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Lung ischemia-reperfusion injury (LIRI) causes oxidative stress, inflammation, and immune system activation. The Nrf2/Keap1/HO-1 pathway is important in cellular defense against these effects. Quercetin, a flavonoid with antioxidant, anti-inflammatory, and anti-cancer properties, has been investigated. Our aim in this study was to investigate the effect of quercetin on preventing lung ischemia-reperfusion injury and the role of the Nrf2/Keap1/HO-1 pathway. Sixty-four male Wistar rats were divided into four distinct groups(n = 16). Sham, lung ischemia-reperfusion (LIR), Saline + LIR, Quercetin + LIR (30 mg/kg i.p for a week before LIR). LIR groups were subjected to 60 min of ischemia (left pulmonary artery, vein, and bronchus) and 120 min of reperfusion. Our assessment encompassed a comprehensive analysis of various factors, including the evaluation of expression Nrf2, Keap1, and Heme Oxygenase-1 (HO-1) levels and NF-κB protein. Furthermore, we examined markers related to inflammation (interleukin-1β and tumor necrosis factor alpha), oxidative stress (malondialdehyde, total oxidant status, superoxide dismutase, glutathione peroxidase, total antioxidant capacity), lung edema (Wet/dry lung weight ratio and total protein concentration), apoptosis (Bax and Bcl2 protein), and histopathological alterations (intra-alveolar edema, alveolar hemorrhage, and neutrophil infiltration). Our results show that ischemia-reperfusion results in heightened inflammation, oxidative stress, apoptosis, lung edema, and histopathological damage. Quercetin showed preventive effects by reducing these markers, acting through modulation of the Nrf2/Keap1 pathway and inhibiting the NF-κB pathway. This anti-inflammatory effect, complementary to the antioxidant effects of quercetin, provides a multifaceted approach to cell protection that is important for developing therapeutic strategies against ischemia-reperfusion injury and could be helpful in preventive strategies against ischemia-reperfusion., (© 2024. The Author(s).)

Chlorpyrifos (CPF) is a widely used pesticide that can impair body organs. Nonetheless, metformin is known for its protective role against dysfunction at cellular and molecular levels led by inflammatory and oxidative stress. This study aimed to investigate the modulatory impacts of metformin on CPF-induced heart and lung damage. Following the treatment of Wistar rats with different combinations of metformin and CPF, plasma, as well as heart and lung tissues, were isolated to examine the level of oxidative stress biomarkers like reactive oxygen species (ROS) and malondialdehyde (MDA), inflammatory cytokines such as tumor necrosis alpha (TNF-α), high mobility group box 1 (HMGB1) gene, deoxyribonucleic acid (DNA) damage, lactate, ADP/ATP ratio, expression of relevant genes ( TRADD, TERT, KL ), and along with histological analysis. Based on the findings, metformin significantly modulates the impairments in heart and lung tissues induced by CPF.

Oxidative stress has an important role in brain aging and its consequences include cognitive decline and physiological disorders. Peroxisome proliferator-activated receptor-γ (PPARγ) activation has been suggested to decrease oxidative stress. In the current research, the effect of PPARγ activation by pioglitazone(Pio) on learning, memory and oxidative stress was evaluated in aged rats. The rats were divided into five groups. In the Control group, vehicle (saline-diluted dimethyl sulfoxide (DMSO)) and saline were injected instead of Pio and scopolamine (Sco), respectively. In the Sco group, the vehicle was injected instead of Pio and the rats were injected by Sco 30 min before the behavioral tests. In the Sco-Pio 10, Sco-Pio 20, and Sco-Pio 30 groups, 10, 20, and 30 mg/kg Pio was injected and finally, the rats were injected with Sco 30 min before the behavioral tests. Morris water mater maze(MWM) and passive avoidance(PA) tests were carried out, and finally, the hippocampus and cortex were removed for biochemical assessments. The results showed that the highest dose of Pio decreased the traveling time and distance during 5 days of learning and increased the time and distance in the target area on the probe day of MWM. The highest dose of Pio also prolonged the delay time for entering the dark and total time spent in the light while decreasing the total time spent in and the number of entries into the dark in PA test. Pio especially, in the medium and highest doses, decreased MDA while increasing thiol, superoxide dismutase, and catalase in the hippocampus and cortex. It is concluded that PPARγ activation by Pio as an agonist improved learning and memory in aged rats probably by attenuating oxidative stress in the hippocampus and cortex., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Varicocele is one of the major causes of infertility in men in which testicular function is progressively damaged., Objectives: This study aimed to determine the effect of ghrelin on antioxidant enzymes activity (catalase, SOD, GPx), malondialdehyde (MDA) level and spermatogenesis cycle after induction of varicocele in rat., Materials and Methods: Twenty-one male Wistar rats were randomly divided into three groups: I-control group, II-rats with induced varicocele and injection of physiological saline and III-rats with induced varicocele and injection of ghrelin. At the end of the experiment, animals were sacrificed and their testes were removed. Antioxidant enzymes activity and MDA level were measured. Histopathological tests, Johnsen's score and sperm parameters were also evaluated., Results: In varicocele group with ghrelin administration (group III), the levels of SOD (0.183 ± 0.024), GPX (9.4250 ± 0.103) and TAC (2.79 ± 0.464) increased significantly (p < 0.05), while MDA (0.304 ± 0.004) level decreased significantly (p < 0.05) compared with varicocele and normal saline group (II). There was no significant difference in the activity of catalase between group III (0.122 ± 0.018) and group II (0.108 ± 0.018), although ghrelin improved catalase activity in group III compared to group II. Also, in group III, there were significant increases in the Johnsen's score (7.920), sperm count (70.29 ± 5.82) and sperm viability (87.14 ± 5.21) compared with group II (p < 0.05)., Conclusion: Ghrelin can improve the capacity of antioxidant enzymes to reduce the oxidative stress caused by varicocele and reduce spermatogenesis cycle. Therefore, special attention should be paid to ghrelin in studies evaluating antioxidant compounds in varicocele., (© 2018 Blackwell Verlag GmbH.)

Diabetic neuropathy (DN) is the most common diabetic complication. It is estimated diabetic population will increase to 592 million by the year 2035. This is while at least 50-60% of all diabetic patients will suffer from neuropathy in their lifetime. Oxidative stress, mitochondrial dysfunction, apoptosis, and inflammation are crucial pathways in development and progression of DN. Since there is also no selective and effective therapeutic agent to prevent or treat high glucose (HG)-induced neuronal cell injury, it is crucial to explore tools by which one can reduce factors related to these pathways. Phosphodiesterase 4 and 7 (PDE 4 and 7) regulate oxidative damage, neurodegenaration, and inflammatory responses through modulation of cyclic adenosine monophosphate (cAMP) level, and thus can be as important drug targets for regulating DN. The aim of this study was to evaluate the protective effects of inhibitors of PDE 4 and 7, named rolipram and BRL5048, on HG-induced neurotoxicity in PC12 cells as an in vitro cellular model for DN and determine the possible mechanisms for theirs effects. We report that the PC12 cells pre-treatment with rolipram (2 μM) and/or BRL5048 (0.2 μM) for 60 min and then exposing the cells to HG (4.5 g/L for 72 h) or normal glucose (NG) (1 g/L for 72 h) condition show: (1) significant attenuation in ROS, MDA and TNF-a levels, Bax/Bcl-2 ratio, expression of caspase 3 and UCP2 proteins; (2) significant increase in viability, GSH/GSSG ratio, MMP and ATP levels. All these data together led us to propose PDE 4 and 7 inhibitors, and specifically, rolipram and BRL5048, as potential drugs candidate to be further studied for the prevention and treatment of DN.

Aim: To investigate the side effects of phosalone on intestinal cells and to evaluate benefits of ellagic acid (EA) as a remedy., Methods: In order to conduct an in vivo study, a rat model was used. The rats were divided into ten groups based on the materials used in the experiment and their dosage. The first group was fed normally. The second group was administered EA through gavage. Next Four groups were given (1/3, 1/5, 1/10, 1/20) LD50 phosalone; an organophosphorus compound. The last four groups received (1/3, 1/5, 1/10, 1/20) LD50 phosalone and of EA. After one month, the rats were sacrificed and their colon cells were examined to evaluate the level of inflammation, proteins and oxidative stress markers., Results: The results of this research show that phosalone elevates oxidative stress and changes the level of tumor necrosis factor-a (TNF-α), interlukin-6β (IL-6β) and nuclear factor (NF)-κB proteins. EA administration reduced phosalone toxicity and changed oxidative stress and inflammatory markers for all phosalone doses. Overall changes in reduction of TNF-α (230.47 ± 16.55 pg/mg protein vs 546.43 ± 45.24 pg/mg protein, P < 0.001), IL-6β (15.85 ± 1.03 pg/mg protein vs 21.55 ± 1.3 pg/mg protein, P < 0.05), and NF-κB (32.47 ± 4.85 pg/mg protein vs 51.41 ± 0.71 pg/mg protein, P < 0.05) manifest that the efficacy of EA is more viable for 1/3 LD50 dose of phosalone. Furthermore, EA is effective to counteract the negative outcomes of oxidative stress. When EA was used to treat 1/3 LD50 of phosalone's side effects, it improved the level of AChE activity (48.5% ± 6% vs 25% ± 7%, P < 0.05), TTM (0.391 ± 0.008 mmol/L vs 0.249 ± 0.032 mmol/L, P < 0.05), FRAP (46.04 ± 5.005 μmol/L vs 18.22 ± 1.9 μmol/L, P < 0.01) and MPO (0.222 ± 0.019 U/mg protein vs 0.387 ± 0.04 U/mg protein, P < 0.05)., Conclusion: This research highlights that EA is effective to alleviate the side effects of phosalone by reducing the level of oxidative stress and inflammatory proteins.

Benzene (C6H6) is one of the most commonly used industrial chemicals causing environmental pollution. This study aimed to examine the effect of benzene and its metabolite hydroquinone on glucose regulating organs, liver and pancreas, and to reveal the involved toxic mechanisms, in rats. In the in vivo part, benzene was dissolved in corn oil and administered through intragastric route at doses of 200, 400 and 800 mg/kg/day, for 4 weeks. And, in the in vitro part, toxic mechanisms responsible for weakening the antioxidant system in islets of Langerhans by hydroquinone at different concentrations (0.25, 0.5 and 1 mM), were revealed. Benzene exposure raised the activity of phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase) enzymes and increased fasting blood sugar (FBS) in comparison to control animals. Also, the activity of hepatic glucokinase (GK) was decreased significantly. Along with, a significant increase was observed in hepatic tumor necrosis factor (TNF-α) and plasma insulin in benzene treated rats. Moreover, benzene caused a significant rise in hepatic lipid peroxidation, DNA damage and oxidation of proteins. In islets of Langerhans, hydroquinone was found to decrease the capability of antioxidant system to fight free radicals. Also, the level of death proteases (caspase 3 and caspase 9) was found higher in hydroquinone exposed islets. The current study demonstrated that benzene and hydroquinone causes toxic effects on liver and pancreatic islets by causing oxidative impairment.

Although toxic effects of zinc oxide nanoparticles (ZnO NPs) have been previously studied, there are still controversies in terms of dose, size, shape, and affecting cells. By such a perspective, in this study, small size of ZnO NPs with a diameter of 10 nm at low concentrations was studied for any effect on the viability and function of isolated rat pancreatic islets. Islets of Langerhans were isolated and assessed for viability, functionality (insulin secretion), cytosolic reactive oxygen species (ROS), and apoptosis by flow cytometry. The LC50 of ZnO NPs was found at 1,400 ng/mL at the first phase of the study. A meaningful increase in viability of islets and insulin secretion in basal and even stimulated concentrations of glucose was found by ZnO NPs (70 ng/mL) with p < 0.001 and p < 0.05, respectively. Likewise, ZnO NPs in 70 ng/mL concentration decreased cytosolic ROS generation (p < 0.05). In the meantime, the percentage of early stage of apoptotic cells dropped down to 17 % (from 29 % of control). These results for the first time confirm that ZnO NPs are not only safe when used at dose of 70 ng/mL but also improve viability and function of pancreatic islets and meanwhile reduce oxidative stress and prevent cells from entering the apoptotic phase.