galloprovincialis, and suggesting that a metabolic slowdown and activation of antioxidant mechanisms helped prevent oxidative damage at the control and high salinities. Overall, results reinforce the need for antineoplastics ecotoxicological risk assessment, especially under foreseen climate change scenarios.

Behaviour, biochemical and histological responses of the freshwater mussels Unio ravoisieri exposed to wastewater from Wadi Guenniche (Northeastern Tunisia)

ABSTRACT Wastewater effluents increase contaminant levels in the aquatic environment, leading to various disruptive effects. In this study, responses of Unio ravoisieri transplanted into wastewater from Wadi Guenniche were monitored using filtration rate, oxidative stress, lipo-peroxidation, neurotoxicity and histopathological markers. The filtration rate was significantly increased by exposure to diluted wastewater, rising from 35.13 mg indiv−1 h−1 in the control to 63.49 mg indiv−1 h−1 in the mussels after 96 h of exposure. In contrast, this exposure significantly reduces catalase, glutathione-S-transferase and acetylcholinesterase activities in both organs. This decrease is dependent on the effluent concentration and time exposure. The malondihaldehyde content showed an increasing profile in both organs. It is only in the gills that this increase is significant for mussels transplanted in situ for 48 h. Contamination by wastewater causes histopathological changes in both organs, marked by infiltration, vacuolisation, secretion of lipofuscins and cell necrosis. The intensity of these lesions depends on the duration of exposure and the degree of pollution. The mean incidence of lesions increases depending on effluent concentration and exposure time in both organs. Our study contributes to the database on behavioural, biochemical and histopathological effects in mussels following the discharge of wastewater effluent into a freshwater ecosystem.

Protective effect of essential oil of Foeniculum vulgare Mill. against bleomycin-induced pulmonary fibrosis and oxidative stress in rat

BackgroundWild fennel (Foeniculum vulgare Mill.) is a very common plant used in traditional medicine to treat several diseases. In recent years, scientific research proved its biological properties. However, the protective effect of fennel against bleomycin-induced pulmonary fibrosis (BLM-IPF) is not yet study. PurposeFennel essential oil (FEO) composition was characterized and its protective effect was assessed. MethodsGC–MS was employed to determine the chemical composition of fennel essential oil. The antioxidant activity was evaluated using TAC, DPPH, RAP and ABTS assays. After inducing fibrosis by bleomycin, several biological assays were used to evaluate the protective effect [proteins content, malondialdehyde MD, thiol group, superoxide dismutase (SOD) and catalase (CAT)]. ResultsFEO was rich in estragole (77.55 %), fenchone (9.23 %), and limonene (9.23 %), and phenolic compounds and showed a significant antioxidant potential. The effects on BLM-IPF were revealed by disruption and alteration of oxidative stress biomarkers in lung, liver and kidney. Treatment of rats with FEO improved abnormal fluctuations in protein and thiol levels, decreased oxidative stress in terms of MDA and also restored the response of the antioxidant system, measured in terms of SOD and CAT, in lung, liver and kidney. The biological activity was recorded in a dose response manner. The potential of FEO in limiting the progress of the histopathologic effects of BLM-IPF was confirmed by microscopic histological observations, with a reduction of the fibrosis score and the inflammatory index in the FEO treated lung tissue. ConclusionThese results, proved that FEO could attenuate BLM-induced PF, thus suggesting that the latter could serve as a potential therapeutic approach for PF.

In ovo toxico-pathological effects of medicinal plants used against coccidiosis on chicken embryos development and hatchability

TOXICO-pathological effects of herbal plants have always been a major concern, but little information is provided on the toxico-pathological effects of medicinal plants used against coccidiosis. This study aimed to assess the histopathological effects of Carica papaya seeds (CPS), Azadirachta indica leaves (AIL), and Sarcocephalus latifolius root (SLR) used as coccidiostat in traditional poultry farms with various doses using the chick embryo model. A total of 420 Sasso breeder eggs at ED4 of incubation were inoculated with the extract of these plants following a 3×4 factorial design with 3 plant extracts (CPS, AIL and SLR) and 4 inoculation doses (0, 25, 50 and 100 mg/kg egg-weight). From ED6 to ED19, the weights of the albumen and embryo were recorded, and the weights of ED19 embryo organs such as liver, heart, kidney, and lungs were measured. Additionally, histopathological lesions were examined. The results indicated that the presence of various phytoconstituents such as alkaloids, phenolics, flavonoids, tannins, saponins, coumarins, steroids, and triterpenes with statistically significant free-radical-scavenging ability differed among the plant extracts (p < 0.0001). Toxico-pathological examination revealed a dose-dependent slight toxicity (p < 0.0001) of the Azadirachta indica leaves extract compared to the other plants. Additionally, the relative organ weight showed kidney hypertrophy (p = 0.001) and liver hypertrophy (p = 0.0001), as well as dilation of hepatic and cardiac vessels. The conclusion drawn was that chicken embryos are more susceptible to in ovo inoculation with Azadirachta indica leaves compared to Carica papaya seeds and Sarcocephalus latifolius root.

Can intra-articular daidzein injection reduce oxidative damage and early osteoarthritis in a rabbit temporomandibular joint model?

BackgroundOxidative damage and inflammatory cytokines in osteoarthritis (OA) exacerbate the disease course. Daidzein (DZ) has antioxidant and anti-inflammatory effects. This study evaluated the early histopathological effects of intra-articular daidzein injection on experimentally induced osteoarthritis in rabbit TMJs.MethodsThe predictor variable was intra-articular injection of DZ or a saline control. 50 µl of 3 mg/mL MIA solution was injected into the right TMJ of 16 New Zealand rabbits to induce experimental OA. One rabbit was sacrificed after 4 weeks to confirm the formation of the OA model and the OA model was obtained. The remaining 15 rabbits were randomly divided into 2 groups: an experimental group (9 rabbits) and a control group (6 rabbits). On days 1, 7, 14, and 21; 50 µl of saline solution was applied to the right TMJ of the control group and 50 µl daidzein solution (1.8 mg/ml) was applied to the right TMJ to the experimental group. After one week from the date of the last injection, the rabbits were sacrificed, and histopathological and biochemical evaluations were performed. The Shapiro-Wilk test was used to evaluate whether the variables in the study conformed to normal distribution. Mean ± SD (standard deviation) or median (interquartile range (IQR)) was used to show the descriptive statistics of the variables. T-test and Mann Whitney U test were used to compare the control and experimental groups for biochemical changes. The chi-square test was used to show the distribution of histopathological changes variables obtained within the scope of the study based on control and experimental groups. A P-value < 0.05 was considered significant for all evaluations.ResultsThere were 8 and 6 animate treated with DZ and saline, respectively. There was no statistically significant difference between groups in articular cartilage (p = 0.3), osteochondral junction (p = 0.3), subchondral bone structure (p = 1.0) or chondrocyte appearance (p = 0.4). The experimental group showed significantly lower mean values for Total Oxidant Status (TOS) (p = 0.002) and Oxidative Stress Index (OSI) (p = 0.007).ConclusionsAn intra-articular DZ injection appears to show limited reduction of oxidative damage and early OA in the rabbit TMJ. DZ might represent a promising natural compound with beneficial effects in the management of TMJ-OA.

Biochemical and Histopathological Effects of Olive Oil on The Small Intestine Injury Induced by Tartrazine in Iraqi Local Male Rabbits

Biochemical and Histopathological Effects of Olive Oil on The Small Intestine Injury Induced by Tartrazine in Iraqi Local Male Rabbits

Histological assessment of the effect of 50mW red laser on retina at variable time intervals: animal model.

To assess the histopathological effect of 50milliWatt red laser pointer on mice retinal tissue at variable exposure times. The experimental study was conducted in the Postgraduate Laboratory of the Unit of Medical Physics, Department of Physiology, College of Medicine, Mustansiriyah University, Baghdad, Iraq, from November 2020 to April 2021, and comprised albino mice. Histopathological effects on the retinal tissues were evaluated microscopically using conventional haematoxylin and eosin stain just after being exposed to commercially available 50 milliWatt red laser pointers with 630nm wavelength at 1, 2 and 3 minutes, grouped as R1, R2 and R3, respectively. The laser beam was focussed on the right eye of the mice sedated with sodium pentobarbital, reserving the left eye for use as a control group. Data was analysed using SPSS 24. Of the 12 mice, 4(33.3%) were in each of the 3 groups. There was significantly destructive effect of red laser on retinal outer cellular layers in all the groups compared to the controls (p<0.05). The effect was significant between R1 and R2 (p=0.0001), and between R2 and R3 (p=0.02). The handheld commercial red laser pointers could harmfully affect a wide range of mice retina and choroid.

Does Radiofrequency Radiation From Mobile Phones Affect the Formation of Parotid Gland Malignancy? An Experimental Study.

Objectives: The use of mobile phone is increasing around the world. Although it is beneficial in terms of communication, the electromagnetic radiations emitted by mobile phones may cause undesirable biological effects on the human body. In practical use, the tissue with which mobile phones come into most and are closest is the parotid gland. This study investigated the effects of the 1800 MHz electromagnetic field created by a generator on the parotid gland in rats. Methods: A total of 21 Sprague-Dawley Albino rats were included in the study. The rats were randomly divided into three equal groups. To simulate a mobile phone in conversation mode, the first study group was exposed to an 1800-MHz electromagnetic field for 6 hours a day for 30 days, and the second study group was exposed to an 1800-MHz electromagnetic field for 12 hours a day for 30 days. After 30 days, rats were sacrificed, and histopathological and immunohistochemical methods were used to evaluate the effects on the parotid gland. The total antioxidant level and the total oxidant level were measured biochemically in homogenized parotid tissue. Results: Histopathological results showed an increase in degeneration in rats exposed to electromagnetic fields for 6 and 12 hours a day, and immunohistochemical analysis showed an increase in the apoptotic index in both study groups (P = .001, P < .001). Intranuclear inclusions was observed during histopathological examination performed by electron microscopy. Conclusions: This study observed that the 1800 MHz electromagnetic field caused undesirable adverse histopathological and biochemical effects on the parotid gland of rats. Histopathological and biochemical findings were detected with increasing contact and exposure time. This study will lead to other studies on this topic and contribute to the literature by completing other studies.

Identification and preclinical evaluation of MMV676558 as a promising therapeutic candidate against Clostridioides difficile

Clostridioides difficile, a gram-positive, toxin-producing, spore-forming anaerobe, is a major cause of antibiotic-associated diarrhoea. The bacterium's intrinsic drug resistance limits current treatment options to fidaxomicin and vancomycin for initial episodes, with anti-toxin B monoclonal antibody or faecal microbiota transplantation recommended for complicated or recurrent cases. This underscores the urgent need for novel therapeutics. In this study, we screened the MMV Pathogen Box at a 10 µM concentration against C. difficile R20291. Primary hits were evaluated for minimum inhibitory concentrations (MIC), killing kinetics, and biofilm inhibition. Bacterial cytological profiling (BCP) and transmission electron microscopy (TEM) were employed to study the mode of action. MMV676558 was further tested in a mouse model to assess survival, histopathology, and gut microbiota effects. We identified nineteen hits that inhibited over 50 % of C. difficile growth. MIC assays revealed three hits with MICs below 16 µg/mL: MMV676558, MMV688755, and MMV690027. These hits were effective against various C. difficile ribotypes. Killing kinetics were comparable or superior to vancomycin and fidaxomicin, and biofilm assays showed inhibitory effects. BCP and TEM analyses suggested membrane function disruption as the mode of action. Furthermore, MMV676558 demonstrated a protective effect in mice, with favourable histopathology and gut microbiota profiles. Given the urgent threat posed by C. difficile antibiotic resistance, discovering new treatments is a top priority. Our study identified three promising hits from the MMV Pathogen Box, with MMV676558 showing significant in vivo potential for further evaluation.