Investigation of the miRNA levels changes to acceptable daily intake dose pesticide mixture exposure on rat mesentery and pancreas.

Consumers are constantly exposed to a variety of chemical mixtures as part of their everyday activities and lifestyle. Food, water and commercial products are only some examples of the possible ways people get exposed to these mixtures. However, following federal and local guidelines for risk assessment related to chemical exposure, risk analysis focuses on a single substance exposure scenario and not on a mixture, as in real life. Realizing the pronounced gap of this methodology, the real-life risk simulation scenario approach tries to address this problem by investigating the possible effect of long-term exposure to chemical mixtures closely resembling the actual circumstances of modern life. As part of this effort, this study aimed to identify the cumulative effects of pesticides belonging to different classes and commonly used commercial products on long-term exposure with realistic doses. Sprague Dawley rats were given a pesticide mix of active ingredients and formulation chemicals in a daily acceptable dose (ADI) and 10xADI for 90 days. Following thorough everyday documentation of possible side-effects, after 90 days all animals were sacrificed and their organs were examined. Exposure to pesticides particularly affects the miRNA levels at that point will provide us with more information about whether they can be potential biomarkers.

Assessment of antimicrobial activity and In Vitro wound healing potential of ZnO nanoparticles synthesized with Capparis spinosa extract.

Agents that will accelerate wound healing maintain their clinical importance in all aspects. The aim of this study is to determine the antimicrobial activity of zinc oxide nanoparticles (ZnO NPs) ZnO nanoparticles obtained by green synthesis from Capparis spinosa L. extract and their effect on in vitro wound healing. ZnO NPs were synthesized and characterized using Capparis spinosa L. extract. ZnO NPs were tested against nine ATCC-coded pathogen strains to determine antimicrobial activity. The effects of different doses (0.0390625-20 µg/mL) of NPs on cell viability were determined by MTT assay. The effect of ZnO NPs doses (0.0390625 µg/mL, 0.078125 µg/mL, 0.15625 µg/mL, 0.3125 µg/mL, 0.625 µg/mL, 1.25 µg/mL) that increase proliferation and migration on wound healing was investigated in an in vitro wound experiment. Cell culture medium obtained from the in vitro wound assay was used for biochemical analysis, and plate alcohol-fixed cells were used for immunohistochemical staining. It was determined that NPs formed an inhibition zone against the tested Gram-positive bacteria. The ZnO NPs doses determined in the MTT test provided faster wound closure in in-vitro conditions compared to the DMSO group. Biochemical analyses showed that inflammation and oxidative status decreased, while antioxidant levels increased in ZnO NPs groups. Immunohistochemical analyses showed increased expression levels of Bek/FGFR2, IGF, and TGF-ß associated with wound healing. The findings reveal the antimicrobial effect of ZnO nanoparticles obtained using Capparis spinosa L. extract in vitro and their potential applications in wound healing.

Evaluated periodontal tissues and oxidative stress in rats with neuropathic pain-like behavior.

BACKGROUND: Oxidative stress has a critical effect on both persistent pain states and periodontal disease. Voltage-gated sodium NaV1.7 (SCN9A), and transient receptor potential ankyrin 1 (TRPA1) are pain genes. The goal of this study was to investigate oxidative stress markers, periodontal status, SCN9A, and TRPA1 channel expression in periodontal tissues of rats with paclitaxel-induced neuropathic pain-like behavior (NPLB). METHODS AND RESULTS: Totally 16 male Sprague Dawley rats were used: control (n = 8) and paclitaxel-induced pain (PTX) (n = 8). The alveolar bone loss and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were analyzed histometrically and immunohistochemically. Gingival superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities (spectrophotometric assay) were measured. The relative TRPA1 and SCN9A genes expression levels were evaluated using quantitative real-time PCR (qPCR) in the tissues of gingiva and brain. The PTX group had significantly higher alveolar bone loss and 8-OHdG compared to the control. The PTX group had significantly lower gingival SOD, GPx and CAT activity than the control groups. The PTX group had significantly higher relative gene expression of SCN9A (p = 0.0002) and TRPA1 (p = 0.0002) than the control in gingival tissues. Increased nociceptive susceptibility may affect the increase in oxidative stress and periodontal destruction. CONCLUSIONS: Chronic pain conditions may increase TRPA1 and SCN9A gene expression in the periodontium. The data of the current study may help develop novel approaches both to maintain periodontal health and alleviate pain in patients suffering from orofacial pain.

The melatonin agonist ramelteon attenuates bleomycin-induced lung fibrosis by suppressing the NLRP3/TGF-Β1/HMGB1 signaling pathway.

PURPOSE: The possible effects of ramelteon, a melatonin receptor agonist on bleomycin-induced lung fibrosis were analyzed via transforming growth factor ß1 (TGF-ß1), the high mobility group box 1 (HMGB1) and Nod-like receptor pyrin domain-containing 3 (NLRP3) which are related to the fibrosis process. MATERIALS AND METHODS: Bleomycin (0.1 â€‹mL of 5 â€‹mg/kg) was administered by intratracheal instillation to induce pulmonary fibrosis (PF). Starting 24 â€‹h after bleomycin administration, a single dose of ramelteon was administered by oral gavage to the healthy groups, i.e. PF â€‹+ â€‹RM2 (pulmonary fibrosis model with bleomycin â€‹+ â€‹ramelteon at 2 â€‹mg/kg) and PF â€‹+ â€‹RM4 (pulmonary fibrosis model with bleomycin â€‹+ â€‹ramelteon at 4 â€‹mg/kg) at 2 and 4 â€‹mg/kg doses, respectively. Real-time polymerase chain reaction (real-time PCR) analyses, histopathological, and immunohistochemical staining were performed on lung tissues. Lung tomography images of the rats were also examined. RESULTS: The levels of TGF-ß1, HMGB1, NLRP3, and interleukin 1 beta (IL-1ß) mRNA expressions increased as a result of PF and subsequently decreased with both ramelteon doses (p â€‹< â€‹0.0001). Both doses of ramelteon partially ameliorated the reduction in the peribronchovascular thickening, ground-glass appearances, and reticulations, and the loss of lung volume. CONCLUSIONS: The severity of fibrosis decreased with ramelteon application. These effects of ramelteon may be associated with NLRP3 inflammation cascade.

Comparison of three different dosages of low-level laser therapy on expression of cell proliferation and inflammatory markers following ovariohysterectomy in rats.

The objective of the current study was to evaluate Low-level laser therapy (LLLT) on the healing of incisional wounds following ovariohysterectomy in rats, by means of subjective histopathological and immunohistochemical analysis. A total of 72 female Wistar rats were categorised into four treatment groups (Group I; sacrification 4 hours following only one LLLT application, Group II; sacrification 7 days following only one LLLT application, Group III; sacrification 4 hours after two LLLT applications, and Group IV; sacrification 7 days after two LLLT applications). Each group was further divided into four different doses subgroups (Group Control [C, off mode LLLT application], L1 [1 J/cm2], L3 [3 J/cm2], and L6 [6 J/cm2]), with equal representation in each subgroup. Ovariohysterectomy was employed using two 2-cm-length midline abdominal incisions in the left and right sides of line alba. The Group C was assigned to the left side incision to each rat in the study. After irradiation, the tissue was subjected to histopathological analysis to determine the extent of mononuclear cell infiltration, edoema, and epithelialization. Additionally, immunohistochemical analysis was performed to evaluate the expression of proliferating cell nuclear antigen (pCNA) and inducible nitric oxide synthase (iNOS). Group L1 and L3 significantly decreased mononuclear cell infiltration compared with Group C in all treatment groups (p < 0.05). Group L3 significantly decreased edoema compared with Group C in all groups except for treatment Group I (p < 0.05). Group L2 and L3 significantly increased epithelization in treatment Group IV (p < 0.05). Moreover, Group L2 and L3 significantly increased pCNA in all groups, while L2 and L3 significantly decreased iNOS expression in treatment Group II, III, and IV (p < 0.05). However, no statistical difference was found between subgroups of treatment Group I in iNOS expiration (p > 0.05). The results of the current examination demonstrated that LLLT can modulate mononuclear cell infiltration and edoema, and improve epithelization, as well as increase pCNA expression, whereas decrease iNOS expression during the wound healing process, therefore enhancing wound healing following ovariohysterectomy in rats.

The effects of low-level laser therapy on polycystic ovarian syndrome in rats: three different dosages.

The main objective of this in vivo study was to investigate the effect of different low-level laser therapy (LLLT) doses on polycystic ovary syndrome (PCOS). In the present experimental study, a single dosage of estradiol valerate (EV) was administered to induce PCOS in female rats. After administration of the EV for induction of PCOS, rats were divided into 5 groups (n = 8/group): C group (animals that were not exposed to any form of procedure), PC group (no treatment following EV induction), L1 group (1 J/cm2 LLLT treatment following EV induction), L2 group (2 J/cm2 LLLT treatment following EV induction), L3 group (6 J/cm2 LLLT treatment following EV induction). The results indicated that no significant difference was found in the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and progesterone (P4) between the C and L2 groups (p < 0.05). Although the serum levels of testosterone (T) were significantly higher in the C group compared with other groups (p < 0.05), the L2 group was determined to be the closest to the C group. Additionally, the LH, FSH, and T receptor level of the L2 group was closest to the C group. In conclusion, a 2 J/cm2 dosage of LLLT (L2 group) can be considered the most potentially effective treatment of PCOS in the rat. However, more studies are needed to determine the optimal dose of LLLT for the treatment of PCOS.

FGF-18 alleviates memory impairments and neuropathological changes in a rat model of Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial pathology marked by amyloid beta (Aß) accumulation, tau hyperphosphorylation, and progressive cognitive decline. Previous studies show that fibroblast growth factor 18 (FGF18) exerts a neuroprotective effect in experimental models of neurodegeneration; however, how it affects AD pathology remains unknown. This study aimed to ascertain the impact of FGF18 on the behavioral and neuropathological changes in the rat model of sporadic AD induced by intracerebroventricular (ICV) injection of streptozotocin (STZ). The rats were treated with FGF18 (0.94 and 1.88 pmol, ICV) on the 15th day after STZ injection. Their cognitive function was assessed in the Morris water maze and passive avoidance tests for 5 days from the 16th to the 21st days. Aß levels and histological signs of neurotoxicity were detected using the enzyme-linked immunosorbent assay (ELISA) assay and histopathological analysis of the brain, respectively. FGF18 mildly ameliorated the STZ-induced cognitive impairment; the Aß accumulation was reduced; and the neuronal damage including pyknosis and apoptosis was alleviated in the rat brain. This study highlights the promising therapeutic potential for FGF18 in managing AD.

Parthenolide as a potential analgesic in the treatment of paclitaxel-induced neuropathic pain: the rat modeling.

In this study, we determined the therapeutic effect of parthenolide (PTL), the active component of Tanacetum parthenium, on neuropathic pain caused by paclitaxel (PTX), a chemotherapeutic drug frequently used in cancer treatment, at the gene and protein levels. To this end, 6 groups were formed: control, PTX, sham, 1 mg/PTL, 2 mg/kg PTL, and 4 mg/kg PTL. Pain formation was tested by Randall-Selitto analgesiometry and locomotor activity behavioral analysis. Then, PTL treatment was performed for 14 days. After the last dose of PTL was taken, Hcn2, Trpa1, Scn9a, and Kcns1 gene expressions were measured in rat brain (cerebral cortex/CTX) tissues. In addition, changes in the levels of SCN9A and KCNS1 proteins were determined by immunohistochemical analysis. Histopathological hematoxylin-eosin staining was also performed to investigate the effect of PTL in treating tissue damage on neuropathic pain caused by PTX treatment. When the obtained data were analyzed, pain threshold and locomotor activity decreased in PTX and sham groups and increased with PTL treatment. In addition, it was observed that the expression of the Hcn2, Trpa1, and Scn9a genes decreased while the Kcns1 gene expression increased. When protein levels were examined, it was determined that SCN9A protein expression decreased and the KCNS1 protein level increased. It was determined that PTL treatment also improved PTX-induced tissue damage. The results of this study demonstrate that non-opioid PTL is an effective therapeutic agent in the treatment of chemotherapy-induced neuropathic pain, especially when used at a dose of 4 mg/kg acting on sodium and potassium channels.

Chlorogenic Acid Attenuates Doxorubicin-Induced Oxidative Stress and Markers of Apoptosis in Cardiomyocytes via Nrf2/HO-1 and Dityrosine Signaling.

(1) Background: Doxorubicin (DOX) is extensively used for cancer treatments; however, its clinical application is limited because of its cardiotoxic adverse effects. A combination of DOX and agents with cardioprotective properties is an effective strategy to ameliorate DOX-related cardiotoxicity. Polyphenolic compounds are ideal for the investigation of novel cardioprotective agents. Chlorogenic acid (CGA), an essential dietary polyphenol found in plants, has been previously reported to exert antioxidant, cardioprotective, and antiapoptotic properties. The current research evaluated CGA's in vivo cardioprotective properties in DOX-induced cardiotoxicity and the probable mechanisms underlying this protection. (2) Methods: CGA's cardioprotective properties were investigated in rats that were treated with CGA (100 mg/kg, p.o.) for fourteen days. The experimental model of cardiotoxicity was induced with a single intraperitoneal (15 mg/kg i.p.) injection of DOX on the 10th day. (3) Results: Treatment with CGA significantly improved the DOX-caused altered cardiac damage markers (LDH, CK-MB, and cTn-T), and a marked improvement in cardiac histopathological features accompanied this. DOX downregulated the expression of Nrf2/HO-1 signaling pathways, and the CGA reversed this effect. Consistently, caspase-3, an apoptotic-related marker, and dityrosine expression were suppressed, while Nrf2 and HO-1 expressions were elevated in the cardiac tissues of DOX-treated rats after treatment with the CGA. Furthermore, the recovery was confirmed by the downregulation of 8-OHdG and dityrosine (DT) expressions in immunohistochemical findings. (4) Conclusions: CGA demonstrated a considerable cardioprotective effect against DOX-induced cardiotoxicity. One of the possible mechanisms for these protective properties was the upregulation of the Nrf2/HO-1-dependent pathway and the downregulation of DT, which may ameliorate oxidative stress and cardiomyocyte apoptosis. These findings suggest that CGA may be cardioprotective, particularly in patients receiving DOX-based chemotherapy.

Anticancer activity of lycopene in HT-29 colon cancer cell line.

An inverse association between serum lycopene levels and the risk of cancers has been pointed out by many prospective and retrospective epidemiological studies which prompted more studies to be performed on animal models and cell cultures in order to test this hypothesis. The aim of the present study was to evaluate the antiproliferative and pro-apoptotic effect of lycopene on colon cancer HT-29 cell line. The effect of lycopene on the viability of HT-29 cell line was investigated using XTT assay. The levels of Bcl-2, cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG in lycopene-treated HT-29 cells were measured using ELISA. Gamma-H2AX and cytochrome c expression was assessed semi-quantitatively using immunofluorescence staining. Lycopene at doses of 10 and 20 µM produced a significant antiproliferative effect on HT-29 cells compared to the control (p < 0.05). The IC50 value of lycopene in HT-29 cells was found to be 7.89 µM for 24 h. Lycopene (7.89 µM) significantly elevated cleaved caspase 3 (p < 0.01), BAX, and cleaved PARP, 8-oxo-dG levels (p < 0.05). The levels of γ-H2AX foci are significantly higher while the levels of cytochrome-c are lower (p < 0.05) in lycopene-treated HT-29 cells. These results indicate that lycopene has an antiproliferative apoptotic and genotoxic effect on HT-29 colon cancer cell line.

Deteriorated Vascular Homeostasis in Hypertension: Experimental Evidence from Aorta, Brain, and Pancreatic Vasculature.

Hypertension, as a primary risk factor for many fatal disorders, is prevalent in the elderly. There is wide literature on hypertension dealing with its biological and/or biochemical aspects; however, limited research is available on the multifactorial nature of hypertension from a mechanobiological standpoint. This study intended to study in parallel histopathological alterations and deviated protein expressions with the mechanical behavior of the hypertensive tissues. The Goldblatt (2K1C) method was chosen for induction of renovascular hypertension in rabbits. The microstructural and immunohistological characteristics of the aortic, pancreatic, and brain vasculature were investigated. The mechanical properties of the aortic tissue were also evaluated using biaxial tensile tests. Our findings indicated severe hypertrophy of the hypertensive vessels and declined content of intact smooth muscle cells. Most of the collagen I content of the wall was compromised and less functional type III collagen was highly expressed. Reversed collagen I to collagen III ratio was the main contributor to the hypertrophic and less stiff hypertensive vessel walls. The multifactorial nature of hypertension is illustrated, and smooth muscle cell detachment is identified as the sign of described degenerative cascades all along the arterial tree.

Galium aparine L. protects against acetaminophen-induced hepatotoxicity in rats.

The toxicity of acetaminophen (N-acetyl-para-aminophenol (APAP)) is the most frequent cause of drug-induced liver damage. Galium aparine L. (GA) is traditionally used to treat jaundice. We aimed to investigate the hepatoprotective potential of GA in the APAP-induced hepatic encephalopathy (HE) rat model. Qualitative phytochemical characterization of GA was performed by LC/Q-TOF/MS analysis. Wistar rats were pretreated with GA (250 and 500 mg/kg b.wt. per oral) for five days. On the 6th day, the rats were exposed to APAP (1500 mg/kg b.wt. oral gavage) and behavioral tests (open field and passive avoidance tests) were applied on the 7th and 8th days. The animals were killed, and biochemical and histopathological parameters were assessed in blood and hepatic specimens. GA pretreated rats exhibited a significant reduction in APAP-induced liver damage, evidenced by the reduction in liver necrosis and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin (BIL). GA demonstrated an anxiolytic effect, as seen in the acquisition trial and grooming behavior. The short-term memory performances of animals were not changed in all groups, suggesting that APAP intoxication did not affect hippocampal function. These results show that GA extract markedly exerts hepatoprotective activity, while its effect on hepatic encephalopathy was limited.

Increased nociceptive sensitivity is associated with periodontal inflammation and expression of chronic pain genes in gingival tissues of male rats.

OBJECTIVE: This study aimed to evaluate the inflammatory response, hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2), and voltage-gated potassium (Kv) 9.1 channel expression in rats with paclitaxel-induced neuropathic pain-like behavior. METHODS: Sixteen male Sprague Dawley rats were divided equally into two groups: control and paclitaxel-induced pain (PTX). The attachment loss and inflammatory cell infiltrate levels were analyzed histometrically and immunohistochemically. The gene expression of HCN2 and KCNS1 was analyzed by qPCR in the brain and gingival tissues. RESULTS: The attachment loss and prominent infiltration of inflammatory cells were significantly higher in the PTX group than in the control groups. In gingival tissues; the expression levels of HCN2 (p = 0,0011) were significantly higher and KCNS1 (p = 0,0003) were significantly lower in the PTX group than in the control groups. CONCLUSION: Increased nociceptive sensitivity, may play a role in periodontal inflammation. KCNS1 may decrease and HCN2 expression may increase in periodontium in permanent chronic pain states. The results of the present study may be helpful in developing new approaches to alleviate pain and maintain periodontal health in patients suffering from orofacial pain.

Hepatoprotective and neuroprotective effect of taxifolin on hepatic encephalopathy in rats.

This study was planned to assess the potential protective effects of taxifolin against thioacetamide-induced hepatic encephalopathy and subsequently to portray its behavioural results. The experimental model was induced with three doses of (200 mg/kg i.p.) thioacetamide and taxifolin (50 and 100 mg/kg, p.o.) was administered for fourteen days. Taxifolin effectively attenuated hepatic encephalopathy through decrease in AST, ALT, ALP and LDH concentrations and improvement of hyperammonemia, and increase in antioxidant capacity by decreasing MDA, ROS, and increasing CAT and GSH. In addition, the expressions of NF-κB, TNF-α, IL-1ß, caspase-3 and Bax was down-regulated while IL-10 and Bcl-2 expressions were up-regulated with taxifolin treatment. The recovery was confirmed by downregulation of iNOS and 8-OHdG expressions in our immunohistochemical analysis. Taxifolin treatment reduced the disrupting role of thioacetamide as seen by corrected hyperammonemia as well as preservation of astrocyte and hepatocyte structure. Elevated plus maze and locomotor activity tests also proved that taxifolin might repeal the neurobehavioral disabilities. In conclusion, taxifolin has shown hepatoprotective and neuroprotective roles with antioxidant and anti-inflammatory effects, as well as suppressing the excessive release of ammonia, and it eventually reversed neurobehavioral impairments.

Investigation of leptospiral antigen with immunohistochemical and immunofluorescence methods in cattle kidney.

In this study, it was aimed to determine the presence of Leptospira interrogans antigens in the kidney samples of naturally infected cattle by immunohistochemical and immunofluorescence methods. 70 bovine kidney samples showing macroscopic lesions were examined by immunohistochemical and immunofluorescence methods. The positivity of Leptospira interrogans antigens was detected in 5 (7.14%) kidney samples examined by both methods. As a result; The presence of Leptospira interrogans antigens detected by IHC and IF staining methods in bovine kidneys where research samples were provided was found at the same rates (7.14%). Although it has low rates compared to previous studies, it has been determined that it is current and creates problems in terms of animal health.

Genome-wide profiling of the expression of serum derived exosomal circRNAs in patients with hepatic alveolar echinococcosis.

The patients with hepatic alveolar echinococcosis is poorly detected due to invasive and slow growth. Thus, early diagnosis of hepatic alveolar echinococcosis is so important for patients. Circular RNAs are crucial types of the non-coding RNA. Recent studies have provided serum-derived exosomal circRNAs as potential biomarkers for detection of various diseases. The clinical importance of exosomal circRNAs in hepatic alveolar echinococcosis have never been explored before. Here, we investigated the serum-derived exosomal circRNAs in the diagnosis of hepatic alveolar echinococcosis. Firstly, High-throughput Sequencing was performed using 9 hepatic alveolar echinococcosis and 9 control samples to detect hepatic alveolar echinococcosis related circRNAs. Afterwards, bioinformatic analyzes were performed to identify differentially expressed circRNAs and pathway analyzes were performed. Finally, validation of the determined circRNAs was performed using RT-PCR. The sequencing data indicated that 59 differentially expressed circRNAs; 31 up-regulated and 28 down-regulated circRNA in hepatic alveolar echinococcosis patients. The top 5 up-regulated and down-regulated circRNAs were selected for validation by RT-qPCR assay. As a result of the verification, circRNAs that were significantly up- and down-regulated showed an expression profile consistent with the results obtained. Importantly, our findings suggested that identified exosomal circRNAs could be a potential biomarker for the detection of hepatic alveolar echinococcosis serum and may help to understand the pathogenesis of hepatic alveolar echinococcosis.

Amelioration of oxidative damage parameters by carvacrol on methanol-induced liver injury in rats.

The methanol metabolite that causes hepatotoxicity is formic acid, generating reactive oxygen radical formation and cell damage. Carvacrol is an antioxidant monoterpenic phenol produced from Thymus vulgaris. This study aimed to investigate the effects of carvacrol on methanol-induced oxidative liver damage in rats. Eighteen rats were divided into three groups. Methotrexate was administered orally for 7 days to methotrexate+methanol (MTM) and methotrexate+methanol+carvacrol (MMC) groups. Methotrexate was given before methanol to cause methanol poisoning. Distilled water was given to the healthy group (HG) as a solvent. At the end of the 7th day, 20% methanol was administered orally at a dose of 3 g/kg to the MTM and MMC groups. Four hours after methanol administration, 50 mg/kg carvacrol was injected intraperitoneally into the MMC group. Animals were sacrificed 8 h after carvacrol injection. Biochemical markers were studied in the excised liver tissue and blood serum samples, and histopathological evaluations were made. Severe hemorrhage, hydropic degeneration, pycnosis, and mononuclear cell infiltration were observed in the liver of the MTM group. Additionally, the levels of malondialdehyde (MDA), total oxidant status (TOS), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were significantly higher, and total glutathione (tGSH) and total antioxidant status (TAS) were significantly lower in the MTM group compared to HG (P<0.001). Carvacrol prevented the increase in MDA, TOS, ALT and AST levels with methanol and the decrease in tGSH and TAS levels (P<0.001), and alleviated the histopathological damage. Carvacrol may be useful in the treatment of methanol-induced liver damage.

Early administration of milrinone ameliorates lung and kidney injury during sepsis in juvenile rats.

BACKGROUND: A sepsis model was created, induced by cecal ligation and puncture (CLP), in juvenile rat groups. Milrinone (MIL), which is known to have a modulatory effect on pro-inflammatory cytokines, was administered to the designated rat groups in the early period before severe sepsis developed. The study was aimed at investigating the possible protective effects of milrinone on the lung and kidney tissues of rats in the late phase of sepsis. METHODS: The rat pups were divided into seven groups with six animals in each group: (1) healthy rats who received no drug; (2) CLP-S12 (sacrificed at hour 12); (3) CLP-S24 (sacrificed at hour 24); (4) CLP-MIL1-S12 (administered with 0.5 mg/kg milrinone at hour 1 and sacrificed at hour 12); (5) CLP-MIL1-S24 (administered with 0.5 mg/kg milrinone at hour 1 and sacrificed at hour 24): (6) CLP-MIL12-S24 (administered with 0.5 mg/kg milrinone at hour 12 and sacrificed at hour 24), (7) and CLP-MIL1,12-S24 (administered with 0.5 mg/kg milrinone at hours 1 and 12 and sacrificed at hour 24). RESULTS: Significant differences were found between the early and late administration of milrinone in terms of both molecular and histopathological results. The results showed that the tissues were significantly preserved in the groups in which milrinone had been started in the early period compared to the sepsis control groups and the groups in which milrinone had been started in the late period. CONCLUSIONS: In addition to the positive inotropic effects of milrinone, its immunomodulatory properties that result in decreased cytokine storm can be beneficial during early period of sepsis.

Apoptosis is induced by sub-acute exposure to 3-MCPD and glycidol on Wistar Albino rat brain cells.

3-chloropropane-1,2-diol (3-MCPD) and its toxic metabolite glycidol were classified by the International Agency for Research on Cancer (IARC) as belonging to group 2B and 2A for humans. This study aimed to determine the sub-acute toxicity of these agents. Rats were exposed to 3-MCPD at 0.87 and 10 mg/kg/bw and glycidol (2,4 and 37,5 mg/kg/bw) for 90 days. miR-21 gene expression levels significantly decreased in all group's cerebellar tissues compared with control. Exposure to 10 mg/kg/bw 3-MCPD showed significant increases in PTEN in brain as compared to control group. The Akt gen expressions were significantly decreased in 3-MCPD and glycidol groups when compared to control group brains. Additionally, Caspase 3 and AIF immunopositivity significantly increased in 3-MCPD high dose and glycidol high dose groups in cerebellum granular layers compared to control. The results of the present study conclude that 3-MCPD and glycidol can induce apoptosis in rat brain tissue.

Teratogenic and Neurotoxic Effects of n-Butanol on Zebrafish Development.

In recent years, n-butanol, a type of alcohol, has been widely used from the chemical industry to the food industry. In this study, toxic effects of n-butanol's different concentrations (10, 50, 250, 500, 750, 1,000, and 1,250 mg/L) in Zebrafish Danio rerio embryos and larvae were investigated. For this purpose, Zebrafish embryos were exposed to n-butanol in acute semistatic applications. Teratogenic effects such as cardiac edema, scoliosis, lordosis, head development abnormality, yolk sac edema, and tail abnormality were determined at different time intervals (24, 48, 72, 96, and 120 h). Additionally, histopathological abnormalities such as vacuole formation in brain tissue and necrosis in liver tissue were observed at high doses (500, 750, and 1,000 mg/L) in all treatment groups at 96 h. It was determined that heart rate decreased at 48, 72, and 96 h due to an increase in concentration. In addition, alcohol-induced eye size reduction (microphthalmia) and single eye formation (cyclopia) are also among the effects observed in our research findings. In conclusion, n-butanol has been observed to cause intense neurotoxic, teratogenic, and cardiotoxic effects in Zebrafish embryos and larvae.