Assessment of redox homeostasis via genotoxicity, cytotoxicity, apoptosis and NRF-2 in colorectal cancer cell lines after treatment with Ganoderma lucidum extract.

This study aimed to investigate the cytotoxic and apoptotic effects of Ganoderma lucidum, Pleurotus ostreatus, Pleurotus eryngii, and Inonotus hispidus fungal extracts on HT-29 and HCT-116 colorectal cancer cell lines and to search the DNA damage and oxidative stress caused by these extracts. Accordingly, mushroom extracts were applied to colorectal cancer cell lines in vitro, and the IC50 result was obtained with the MTT test. According to the IC50 result, Ganoderma lucidum extract had the most effective cytotoxicity value among all used mushroom extracts. TAS, TOS, and NRF-2 tests were used to investigate the molecular effect of Ganoderma lucidum extract on oxidative stress; the DNA ladder test was performed to assess DNA damage, the Scratch assay method was applied for cell migration analysis, and the colony assay was used to determine the colony formation potential of the cells. The results showed that Ganoderma lucidum mushroom extract reduces cell proliferation, colony formation, and NRF-2, induces DNA damage, slows cell migration, and increases oxidative stress. This study shows that Ganoderma lucidum mushroom extract reduces cell proliferation through damaging cellular DNA and has a cytotoxic effect in colorectal cancer cell lines.

The effect of a bis-structured Schiff base on apoptosis, cytotoxicity, and DNA damage of breast cancer cells.

Developing new anticancer agents are crucial for cancer treatment. Antiproliferative activity of L1H as a bis-structured Schiff base was subjected to preliminary research in eight different kinds of cell lines by the cell viability method using different concentrations to determine their inhibitory concentration. L1H demonstrated the highest cytotoxicity in human breast cancer cell line MCF-7. In this perspective, the MCF-7 cell line was cultured for the examination of different molecular techniques, including MTT, apoptosis analysis by enzyme-linked immunosorbent assay (ELISA), and comet assay. Moreover, the DNA ladder, acridine orange/ethidium bromide as another apoptotic cell analysis, markers of oxidative stress, and total antioxidant status, total thiol, and GSH as nonenzymatic antioxidants assay were conducted. The above techniques have proven that L1H is a growth inhibitor effect when compared to cisplatin as a positive control in human breast cancer cells, especially those affected by L1H. The findings clearly show that L1H evaluated in MCF-7 cell lines causes rising or induced apoptosis, DNA damage, diminished antioxidant status against the increase of oxidized protein, and prevents cell proliferation. Manifold evidence supported our hypothesis that L1H has a potential therapeutically improved effect against the MCF-7 cell line, and then without a doubt is a suitable candidate drug for investigating cancers next.

Evaluation of the relationship of IL-17A and IL-17F gene polymorphisms with the response to treatment in psoriatic patients using biological drugs: a case-control study in patients in Eastern Turkey.

INTRODUCTION: IL-17A and IL-17F cytokines have important roles in the pathogenesis of psoriasis. AIM: To examine the associations of IL-17A rs2275913 and IL-17F rs763780 variants with the development of psoriasis and whether these polymorphisms affect the responsiveness of biological agents. MATERIAL AND METHODS: In our case-controlled study, which included 83 psoriatic patients who were treated with different biological agents and 69 healthy controls, we genotyped IL-17A rs2275913 and IL-17F rs763780 variants using TaqMan probes. RESULTS: We did not observe statistically significant changes in genotype frequencies of IL-17A rs2275913 (p = 0.922) and IL-17F rs763780 (p = 0.621) variants between patient and control groups. Although we did not find any association between these polymorphisms and the development of psoriasis, statistical analyses showed that individuals with the IL-17A AA genotype had shorter disease duration (9.09 ±6.82, p = 0.020) and AA genotype frequency was higher in patients who used single conventional treatment (34.6%; p = 0.025). IL17A/rs2275913 variant in terms of disease duration, it was observed that individuals with AA genotype had a shorter disease duration (less than 10 years) (p = 0.009). For patients with PASI90 and PASI100 response, the IL-17A AA genotype was significantly higher (p = 0.015). On the other hand, we did not detect any statistically significant correlation between variants and response to biological agents. CONCLUSIONS: According to our results, we may suggest that rs2275913 variant seems to be associated with disease duration, use of single conventional treatment and responsiveness of PASI90 and PASI100 however both variants have no effect on the susceptibility to psoriasis in the population of Eastern Turkey.

Evaluation of the anticancer potential of a sulphonamide carbonic anhydrase IX inhibitor on cervical cancer cells.

Cervical cancer is a common type of cancer. Carbonic anhydrase IX (CA IX) is an attractive target for tumour therapy, being overexpressed in many cancers. We investigated the anticancer properties of the aromatic sulphonamide S-1 as a CA IX inhibitor on cervical cancer cells (HeLa) positive for CA IX expression and normal prostate epithelial cell line (PNT1-A) negative for CA IX. We examined the cytotoxic, apoptosis, genotoxic, and oxidative stress activity of S-1 on HeLa and PNT1-A cell lines. S-1 induced significant reduction of cell viability, caused apoptosis, and up-regulated ROS production. This decrease in cell survival rate can be attributed to the high level of ROS and apoptosis, which has also been shown to arrest the cell cycle. Our findings indicated that S-1 is more effective on HeLa than PNT1-A. S-1 was able to induce apoptosis of cervical cancer cells and is a possible candidate for future anticancer studies.

The cytotoxic, apoptotic and oxidative effects of carbonic anhydrase IX inhibitor on colorectal cancer cells.

Colorectal cancer (CRC) is the third most common tumor, malignant and has developed one of the main reasons of cancer mortality. According to studies conducted recently; carbonic anhydrase 9 (CAIX) is an especially attractive target for cancer therapy, in part since it is limited way expressed in normal tissues on the other hand in a wide variety of solid neoplasia are overexpressed. The aim of this study was to appreciate the effects of CAIX inhibitor, namely novel synthesized sulfonamide derivative (H-4i) with high affinity for CAIX, in CAIX-positive human colorectal cancer cell (HT-29) and CAIX-negative human normal embryonic kidney cell line (HEK-293). For this reason, we planned to investigate apoptotic, cytotoxic and oxidative stress activity of H-4i on HT-29 and HEK-293 cell lines. Cell viability determined by WST-1 assay afterwards IC50 values, apoptosis and cell cycle induction measured by flow cytometric analysis, intracellular free radical induction performed by reactive oxygen species (ROS) analyses. The IC50 value of the sulfonamide derivative compound was found to be very low, especially in HT-29 cells, when compared to human normal cells. This research found that H-4i significantly increased cytotoxicity and ROS production, caused significant signs of apoptosis level. High level of ROS and apoptosis lead to arrest the cell cycle and reduce cell survival. The most obvious finding to emerge from the analysis that novel synthesized sulfonamide derivative H-4i is effective on HT-29 more than HEK-293. Therefore, novel derivative H-4i might be used as an anti-cancer potential compound on CRC.

The apoptotic, cytotoxic and genotoxic effect of novel binuclear boron-fluoride complex on endometrial cancer.

Endometrial cancer (EC) is one of the most common types of gynecologic cancer of the female genital tract; it considered being the fourth leading death factor among other types of cancer. Therefore, developing new anti-cancer agents are crucial for cancer treatment. Based on the potential of Schiff based complexes for the induction of apoptosis, Schiff base compounds, and their metal complexes displayed excellent anticancer properties. In this current study, antiproliferative activity of [L(BF2)2] as a novel binuclear boron-fluoride complex was examined to preliminary research in eight different cell lines, HELA, DU-145, PC3, DLD-1, ECC-1, PNT1-A, HT-29, and MCF-7, it was found to have a potent, suppressive effect on human endometrial adenocarcinoma cell line ECC-1. Based on this data, later investigated its apoptotic, cytotoxic, and genotoxic properties on human endometrial adenocarcinoma cell line ECC-1 in different concentrations. Apoptotic and cytotoxic tests such as single cell gel electrophoresis assay (comet assay), DNA fragmentation laddering, acridine orange test for DNA damage, and ELISA for apoptotic measurement was performed. We also gauged the oxidative status by evaluating total antioxidant status (TAS) and total oxidant status (TOS). Oxidative stress index (OSI) was calculated too. As a result [L(BF2)2] has been found to have a marvelous effect on ECC-1 cells, especially in damaging their DNA and cause a series of reactions lead to apoptosis. Taken together, it suggests that the [L(BF2)2] complex can induce the apoptotic pathway of endometrial cancer cells and is a possible candidate for future cancer treatment studies.

Oral isotretinoin therapy of acne patients decreases serum paraoxonase-1 activity through increasing oxidative stress.

OBJECTIVES: There are only a few earlier studies suggesting relationship between isotretinoin treatment and oxidative stress however, their results are conflicting. Therefore we aimed to concretize the influence of isotretinoin treatment on oxidant/antioxidant status together with paraoxonase-1 (PON1) activity for the first time. METHODS: The study was performed on serum samples obtained from 35 acne vulgaris patients before and after three months of isotretinoin treatment. PON1 activity, total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI) and some routine biochemical parameters were monitored. RESULTS: Dramatically decreased PON1 activity (p < 0.001), increased TOS level and OSI value (p < 0.001 and p < 0.001; respectively) as well as slightly diminished TAC level were noted in posttreatment stage. Moreover significant increases were observed in lactate dehydrogenase and gamma glutamyl transpeptidase activities and levels of total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, triglycerides, low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio respectively (p < 0.05, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001 and p < 0.001) while marked decrease was seen in high density lipoprotein cholesterol (p < 0.01). CONCLUSION: This study revealed that decreased PON1 activity and increased oxidative stress may have a crucial role in the pathogenesis of isotretinoin's side effects. Further studies on a large number of patients are needed to verify these results.

Anthocyanin-rich extract from Hibiscus sabdariffa calyx counteracts UVC-caused impairments in rats.

CONTEXT: Ultraviolet radiation (UV) was reported to cause oxidative stress. Hibiscus sabdariffa L. (Malvaceae) calyx is commonly used in traditional Asian and African medicines and possesses strong antioxidant capacity due to its anthocyanin (ANTH) content. OBJECTIVE: This study researched the possible protective role of Hibiscus sabdariffa calyx extract (HSCE) in UVC exposure of rats. MATERIAL AND METHODS: Levels of serum enzymes, renal function tests, and some oxidant/antioxidant biomarkers of skin, lens, and retina tissues were monitored. Rats were exposed to UVC 4 h daily for 40 d and simultaneously received HSCE containing 2.5, 5, and 10 mg doses of ANTH in drinking water. RESULTS: Significant (p < 0.05) increases in the levels of serum aminotransferases, lactate dehydrogenase, urea, creatinine, and uric acid were noted after UVC exposure. In skin, lens, and retina tissues, total oxidant status, oxidative stress index, lipid peroxidation, and protein oxidation escalated markedly (p < 0.05) whereas total antioxidant status, reduced glutathione, and superoxide dismutase decreased dramatically (p < 0.05) related to UVC. Co-administration of HSCE with each ANTH dose significantly (p < 0.05) reversed aforementioned parameters (except total oxidant status) almost in all tissues. The LD50 of HSCE in rats was determined to be above 5000 mg/kg. DISCUSSION AND CONCLUSION: Our data revealed that HSCE has a remarkable potential to counteract UVC-caused impairments, probably through its antioxidant and free radical-defusing effects. Therefore, HSCE could be useful against some cutaneous and ocular diseases in which UV and oxidative stress have a role in the etiopathogenesis.

Protective Action of Curcumin and Alpha-lipoic Acid, Against Experimental Ultraviolet-A/B Induced Dermal-injury in Rats.

The objective of this study was to examine the therapeutic efficacy of curcumin (CUR) and α-lipoic acid (ALA) in mitigating UV-A and UV-B-induced damage (UVAB) in rat dorsal skin. This was achieved through the utilisation of immunohistochemical (TUNEL), biochemical and stereological techniques. The rats in the UVAB, UVAB + CUR, and UVAB + ALA groups were subjected to UVAB irradiation for a period of two hours per day over the course of one month. The UVAB + CUR and UVAB + ALA groups were administered 100 mg/kg/day of curcumin and 100 mg/kg/day of α-lipoic acid via gavage 30 min prior to UVAB irradiation. The CUR group was administered 100 mg/kg/day of curcumin via gavage, while the ALA group received the same dose of α-lipoic acid. A significant change in the volume ratio of the dorsal skin epidermis and dermis was observed in the stereological findings of the rats in the UVAB group. These changes exhibited a favourable progression as a consequence of the CUR and ALA applications. In the UVAB group, TOS and OSI were significantly elevated as a consequence of the rise in oxidative stress. Conversely, the treatment groups demonstrated a notable reduction in TOS and OSI levels. The study also revealed a substantial increase in the number of apoptotic cells within the UVAB group. However, the treatment groups exhibited a significant decline in apoptotic cells. In conclusion, the findings suggest that CUR and ALA possess a protective effect against UVAB-induced skin damage.

Exploring Natural Compounds Targeting PD-L1 and STAT3: Toxicogenomic Analysis, Virtual Screening, Molecular Docking, ADMET Evaluation, and Biological Activity Prediction.

BACKGROUND: One of the most important targets in cancer immunotherapy is programmed cell death ligand 1 (PD-L1). Monoclonal antibodies developed for this target have disadvantages due to their low bioavailability and some immune-related adverse effects. Additionally, small molecules targeting PD-L1 are still in the experimental stage. At this point, discovering non-toxic natural compounds that directly or indirectly target PD-L1 is essential. In this in silico study, a comprehensive literature search was conducted to identify publications reporting the master regulator of PD-L1, which was suggested as a Signal Transducer and Activator of Transcription 3 (STAT3). The relationship between STAT3 and PD-L1 was further investigated through bioinformatic analysis. METHOD: Subsequently, natural compounds targeting PD-L1 and STAT3 were screened, and compounds with suitable toxicity profiles were docked against both PD-L1 and STAT3. Following molecular docking, the selected molecules underwent DNA docking, ADMET profile analysis, and in silico assessment of biological activities. The relationship between PD-L1 and STAT3 was determined in 52 out of the 453 articles, and it was further demonstrated in genegene interactions. Following the virtual screening, 76 natural compounds were identified, and after pre-filtering based on physicochemical properties, drug-likeness, and ADMET profiles, 29 compounds remained. RESULT: Subsequent docking revealed that two compounds, 6-Prenylapigenin, and Gelomulide J, persisted. ADMET and biological activity prediction results suggested that 6-Prenylapigenin is non-toxic and has the potential to inhibit PD-L1 and STAT3 in silico. The present study highlights that STAT3 serves as the master regulator of PD-L1, and it further suggests that 6- Prenylapigenin exhibits the potential to modulate PD-L1 and/or STAT3. CONCLUSION: This finding could pave the way for the development of small molecules designed to block the PD-1/PD-L1 interaction by silencing the PD-L1 and/or STAT3 genes or reducing protein levels.

Therapeutic potential of some plant extracts used in Turkish traditional medicine on streptozocin-induced type 1 diabetes mellitus in rats.

Diabetes mellitus (DM) is known to impair many physiological functions. Some reports claim that medicinal plants can reduce these alterations caused by DM. The aim of this study was to investigate the therapeutic potential of aqueous-methanol extracts of Urtica dioica, Thymus vulgaris (TV), Myrtus communis (MC), Scolymus hispanicus (SH) and Cinnamomun zeylanicum (CZ) on streptozotocin (STZ)-induced type 1 DM in rats. Diabetes was induced via a single i.p. injection of STZ (65 mg/kg body weight). After 1 week to allow for development of diabetes, each plant extract was administered to diabetic rats separately at a dose of 100 mg/kg body weight daily for 28 days. The results showed that only SH extract significantly (P < 0.05) amended fasting blood glucose level. The lipid profile was ameliorated especially by supplementations of TV, MC and CZ extracts. Almost all plant extract treatments markedly (P < 0.05) increased reduced glutathione content and decreased lipid peroxidation levels of erythrocyte, plasma, retina and lens tissues. They also significantly (P < 0.05) amended erythrocyte catalase activity, levels of marker serum enzymes (except amylase), urea and blood urea nitrogen when compared to diabetic rats treated with nothing. Furthermore, none of the plant extracts counteracted body weight loss of diabetic rats. Our data revealed that the aforementioned plant extracts have remarkable potential to counteract DM-caused alterations, probably through their antioxidant and free radical-defusing effects.

ROS-mediated Genotoxicity and Apoptosis Induced by a Novel Salicylaldimine Derivatives in Human Cervical Cancer Cells.

BACKGROUND: Cervical cancer is one of the most common types of cancer among women. Therefore, cancer studies are underway for a new chemo-agent with more effect on cancer cells and fewer side effects on normal human healthy cells. The currently studied novel ligand L2b as a reduced salicylaldimine derivative was examined in seven cell lines, HeLa, DU-145, PC3, DLD-1, ECC, HT-29, and PNT1-A as a control. AIM: Because of the antiproliferative ability of L2b, this study intends to look at the apoptotic, cytotoxic, and genotoxic activity of L2b on HeLa. METHODS: For this purpose, MTT assay is for screening cytotoxic effects, comet assay for looking for DNA damaging or genotoxicity levels, ELISA and DNA fragmentation for apoptotic measuring, AO/EB stain test for checking the rates of live, apoptotic and necrotic cells were performed. To reveal the oxidative state, OSI was assessed by total oxidant and antioxidant status ratios. FRAP assay was calculated for ferric-reducing antioxidant power, using total thiol and GSH assays to measure the antioxidant values of HeLa cells. RESULTS: Of this result, we have found a tremendous effect of L2b on HeLa cells, especially in raising the ROS rate, damaging their DNA, and causing a range of reactions leading to apoptosis. CONCLUSION: In conclusion, the data predict which ligand L2b is capable of rising apoptosis in vitro cervical cancer cell line studied. Further cancer studies are needed to reveal the apoptosis pathways of the ligand L2b in the HeLa cell line and its anticancer drug potency in vivo work.

Investigation of the biochemical and histopathological effects of vitamin C, selenium, and therapeutic ultrasound on muscle damage in rats.

Muscle injury is a common type of soft tissue injury. Increased oxidative damage has been reported after muscle injuries. Therapeutic ultrasound is commonly used for such injuries. This study compared the efficacy of therapeutic ultrasound treatment and various antioxidant agents in experimental muscle injuries. For this purpose, some serum enzymes, oxidative stress, and inflammatory markers were evaluated together with histopathological examinations. Six groups were formed with 6 male Wistar albino rats in each group. These groups were control, only injury (OI), ultrasound (U), vitamin C (Vit C), selenium (S), and mixture (M). Muscle injury was caused by a laceration of the gastrocnemius muscle in all groups except the control group. No treatment was performed in the OI group. At the end of the 6-day application, all rats were sacrificed. As for serum enzymes, CK, ALT, and AST levels returned to control values in almost all treatment groups. Total oxidative status (TOS) and oxidative stress index (OSI) increased in the OI group, while they decreased in the S and M groups. In addition, the decrease in MPO activity in the blood tissue of the Vit C group was statistically significant. There were no significant changes between groups in terms of serum inflammatory markers and histological findings. This study has shown that the ingestion of vitamin C and selenium may contribute to the treatment of muscle injury in addition to therapeutic ultrasound treatment. However, further studies are needed to support these results.

Comparison of superoxide dismutase, glutathione peroxidase and adenosine deaminase activities between respiratory and nocturnal subtypes of patients with panic disorder.

OBJECTIVE: There is mounting evidence indicating that oxidative and inflammatory processes may have an important role in the pathogenesis of panic disorder (PD). PD is a heterogeneous disease, and panic attacks are divided according to the different symptom clusters as respiratory, nocturnal, non-fearful, cognitive, or vestibular subtypes. The aim of this study was to compare whole-blood and serum superoxide dismutase (SOD), glutathione peroxidase and adenosine deaminase activities in PD patients with/without nocturnal, respiratory subtypes and healthy subjects. METHODS: The study was conducted including 60 patients with PD and 30 healthy control subjects. The Panic Attack Symptom Checklist, Panic and Agoraphobia Scale, Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale were administered to the patients. Biochemical analyses were performed after all the blood samples were collected. RESULTS: We found that whole-blood SOD and glutathione peroxidase activities of patients were significantly lower and adenosine deaminase activities of patients were higher than those of healthy controls. There were no statistically significant differences between respiratory and nocturnal subtypes. In addition, there were no marked relationships between the duration of illness and panic-agoraphobia scores of patients with nocturnal subtypes. Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores of patients with the nocturnal subtype were markedly higher than those of patients without the nocturnal subtype. CONCLUSION: The results suggest that oxidative and inflammatory processes may play a role in the pathophysiology of PD. These findings may support the idea that both nocturnal and respiratory subtypes of PD have different symptom clusters of the same disease.

Ameliorative influence of Urtica dioica L against cisplatin-induced toxicity in mice bearing Ehrlich ascites carcinoma.

Cisplatin (CP) is a widely used cytotoxic agent against cancer, and high doses of CP have been known to cause nephrotoxicity and hepatotoxicity. Some reports claim that antioxidants can reduce CP-induced toxicity. This study investigated the hepatoprotective, nephroprotective, and antioxidant activity of Urtica dioica L methanolic extract (UDME) against CP toxicity in Erhlich ascites tumor (EAT)-bearing mice. Levels of serum hepatic enzymes, renal function markers, and oxidant/antioxidant parameters of liver tissue were measured. Mice were inoculated with EAT on day 0 and treated with nothing else for 24 hours. After a single dose of CP administration on day 1, the extract was given at the doses of 50, 100, 200, and 400 mg/kg body weight daily during 6 days. Almost all doses of UDME performed a significant (P < 0.05) preventive role against CP toxicity by decreasing aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, blood urea nitrogen, creatinine, lipid peroxidation, protein oxidation levels, and myeloperoxidase activity, as well as increasing reduced glutathione content, superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase activities. This suggests that UDME has a protective capacity and antioxidant activity against CP toxicity in EAT-bearing mice, probably by promoting antioxidative defense systems.

Photoprotective effect of flax seed oil (Linum usitatissimum L.) against ultraviolet C-induced apoptosis and oxidative stress in rats.

The aim of this study is to determine antioxidant and antiapoptotic effects of flax seed oil (FSO) on rats exposed to ultraviolet C (UVC). Malondialdehyde (MDA), protein carbonyl (PC) and reduced glutathione (GSH) levels as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured in lens, skin and serum. In addition, ß-carotene, vitamin A, C and E contents were measured in serum, while apoptosis was determined in retina. Rats were divided into three groups as control, UVC and UVC + FSO. UVC and UVC + FSO groups were exposed to UVC light for 1 h twice a day for 4 weeks. FSO (4 ml/kg bw) was given by gavage before each irradiation period to the UV + FSO group. While MDA and PC levels of the UVC group increased compared to the control group, their levels decreased in the UVC + FSO group compared with the UVC group in skin, lens and serum. Skin GSH level decreased significantly in the UVC and UVC + FSO groups. As GPx and SOD activities of the UVC group were lower, their activities were higher in the UVC + FSO group in skin, lens and serum. There was only marked elevation of vitamin A level in the UVC group compared to the control group. Apoptosis increased in the UVC group and the UVC + FSO groups in retina. However, retinal apoptosis were lower in the UVC + FSO group compared with the UVC group. This investigation demonstrated that UVC exposure led to oxidative stress and apoptosis in rats as reflected by increased MDA, PC contents and decreased enzymatic and nonenzymatic antioxidant levels, FSO may be useful for preventing photoreactive damage.

Subacute effect of cigarette smoke exposure in rats: protection by pot marigold (Calendula officinalis L.) extract.

This study was carried out to determine the preventive effect of Calendula officinalis L. (pot marigold) on rats exposed to cigarette smoke (CS). Rats were divided into three groups as control, CS and CS + pot marigold (PM). The rats in the CS and CS + PM groups were subjected to CS for 1 h twice a day for 23 days. PM (100 mg/kg body weight) was given to rats in the CS + PM group by gavage, 1 h before each administration period. While malondialdehyde, protein carbonyl contents and reduced glutathione level of the CS group increased, their levels diminished by PM administration. In addition, glutathione peroxidase (GPx), superoxide dismutase activities and ß-carotene, vitamins A and C levels decreased in the CS group compared to control, however activities of these enzymes and concentration of vitamins were elevated by PM supplementation. This investigation showed that administration of PM supplied relative protection against subacute CS-induced cell injury.

Omethoate modulates some oxidant/antioxidant parameters in frogs (Rana ridibunda Pallas).

The aim of this study was to investigate the effect of an organophosphorus insecticide omethoate (OM), on certain oxidative stress biomarkers (malondialdehyde (MDA), reduced glutathione (GSH), glutathione-S-transferase (GST), glutathione reductase (GR), catalase (CAT)) in tongue, lung, stomach and muscle tissues of adult frogs (Rana ridibunda Pallas). Animals were exposed to 10 and 20 parts per million dosages of OM for 24, 48, 72 or 96 h. According to the results, MDA level increased significantly in lung and stomach tissues. GSH content fluctuated in lung and muscle while it elevated in tongue and stomach tissues. With regard to antioxidant enzymes (GST, GR and CAT), their activities reduced in tongue, while they increased in lung and fluctuated in stomach and muscle tissues. It can be concluded that exposure of frogs to OM are characterized by increased MDA levels and fluctuated enzyme activities and GSH contents. This may reflect the potential role of these parameters as useful biomarkers for assessment of OM toxicity.

Valproic Acid Attenuated PTZ-induced Oxidative Stress, Inflammation, and Apoptosis in the SH-SY5Y Cells via Modulating the TRPM2 Channel.

Valproic acid (VPA) is one of the most widely used antiepileptic drugs. The protective role of VPA and the role of the TRPM2 channel in this mechanism in developing neuronal damage due to increased pentylenetetrazol (PTZ)-induced neurotoxicity in SH-SY5Y cells were not clarified. Here, we investigated the role of VPA via modulation of TRPM2 channel on cell death and oxidative neurotoxicity in SH-SY5Y cells. The SH-SY5Y cell toxicity model was constructed by treating SH-SY5Y cells with PTZ. The VPA and TRPM2 channel antagonist N-(p-amylcinnamoyl) anthranilic acid (ACA) were added to prevent neurotoxicity in PTZ-induced SH-SY5Y cells. The role of the VPA and TRPM2 channel was evaluated using an ELISA kit and patch-clamp. Primarily, antioxidant (GSH and GSH-Px) and oxidative stress (MDA and ROS) levels and inflammatory factors (IL-1ß, IL-6, and TNF-α) in cells were determined by ELISA kits. Then, TRPM2 channel activation in cells was detected using both the ELISA kit and patch-clamp methods. In addition, apoptosis and cell viability levels in cells were determined by performing PARP1, caspase-3, caspase-9, and CCK-8 assays by ELISA kits. Our results showed that the TRPM2 channel is vital in damage formation in PTZ-induced cells. Furthermore, we observed that VPA attenuated PTZ-induced neurotoxicity by suppressing cells' oxidative stress and inflammation, and reducing TRPM2 channel activation. In our study, in which the protective effect of VPA and the role of the TRPM2 channel in PTZ-induced SH-SY5Y cells were investigated for the first time, we can conclude that VPA treatment and TRPM2 channel blockade can suppress PTZ-induced neurotoxicity.

Increased occupational coal dust toxicity in blood of central heating system workers.

Coal dust causes lung diseases in occupational exposure. Reactive oxygen species have been implicated in the pathogenesis of its toxicity. In this study, serum enzymes, lipid profile and other biochemical values with oxidant/antioxidant status in whole blood and serum of central heating system workers (CHSW; the persons responsible for heating the apartment with coal) were determined to reflect the cell injury. Blood samples were obtained from CHSW (n = 25) and healthy individuals (n = 25). All values were measured in whole blood and serum. ANOVA was used for the estimation of statistical data. In the group of CHSW, creatinine, ferritin, alanin aminotransferase, aspartate aminotransferase, creatine phosphokinase, gamma glutamyl transferase, lactate dehydrogenase and glutathione reductase activities as well as triglyceride, very low density lipoprotein, protein carbonyl and malondialdehide were significantly higher, while transferrin, high density lipoprotein and catalase (CAT) activities were lower than the group of healthy individuals. This result is consistent with hypothesis that respirable coal dust generates lipid and protein oxidation and induces leakage of serum enzymes by cell damage. It also leads to imbalance in antioxidant defense system, lipid profile and other biochemical parameters.