The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin.

Alpha cypermethrin (α-CYP) is an insecticide, a member of the group of synthetic pyrethroid pesticides. This study aims to assess the histopathological and biochemical subacute effects of α-CYP on the renal tissues of 48 male Spraque-Dawley adult rats. In this study, the rats were divided into six groups: control, α-CYP (10 mg kg-1), α-CYP (20 mg kg-1), caffeic acid phenethyl ester (CAPE) (10 µmol kg-1), α-CYP + CAPE (10 mg kg-1), and α-CYP + CAPE (20 mg kg-1) groups. The percentage of weight gain was found to be dose-dependent on α-CYP in all groups. As a result of exposure, the normal histological structure of renal tissue was also observed in the control and CAPE groups, while glomerular atrophy and haemorrhage, enlargement of Bowman capsule, glomerular lobulation, and degeneration in distal and proximal tubules were noted in the α-CYP-treated groups with an increased frequency and severity in parallel with the dose increase. Although the severity and intensity of lesions decreased in the α-CYP + CAPE groups, they were statistically insignificant (p > 0.05). A decrease in the antioxidant parameter levels and an increase in oxidant parameters were observed in parallel with the negative effects of the antioxidant system in the α-CYP-treated groups. The groups exposed to CAPE in combination with α-CYP exhibited a therapeutic trend towards normalization in biochemical parameters due to the antioxidant character of CAPE. However, considering the statistical difference between the groups treated with α-CYP alone and CAPE alone, it was observed that the therapeutic features of those chemicals were not robust.

Oxidative Stress and Biochemical Alterations in Patients with Head and Multiple Organ Traumas.

AIM: To evaluate paraoxonase (PON), total antioxidant status (TAS), total oxidant status (TOS), high-density lipoproteins (HDL), CRP, AST, ALT, GGT, ALP levels in patients with head and multiple organ traumas. MATERIAL AND METHODS: The study included 29 male patients undergoing treatment for head and multiple organ traumas. Blood sample analysis was performed on the first, third, and seventh days after trauma. RESULTS: The mean age, duration of hospitalization in the intensive care unit, and intubation period of the study sample was 45 years (range: 9 to 81 years), 4.29 days, and 2.94 days, respectively. One patient died, and 13 underwent surgical intervention. Comparison of PON, TAS, TOS, and CRP levels showed statistically significant differences between the first day and the third and seventh days, although no such differences were seen in HDL levels. A moderately positive correlation was observed between CRP/ AST, CRP/ALT and CRP/GGT, while a moderately negative correlation was seen between CRP/ALP. CONCLUSION: The findings of this study suggest that some oxidative parameters may play a significant role in the prognosis and follow-up of intensive care patients. Moreover, biochemical markers can provide important information about patient response to trauma.

Immunohistochemical distribution of Bcl-2 and p53 apoptotic markers in acetamiprid-induced nephrotoxicity.

Pesticides, which adversely affect the critical metabolic processes of organisms, disrupt the physiological balance by specifically targeting enzymes and may lead to such consequences that may lead to death. It provides benefits in agricultural activities. The p53 protein antagonizes bcl-2, an anti-apoptotic protein character, and induces apoptosis by causing mitochondrial membrane permeability. This study aims to show the effect of acetamiprid, which is an insecticide from the neonicotinoid class, on bcl-2 and p53 immunoreactivity, which has an important place in the apoptotic mechanism in kidney tissue. A total of four groups including control and three experimental groups (the acetamiprid was administered 5, 10, and 15 mg kg-1) were formed in the study. After acetamiprid was administered via gavage for 14 days, the kidney tissues taken from the mice, which were sacrificed by cervical dislocation, were fixed in 10% formaldehyde solution for histological and immunohistochemical analyses, and as a result of routine tissue follow-up, the sections were blocked in paraffin and stained with haematoxylin-eosin and immunostaining. The histopathological examinations revealed that while the kidney tissue had a normal structure in the control group, degeneration in the distal and proximal tubules, glomerular degeneration, increase in the capsular area, glomerular atrophy, and haemorrhage were determined in the acetamiprid groups at increasing severity and frequency depending on the dose of the applied substance. In the kidney tissue, Bcl-2 and p53 immunoreactivity was observed in glomerular cells, sinusoidal epithelium, and proximal and distal tubule cells. The acetamiprid caused pathological changes in the kidneys in the dose range used. This effect also affects the expression of bcl-2 and p53 genes, which are biomarkers in the apoptotic mechanism. As acetamiprid accumulates in tissues, it increases the expression of p53 from cell death receptors, while suppressing the anti-apoptotic bcl-2 expression.

Tissue-specific toxicity of clothianidin on rainbow trout (Oncorhynchus mykiss).

This study was performed to investigate the tissue-specific effects of clothianidin on Oncorhynchus mykiss by evaluating the biochemical and histological alterations following 21 days of treatment to environmentally relevant concentrations of 3, 15, and 30 µg/L. The emerged behavioral changes in feeding and swimming performance were considered as adaptive responses to avoid the chemical. The toxic effect of pesticide on nervous system and osmoregulation was evidenced with the inhibition of AChE and Na+K+-ATPase. The sustained lipid peroxidation, ranging from muscle (196%) > brain (154%) > gill (140%) > kidney (129%), might be suggested as a mechanism mediating the inhibition of membrane-bound enzymes. Histological evaluation showed clothianidin-induced lesions appearing as necrosis, atrophy, and edema in muscle, hyperplasia, and hypertrophy causing shortening and fusion of the secondary lamellae in gill, vacuolization, and hydropic degeneration in brain, degeneration of tubular epithelium, and existence of melanomacrophage centers in kidney. The pronounced degenerative changes observed in gill indicate the vulnerability of tissue possibly due to its role as first contact and entry point for the pesticide. Consequently, clothianidin exerted its toxic effects by altering normal behavior, causing neurotoxicity and disturbing osmoregulation. Moreover, the imposed stress was responded in a tissue-specific manner and histological lesions become more severe with increasing concentration. The findings clearly reveal the potential threat caused by environmentally relevant concentrations of clothianidin to early life stages of fish.

Manifestations of oxidative stress and liver injury in clothianidin exposed Oncorhynchus mykiss.

This investigation was conducted to evaluate the effects of clothianidin, a neonicotinoid insecticide, on hepatic oxidative stress biomarkers, biochemical indices of blood serum and liver integrity in juvenile Oncorhynchus mykiss following 7, 14 and 21 days of application to environmentally relevant concentrations of 3, 15 and 30 µg/l. The observed hypertrophy caused elevation in hepatosomatic index, a significant increase in serum glucose and a decrease in tissue protein level with extended period of exposure were determined. The treatment resulted in a marked induction in the activities of antioxidant enzymes which were accompanied with simultaneous elevation in MDA and protein carbonyl level reflecting loss of membrane integrity and protein function. Histopathological examination showed liver injury manifested as hepatocellular degeneration, fibrosis, vacuolation, congestion, necrosis, steatosis and pyknosis proceding with the concentration. The stressful condition triggered hyperglycemic and hypoproteinemic conditions which might be proposed as general adaptive response. Moreover, altered liver histology reveals the hepatotoxic potential of clothianidin via oxidative stress as a common pathological mechanism leading to liver injury.

Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line.

Apoptosis, overload Ca2+ entry and oxidative stress are induced in neurons by hypoxia. Drug-resistant cancer cells are killed by hypoxic conditions. α-Lipoic acid (ALA) has antioxidant and pro-oxidant functions. The TRPA1 channel is activated by oxidative stress and pro-oxidant ALA may have a regulator role in the TRPA1 activity in the human glioblastoma (DBTRG) cells. The aim of this study was to evaluate if a combination therapy of ALA with a hypoxia can alter the effect of this hypoxia through TRPA1 activation in the DBTRG cells. The DBTRG cells were divided into four treatment groups as control, ALA (50 µM), and hypoxia and hypoxia + ALA. Hypoxia in the cells was induced by CoCl2 (200 µM). Apoptosis, Annexin V, mitochondrial membrane depolarization (JC-1), reactive oxygen species (ROS) production, IL-1ß, IL-18, caspase 3 and 9 values were increased through activation of TRPA1 (cinnamaldehyde) in the cells by the hypoxia induction, although cell viability, reduced glutathione and glutathione peroxidase values were decreased by the treatments. The values were modulated in the cells by TRPA1 blocker (AP18) and ALA treatments. Involvements of TRPA1 activity on values in the cells were also confirmed by patch-clamp and laser confocal microscopy analyses. In conclusion, apoptotic, inflammatory and oxidant effects of hypoxia were increased by activation of TRPA1, but its action on the values was decreased by the ALA treatment. ALA treatment could be used as an effective strategy in the treatment of hypoxia-induced oxidative stress, apoptosis and inflammation in the neurons.

5-Fluorouracil-induced mitochondrial oxidative cytotoxicity and apoptosis are increased in MCF-7 human breast cancer cells by TRPV1 channel activation but not Hypericum perforatum treatment.

5-Fluorouracil (5-FU) is a widely used chemotherapy agent for breast cancer, although drug resistance is a critical issue regarding the use of this agent in the disease. Calcium signaling is a well-known main cause of proliferation and apoptosis in breast cancer cells. Although previous studies have implicated TRPV1 inhibitor, anticancer, and apoptotic roles of Hypericum perforatum (HPer) in several cells, the synergistic inhibition effects of HPer and 5-FU in cancer and the stimulation of ongoing apoptosis have not yet been clarified in MCF-7 cells. Therefore, we investigated the apoptotic and antioxidant properties of 5-FU with/without HPer through activation of TRPV1 in MCF-7 cells. The MCF-7 cells were divided into four groups: the control group, the HPer-treated group (0.3 mM), the 5-FU-treated group (25 µM), and the 5-FU+HPer-treated group. The intracellular free calcium ion concentration ([Ca2+]i) increased with 5-FU treatments, but they decreased with the HPer and HPer+5-FU treatments. The [Ca2+]i is further decreased in the four groups by TRPV1 channel antagonist (capsazepine and 0.01 mM) treatments. However, mitochondrial membrane depolarization and apoptosis levels, and the PARP1, caspase 3, and caspase 9 expression levels were increased by 5-FU treatment, although the values were decreased by the HPer and 5-FU+HPer treatments. Cell viability level was also decreased by 5-FU treatment. In conclusion, antitumor and apoptosis effects of 5-FU are up-regulated by activation of TRPV1 channels, but its action was down-regulated by HPer treatment. It seems that HPer cannot be used for increasing the antitumor effect of 5-FU through modulation of the TRPV1.

Synergic prooxidant, apoptotic and TRPV1 channel activator effects of alpha-lipoic acid and cisplatin in MCF-7 breast cancer cells.

BACKGROUND: Resistance to cisplatin (Cisp) in the treatment of breast cancer is a major obstacle. Alpha-lipoic acid (ALA) has both antioxidant and oxidant properties. ALA has been used on stimulation mechanisms of apoptosis and oxidative stress in the treatment of cancer with a combination of chemotherapeutic agents, although its role on molecular mechanisms in the cancer cells has not been clarified yet. The aim of this study was to evaluate if a combination therapy of ALA with Cisp can alter the effect of this chemotherapy drug in the MCF-7 breast cancer cells. MATERIALS: The MCF-7 cells were divided into four treatment groups as control, Cisp (0.025 mM), ALA (0.05 mM), and Cisp + ALA. RESULTS: Apoptosis, mitochondrial membrane depolarization, reactive oxygen species (ROS) production, lipid peroxidation, PARP1, caspase 3 and 9 expression levels are increased through activating TRPV1 in the cells by the Cisp and ALA treatments, although cell viability, reduced glutathione and glutathione peroxidase (GPx) values were decreased by the treatments. The Cisp and ALA-induced increase of intracellular free Ca2+ concentration was decreased with the TRPV1 blocker, capsazepine. CONCLUSIONS: Apoptosis and oxidant effects of Cisp were increased by activation of TRPV1 channels, but its action on the values was further increased by the ALA treatment. Combination therapy of ALA and Cisp could be used as an effective strategy in the treatment of breast cancer.

Genotoxic effects and LC50 value of NaOCl on Orthrias angorae (Steindachner 1897).

Studies show that different organisms used as bio-indicators have indicated several genotoxic and mutagenic effects of disinfected waters. In this study, the 96 h LC(50 )mean value of NaOCl for Orthrias angorae was calculated to be 0.5509 mg/L. The results showed that NaOCl is highly toxic to O. angorae specimens. Statistical analysis demonstrated a significant increase in micronuclei after the induction of 0.5 mg/L NaOCl concentration after 36 h. The same increase has been reported for 0.37 and 0.5 mg/L NaOCl concentrations after 72 h. Even though the MN frequency of 0.37 mg/L was similar after 36 and 72 h, only 72 h micronuclei frequency was statistically significant. The 72 h MN frequency of the negative control group was smaller than 36 h MN frequency of the negative control group. This discrepancy has led to 72 h MN frequency being statistically significant. MN frequency of 0.25 mg/L NaOCl concentration was insignificant when compared to negative test groups. The benzene treatment also caused a significant increase (p < 0.01) in the frequency of micronucleated erythrocytes.