Tissue Malondialdehyde Levels Research Articles

Sodium Selenite Modulates IDO1/Kynurenine, TLR4, NF-κB and Bcl2/Bax Pathway and Mitigates Acetic Acid-Induced Colitis in Rat.

Colitis is a main presentation of inflammatory bowel disease (IBD) and yet, has no definitive cure. Currently, corticosteroids, anti-tumor necrosis factor (anti-TNF) agents and 5-aminosalicylic acid derivatives are prescribed for management of colitis. Except their failure rate, they are not always tolerated because of their severe adverse effects. Additive formulas with fewer adverse effects may improve the treatment of colitis. In this study, colitis was induced with intra-rectal injection of three concentrations of acetic acid (4, 6 and 8 v/v). Each group received sodium selenite (0.5 mg/kg) or saline, gavaged on days 0 and 1 for treatment. Two days after induction of colitis, rats were sacrificed and the end part of their colons were resected for macroscopic and microscopic evaluation and molecular measurement. Sodium selenite improved macroscopic and microscopic view of the colon, decreased cryptitis, crypt abscess and inflammatory cells infiltration and partly maintained mucosal structure. Sodium selenite markedly reduced tissue levels of malondialdehyde (MDA), TNF-α and interferon γ (INF-γ) and decreased myeloperoxidase (MPO) activity. Treatment with sodium selenite also significantly downregulated IL17, IL22, indoleamine 2,3-dioxygenase (IDO1), and kynurenine levels. Western blotting revealed that sodium selenite prevented apoptosis by increasing bcl2/Bax ratio. Furthermore, our findings showed that sodium selenite significantly downregulated the upstream inflammatory molecules such as nuclear factor kappa B (NF-κB) and toll-like receptor 4 (TLR4) in colitis. These findings show that sodium selenite alleviates inflammatory response and oxidative stress and protects against colitis.

Effects of vitamin D treatment on the heart tissue and adropin levels in thyrotoxicosis rats

Background/Aim: Thyrotoxicosis is a hypermetabolic disease, common in people with iodine deficiency. Cardiac pathologies can be seen in untreated cases. Vitamin D is a supportive therapy for thyrotoxicosis and its deficiency also plays an important role in pathologies including cardiac diseases. Adropin is a peptide hormone regulating the energy homeostasis, and its levels in blood change in cardiac pathologies. Our purpose is to reveal the effects of vitamin D treatment on the heart tissue of rats with thyrotoxicosis and on the adropin levels. Methods: Our study was designed as 25 days. 28 Sprague-Dawley female rats were divided into 4 groups; Control (3ml of distilled water), Thyrotoxicosis (100μg/day L-thyroxine) Treatment (100μg/day L-thyroxine+200IU /day Vit. D), Vit D (200IU/day Vit. D). Firstly, heart tissues were stained with Masson trichrome method. The preparations were examined under the microscope and evaluated semi-quantitatively. After that, serum adropin levels were measured with ELISA method. Malondialdehyde level of heart tissue was evaluated by spectrophotometry. Heart tissue was evaluated in aspects of fibrosis, congestion, edema and impairment of tissue integrity. Results: All of the evaluation parameters of the heart tissue were found highly significantly increased in thyrotoxicosis group, in contrast to the control and vitamin D group. Despite a decrease in the treatment group, there was no significant difference in the thyrotoxicosis group (P<0.001). Serum adropin levels of all groups were found to be decreased in contrast to the thyrotoxicosis group. Similarly, tissue MDA levels were significantly higher in the thyrotoxicosis group compared to the other groups. Conclusion: Consequently, heart tissue damage and differences in adropin levels were found in rats with thyrotoxicosis. It was observed that supportive vitamin D treatment helps to regulate these effects.

Chlorogenic acid ameliorates torsion/detorsion-induced testicular injury via decreasing endoplasmic reticulum stress

Testicular torsion (TT) is an urological emergency situation especially in adolescents and young men. The main pathophysiology of testicular torsion/detorsion (T/D) is ischemia-reperfusion (I/R) injury. I/R induces the production of reactive oxygen species (ROS) thought to play a critical role in tissue injury. Increasing evidence suggests that ER stress may play an important role in I/R-induced cell death. During ischemia, oxygen and glucose deprivation also causes abnormalities in protein folding processes. Antioxidants suppress oxidative stress directly as well as ER stress and thus gain importance in the treatment of pathologies associated with oxidative stress and ER stress, such as I/R damage. Chlorogenic acid (CGA) which is formed by the esterification of caffeic and quinic acids and is one of the most abundant phenolic acids in nature. There is also a growing body of studies reporting protective effects of CGA against I/R injury in different tissues, including intestinal, heart and brain. To investigate the effects of CGA on oxidative stress and ER stress in an experimental testicular I/R injury model. Rats were divided into three groups: control, T/D, and T/D+CGA. In the T/D+CGA group, 100mg/kg CGA was given intraperitoneally 30min before detorsion. While tissue malondialdehyde (MDA) levels were determined manually using a colorimetric method, tissue superoxide dismutase (SOD), 78-kDa glucose regulatory protein (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP) levels were determined enzyme-linked immunosorbent assay (ELISA) kits. Johnsen's testicle scoring system was used for histological evaluation. In T/D group, tissue MDA, GRP78, ATF6 and CHOP levels were significantly higher than control group (p<0.05). These increases were significantly reversed with CGA pre-treatment (p<0.05). The histopathological Johnsen score was significantly lower in the T/D group compared to the control group, but the level of histopathological Johnsen score was significantly restored by CGA pre-treatment (p<0.05). The relationship between I/R injury and ER stress has been emphasized frequently in recent years. This study in which the effects of CGA on TT were examined for the first time, showed that CGA can inhibit I/R-induced testicular damage. These results may provide a new insight into CGA and may form the first clinical theoretical basis for the possible use of CGA in the treatment of TT in the future. However, the real function of CGA in TT patients needs further investigation.

Therapeutic potential of essential oil of Melaleuca quinquenervia (Myrtaceae) in a rat model of ethanol-induced peptic ulcer

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To evaluate the effects of M. quinquenervia extract on ethanol-induced peptic ulcer in rats.&#x0D; Methods: The following three groups of (n = 6) Sprague Dawley rats were included in this study: vehicle (C), ethanol-administered (E) and ethanol + M. quinquenervia-treated (MQ). MQ group rats received 100 μg/mL M. quinquenervia essential oil just before 96 % ethanol induction (1 ml/kg). One hour after ulcer induction, the animals were euthanized, and gastric and duodenal tissues were removed. Tissue samples were analysed for myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO) activity, malondialdehyde (MDA) and glutathione (GSH) levels, and histopathological examinations were performed by light microscopy.&#x0D; Results: Gastric and duodenal GSH levels that decreased in the ethanol-administered ulcer groups (p &lt; 0.001), rose following MQ treatment (p &lt; 0.5). Moreover, elevated MPO and MDA levels (p &lt; 0.5) in gastric tissues decreased after MQ-treatment. Similarly, the MQ-treated group showed recovery and control-like morphology compared to the ethanol group in both gastric and duodenal tissues when examined by microscopy.&#x0D; Conclusion: The results indicate that M. quinquenervia extract has a positive impact on gastric injury in rats due to its antioxidant activity. Thus, the plant has a potential for the clinical management of gastric ulcer.&#x0D; &#x0D; &#x0D; &#x0D;

Attenuation of trichloroacetic acid-induced hepatocellular carcinoma by Artemisia judaica ethanolic extract in male rats

BackgroundThe liver cancer is one of the most frequent solid organ malignancies worldwide. Alternative medicine is deemed as one approach that may progress anticancer drugs efficacy and minimize their toxic effects. Similarly, this study was designed to establish the ethanolic extract from Artemisia judaica (AJ) plant and characterize extract that formed using gas chromatography–mass spectrometry analysis, then evaluate their anti-tumour activity alone or in combination with cyclophosphamide(CTX) against trichloroacetic acid (TCA)-induced hepatocellular carcinoma in rats.ResultsThe obtained results revealed that a significant elevation in serum transaminases (ALT, AST), and alkaline phosphatase activities, as well as total serum bilirubin (T.Bil) levels, was recognized in TCA injected rats compared with the control group. In contrast, a significant decrease in liver antioxidant enzymes superoxide dismutase and catalase activities, as well as reduced glutathione level was observed in TCA treated rats compared with the control group. Furthermore, administration of AJ alone or in combination with CTX in rats presented a significant amelioration in all mentioned parameters and attenuated the increased malondialdehyde level in liver tissues compared to the TCA group.ConclusionsIt could be suggested that AJ hepatoprotective effect against chemical-induced hepatocarcinogenesis in combination with chemotherapy drug by reducing chemotherapy side effects confirmed by haematoxylin and eosin stain (H&E) observations, improvement of oxidative stress biomarkers, and liver enzymes.

Ursolic acid mitigates cognitive dysfunction through amelioration of oxidative stress, inflammation and apoptosis in diabetic rats

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To determine the effect of ursolic acid (UA) on diabetes-induced cognitive defect, as well as its mechanism of action in streptozotocin (STZ)-induced diabetic rats.&#x0D; Methods: A rat model of diabetes was established by administration of STZ. The rats received UA via gastric perfusion for 56 successive days. Learning and memory functions were assessed using Morris water maze. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in hippocampus tissues were determined spectrophotometrically. Tumor necrosis factor-a (TNF-a), interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were assayed by quantitative real-time polymerase chain reaction (qRT- PCR) and enzyme-linked immunosorbent assay (ELISA). The protein expression levels of nuclear factor erythroid-2-related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), Bcl-2 and Bax were evaluated by western blotting.&#x0D; Results: Learning and memory impairment in STZ-induced diabetic rats was mitigated by UA (p &lt; 0.05). In hippocampus tissue, UA reduced oxidative stress by enhancing SOD activity and reducing MDA levels. Furthermore, UA reduced inflammatory response by downregulating TNF-α, IL-1β and IL-6 levels (p &lt; 0.05). Concomitantly, the lower protein concentrations of Nrf-2 and HO-1 were elevated by administration of UA. Furthermore, UA suppressed Bax/Bcl-2 ratio to ameliorate apoptosis (p &lt; 0.05).&#x0D; Conclusion: UA reduces diabetes-induced hippocampal oxidative stress, inflammation and apoptosis. Thus, it might be a potential drug candidate for delaying diabetes-associated cognitive decline (DACD).&#x0D; &#x0D; &#x0D; &#x0D;

Gibberellic acid-induced hepatorenal dysfunction and oxidative stress: Mitigation by quercetin through modulation of antioxidant, anti-inflammatory, and antiapoptotic activities.

The plant growth regulator gibberellic acid (GA3) is widely used in agriculture in many countries. However, little is known about its danger to human health or its physiologic and biochemical pathways. Our study examined the effect of GA3 on liver and kidney function and the effect of quercetin on the hepatorenal toxicity induced by GA3 in four groups of male albino rats. For 4weeks, the control group (CNT) received saline, the quercetin group (QR) received daily intraperitoneal injections of quercetin (50mg/kg/BW) dissolved in saline, the gibberellic acid group (GA3) received GA3 (55mg/kg/BW) via oral gavage, and the protective group (QR) was injected with quercetin and gavaged with GA3 in the same doses used in the QR and GA3 groups (50mg/kg/BW +GA3 and 55mg/kg/BW). GA3 induced liver and kidney injury, as shown by elevated serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase,and gamma-glutamyl transferase (GPT, GOT, and GGT) as well as increased levels of creatinine, urea, and uric acid. Hepatorenal toxicity was demonstrated by a significant increase in levels of serum and tissue malondialdehyde (MDA) and decreased antioxidant enzyme activity, such as catalase (CAT) and superoxide dismutase (SOD), accompanied by a subsequent decrease in glutathione peroxidase (GPx) levels in liver and kidney tissue of GA3-treated rats. Administration of quercetin (QR) significantly protected hepatorenal tissue against the toxic effect of GA3 through normalization of the hepatic and renal function markers. It also retrieved the antioxidant ability by modulating the hepatorenal toxic effect at the molecular level through upregulation of antiapoptotic genes and downregulation of transforming growth factor-β1 (TFG-β1), cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB). Impairment of liver and kidney function was confirmed by histologic and immunohistochemical analyses. Pretreatment with quercetin was effective at attenuating histopathologic changes in hepatic and renal tissues by regulating the immunoexpression of caspase-3 and Bcl-2 to return them to more normal values. PRACTICAL APPLICATIONS: The confirmed hepatorenal dysfunction caused by GA3 was ameliorated by quercetin administration. Moreover, quercetin demonstrated the potential to reverse hepatorenal dysfunction by regulating inflammatory and antioxidant properties, inhibiting the production of free radicals and inflammation-associated cytokines, and modulating antioxidants and antiapoptotic activity.

Protective effect of melatonin as an antioxidant in the intestine of rats with superior mesenteric arterial occlusion.

The superior mesenteric artery is a branch of the aortic artery that supplies blood to the small and some parts of the large intestine. Any obstruction in blood flow and reperfusion causes tissue damage in the intestine. This study aimed to determine the rate of fat peroxidation and tissue protein as an indicator of tissue degradation after ischemia and reperfusion following induction of superior mesenteric artery occlusion in the intestine and to evaluate the protective effect of melatonin as a free radical scavenger and antioxidants in rats. In this study, 36 male Wistar-Albino rats weighing between 80-120 g were equally divided into six groups and received different melatonin doses (10, 20, and 30 mg/kg) intramuscularly. In this regard, Group 1 was the control group, Group 2 was the Sham group (underwent surgery to dissect the upper mesenteric artery and injected the same volume of solvent), Group 3 was Ischemia-reperfusion (IR), Group 4 was IR with melatonin at a dose of 10 mg/kg, Group 5 was IR with melatonin at a dose of 20 mg/kg, and Group 6 was IR with melatonin at a dose of 30 mg/kg. The results showed that the level of tissue malondialdehyde (MDA) was significantly lower in groups 4, 5, and 6 than in group 3 (P <0.05). Tissue protein levels were significantly higher in group 4 than in group 3 (P <0.001). Tissue protein levels in groups 5 and 6 did not significantly differ from group 3 (P = 0.191). Overall, this study showed that melatonin at a dose of 10 mg/kg has an antioxidant effect preventing induced damage due to superior mesenteric artery occlusion.

Reducing effects of ginkgo biloba (egb761) extract on skeletal muscle ischemia-reperfusion injury in rats

Aim: The restoration of circulation following a period of ischemia results in the release of the metabolites that accumulate in the ischemic tissue into circulation with untoward effects on the organs. Many studies have been conducted to date into the prevention of such ischemia-reperfusion injuries. Ginkgo Biloba extract is known to have antioxidant effects, although there is a lack of data on its effects on a skeletal muscle ischemia-reperfusion model. The present study investigates the use of Ginkgo biloba extract (egb761) for the reduction of experimentally-induced skeletal muscle ischemia-reperfusion injury. Material and Methods: A total of 32 Sprague-Dawley rats were divided into four groups as follows: Group 1 (n=8), control group; Group 2 (n=8), limb ischemia model; Group 3 (n=8), ischemia-reperfusion model; and Group 4 (n=8), Ginkgo biloba group. After the models were created in each group, soleus muscle, lung and liver tissues were removed. Tissue malondialdehyde (MDA) levels were measured biochemically to demonstrate lipid peroxidation. The percentage of viable cells in the soleus muscle was calculated through a histochemical examination. Results: The comparison of soleus muscle MDA levels revealed no statistically significant difference between Group 1 and Groups 2 and 3, whereas the levels were significantly lower in Group 1 than those in Group 4 (p&lt;0.05). Similarly, there was a significant reduction in Group 4 than in Group 3 (p&lt;0.05). The analysis of lung tissue MDA levels revealed no significant difference between Group 1 and Group 2, whereas MDA levels were significantly increased in Group 3 than in Group 1 (p&lt;0.05), while there was no difference between Group 1 and Group 4. The analysis of liver tissue MDA levels showed significantly increased levels in Groups 3 and 4 than in Group 1 (p&lt;0.05). The percentage of viable cells was significantly decreased in Groups 2 and 3 than in Group 1 (p&lt;0.05). There was a significant reduction in Group 4 than in the control group. Conclusion: The results of the present study suggest that Ginkgo biloba (EGb761) extract may be used to reduce the local and systemic effects occurring after the restoration of blood flow following acute arterial occlusion. There is, however, an apparent need for large-scale, prospective, randomized trials to demonstrate the efficacy of Ginkgo biloba treatment.

Effect of MCI-186 on Lipid Peroxidation in Experimental Traumatic Brain Damage in Rats.

Brain damage occurs in many clinical conditions, including trauma, ischemia, and hypertension. Reactive oxygen products and lipid peroxidation are responsible for the brain damage that occurs in these clinical conditions. We investigated whether MCI-186 (3-methyl-1-phenyl-2-pyrazoline-5-one), a free radical binding agent on lipid peroxidation, affects malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GPx) levels in traumatic brain damage. The traumatic brain damage model, modified by Feeney, was performed on 28 male Wistar rats separated into 4 groups. The MDA, GSH, and GPx levels in the brain tissues of each group were studied. MDA levels in the traumatized group were significantly higher than those in the sham and MCI-186 groups (p<0.05), while GSH levels were significantly higher in the sham group than in the trauma and solvent groups (p<0.05). No significant difference was observed between the sham and MCI-186 groups (p>0.05). Although the average GPx level was higher in the sham and MCI-186 groups, no significant difference was found between groups. Reactive oxidation products significantly decreased in the MCI-186 group. Thus, MCI-186 can be used as a free radical-binding agent in traumatic brain damage.

Reproductive effects of Abelmoschus esculentus fruit methanol extract in female Wistar rats.

Current researches aim at identifying modifiable risk factors for infertility, particularly dietary lifestyle. Abelmoschus esculentus is one of the important vegetables in the human diet with reported valuable nutrients but has been linked with reproductive dysfunction in males. This study investigated the reproductive effects of Abelmoschus esculentus fruit methanol extract in female Wistar rats. Dried Abelmoschus esculentus fruit was extracted with methanol. Fifteen female Wistar rats (180–200 g) grouped into three (n = 5) received 1.0 mL/kg/day distilled water (control), 70 and 200 mg/kg/day of the extract once daily for 21 days via oral gavage. The estrous cycle was assessed using Marcondes and Papanicolaou methods. The histology of the tissues was evaluated by microscopy. Serum follicle-stimulating hormone, luteinizing hormone, and estrogen levels were measured using an enzyme-linked immunosorbent assay. Tissue antioxidant activities and malondialdehyde levels were assayed by spectrophotometry. Data were analyzed using the Analysis of variance at a significance of p < 0.05. The estrous cycle of the Abelmoschus esculentus fruit methanol extracts treated rats showed normal cellular characteristics. Though Abelmoschus esculentus fruit methanol extract increased the antioxidant activities, it reduced the body weight and follicle-stimulating hormone level and caused severe inflammation and fibrosis of the ovary and uterus. Abelmoschus esculentus fruit methanol extract adversely altered the reproductive functions of female Wistar rats by disrupting the ovarian and uterine cytology and reducing hormone levels.

Cerebrolysin Amelioration of Spinal Cord Ischemia/ Reperfusion Injury in Rabbit Model.

Cerebrolysin is a well-known neuroprotective agent. This study investigated its effects on inflammation, oxidative stress, apoptosis, and neurologic recovery in the setting of spinal cord ischemia/reperfusion injury (SCIRI) in an experimental animal model. Rabbits were randomly divided into five groups: control, ischemia, vehicle, methylprednisolone (30 mg/kg), and cerebrolysin (5 ml/kg) group. The rabbits in the control group underwent laparotomy; the other groups underwent spinal cord ischemia and reperfusion injury for 20 min. Neurologic examination after 24 h was based on the Modified Tarlov scale. Myeloperoxidase activities, catalase and malondialdehyde levels, and caspase-3 concentrations were determined in serum and tissue samples. Serum xanthine oxidase levels were studied and histopathological and ultrastructural changes were examined. After SCIRI, serum and tissue myeloperoxidase activities, malondialdehyde levels, caspase-3 concentrations, and serum xanthine oxidase activities were increased (p 0.01-0.001). Catalase levels were significantly diminished (p 0.001). Cerebrolysin treatment correlated with reduced myeloperoxidase and xanthine oxidase activities, malondialdehyde levels and caspase-3 concentrations; and with increased catalase levels (p 0.001, for all). The cerebrolysin group showed improved histopathological, ultrastructural, and neurological outcomes. For the first time in the literature the current study reports anti-inflammatory, antioxidant, antiapoptotic, and neuroprotective effects of cerebrolysin in a SCIRI rabbit model.

Effect of formononetin from Trifolium pratense L. on oxidative stress, energy metabolism and inflammatory response after cerebral ischemia-reperfusion injury in mice

Cerebral ischemia-reperfusion injury (CIRI) is one of the main diseases leading to death and disability. Studying the role and mechanism of drugs in mitigating CIRI is of great significance. In the present study, the effect of formononetin from Trifolium pratense L. on oxidative stress, energy metabolism impairment and inflammatory response after cerebral ischemia-reperfusion injury (CIRI) in mice were investigated. Formononetin was extracted from Trifolium pratense L. and was purified. The mice were treated with formononetin for six days. Then, the CIRI model was established. After 24 h of reperfusion, compared with model group, in formononetin group, the neurological deficit score, cerebral water content and cerebral infarction rate were significantly decreased, the brain tissue nitric oxide and malondialdehyde levels were significantly decreased, the brain tissue superoxide dismutase level was significantly increased, the brain tissue Na+-K+-ATPase, Ca2+-Mg2+-ATPase and Ca2+-ATPase activities were significantly increased, and the brain tissue tumor necrosis factor α, interleukin 1β and interleukin 6 levels were significantly decreased. In conclusion, formononetin from Trifolium pratense L. can reduce the oxidative stress, energy metabolism impairment and inflammatory response in brain tissues, thus mitigating the CIRI in mice.

Extraction of lycopene from tomato pomace and its protective effects on renal injury in diabetic rats

The aim of this study was to investigate the protective effects of lycopene from tomato pomace on renal injury in diabetic rats. Lycopene was extracted from tomato pomace. The rats were divided into control, model and 10, 20 and mg/kg lycopene groups. The diabetic nephropathy model was constructed in the latter four groups. Then, the latter three groups were treated with 10, 20 and mg/kg lycopene, respectively. After four weeks of treatment, compared with the model group, in 20 and 40 mg/kg lycopene groups the serum fasting plasma glucose level was decreased (P < 0.05), the fasting insulin level was increased (P < 0.05), the renal index and 24-h urinary protein level were decreased (P < 0.05), the blood urea nitrogen and serum creatinine levels were decreased (P < 0.05), the renal tissue superoxide dismutase and glutathione peroxidase levels were increased (P < 0.05), the renal tissue malondialdehyde level was decreased (P < 0.05), and the serum tumor necrosis factor α, interleukin 6 and hypersensitive C-reactive protein levels were decreased (P < 0.05). In conclusion, lycopene from tomato pomace can alleviate renal injury in diabetic rats. The mechanism may be related to the resistance of oxidative stress and inflammatory response.

Doxycycline hyclate stimulates inducible nitric oxide synthase and arginase imbalance, potentiating inflammatory and oxidative lung damage in schistosomiasis

BackgroundWe investigated the relationship between inducible nitric oxide synthase (iNOS) and arginase pathways, cytokines, macrophages, oxidative damage and lung granulomatous inflammation in S. mansoni-infected and doxycycline-treated mice. MethodsSwiss mice were randomized in four groups: (i) uninfected, (ii) infected with S. mansoni, (iii) infected + 200 mg/kg praziquantel (Pzt), (iv) and (v) infected + 5 and 50 mg/kg doxycycline. Pzt (reference drug) was administered in a single dose and doxycycline for 60 days. ResultsS. mansoni-infection determined extensive lung inflammation, marked recruitment of M2 macrophages, cytokines (IL-4, IL-5, IFN-γ, TNF-α) upregulation, intense eosinophil peroxidase (EPO) levels, arginase expression and activity, reduced iNOS expression and nitric oxide (NO) production. The higher dose of doxycycline aggravated lung granulomatous inflammation, downregulating IL-4 levels and M2 macrophages recruitment, and upregulating iNOS expression, EPO, NO, IFN-γ, TNF-α, M1 macrophages, protein carbonyl and malondialdehyde tissue levels. The number and size of granulomas in doxycycline-treated animals was higher than untreated and Pzt-treated mice. Exudative/productive granulomas were predominant in untreated and doxycycline-treated animals, while fibrotic/involutive granulomas were more frequent in Pzt-treated mice. The reference treatment with Pzt attenuated all these parameters. ConclusionOur findings indicated that doxycycline aggravated lung granulomatous inflammation in a dose-dependent way. Although Th1 effectors are protective against several intracellular pathogens, effective schistosomicidal responses are dependent of the Th2 phenotype. Thus, doxycycline contributes to the worsening of lung granulomatous inflammation by potentiating eosinophils influx and downregulating Th2 effectors, reinforcing lipid and protein oxidative damage in chronic S. mansoni infection.

Changes in heavy metal levels, reproductive characteristics, oxidative stress markers and testicular apoptosis in rams raised around thermal power plant

Male reproductive dysfunction is one of the damages in the organism caused by heavy metals. In this study, it was aimed to investigate the changes in heavy metal levels in serum and testicular tissue, and serum hormone levels, epididymal spermatozoa characteristics, tissue oxidative stress levels, testicular histology and testicular apoptosis level in rams raised in remote and near regions of a thermal power plant. A total of 75 rams were divided into 3 groups according to the regions, where they were born and raised, being far [250 km distance, group 1 (control), n = 25], close (20 km distance, group 2, n = 25) and very close (10 km distance, group 3, n = 25) to the thermal power plant. The blood along with testis and epididymis tissues was taken from the animals after slaughtering. In addition, soil and water heavy metal analyzes were also performed. The highest levels of serum Al, Cr, As, Ag, Sn and testicular Al, V, Ni, Ag, Cd, Cr, As, Pb, and the lowest levels of serum Cu, testicular Cu and Zn were determined in group 3 compared to control. Soil and water heavy metal results were similar to those found in serum and testis. The lowest serum testosterone level, tissue glutathione-peroxidase and catalase activities, spermatozoon concentration, and the highest tissue malondialdehyde level, dead spermatozoon rate, Bax apoptotic protein expression level and Bax/Bcl-2 rate alongside some testicular histopathological lesions were found in group 3 in comparison to control. Significant correlations were determined between some heavy metal levels and some parameters measured. As a result, heavy metals accumulate in the soil and water in the region close to the thermal power plant. The endocrine and exocrine reproductive potentials of rams born and grown in these regions were clearly damaged by the increased testicular heavy metals due to water drank and herbs consumed.

Investigation of the Effects of L-carnitine and magnesium on Oxidative Stress and Cytokines in the Tissue of Experimental diabetic rats

Abstract The aim of this study was to determine the effects of L-carnitine and magnesium on the levels of tissue malondialdehyde, 8-hydroxy-2’-deoxyguanosine, and cytokines (tumor necrosis factor alpha, interleukin-6) in streptozotocin-induced experimental diabetes in rats. Eighty male Wistar albino rats (200-250 g) were divided into 8 groups with 10 rats in each group. The groups received the following treatments: Control group; 2 ml distilled water (by gavage); Group 2: 50 mg/kg (b.w.) i.p. streptozotocin; Group 3: 125 mg/kg (b.w.) magnesium; Group 4: 300 mg/kg (b.w.) L-carnitine; Group 5: 125 mg/kg (b.w.) magnesium +300 mg/kg (b.w.) L-carnitine; Group 6: 50 mg/kg (b.w.) streptozotocin +125 mg/kg (b.w.) magnesium; Group 7: 50 mg/kg (b.w.) streptozotocin +300 mg/kg (b.w.) L-carnitine and Group 8: 50 mg/kg (b.w.) streptozotocin +125 mg/ kg (b.w.) magnesium+300 mg/kg (b.w.) L-carnitine administered for 4 weeks. Liver and kidney malondialdehyde, 8-hydroxy-2’-deoxyguanosine, tumor necrosis factor alpha and interleukin-6 levels did not change in the magnesium, L-carnitine, and magnesium + L-carnitine groups compared to the control. The highest levels of malondialdehyde, 8-hydroxy-2’-deoxyguanosine, tumor necrosis factor alpha and interleukin-6 were determined only in the group with diabetes (Group 2). Lipid peroxidation, DNA damage, and cytokine levels were significantly reduced in diabetic animals with the administration of magnesium and L-carnitine separately or in combination. Based on the obtained results it can be concluded that magnesium and L-carnitine may have antidiabetic effects, especially in combination.

Cattle manure compost and biochar supplementation improve growth of Onobrychis viciifolia in coal-mined spoils under water stress conditions

Surface mining is a critical anthropogenic activity that significantly alters the ecosystem, while the use of appropriate revegetation techniques can be considered an important and feasible strategy in the way to improve the ecosystem services of degraded land. In the present study, we carried out a pot experiment to investigate the effects of three different variables on morpho-physiological and biochemical parameters of Onobrychis viciifolia to assess the capability of this species to be used for restoration purposes. Specifically, the variables studied were: (a) water (W) regime, working at five values as regards field capacity (FC) (i.e., 80% FC = highest, 72% FC = high, 60% FC = moderate, 48% FC = low, and 40% FC = very-low dose); and (b) rates of cattle manure compost (CMC) and wood biochar (BC) (weight/weight ratio), working at five rates (i.e., 4.0% = highest, 3.2% = high, 2.0% = moderate, 0.8% = low, and 0% = either no-CMC or no-BC dose). In addition, soil physical-chemical properties and enzyme activities were also investigated at the end of the experimental period. It was found that morphological growth attributes such as plant height, maximum root length, and dry biomass significantly increased with W, CMC and BC applications. Compared to control, moderate-to-high W, CMC and BC doses (W80CMC2BC2) increased net photosynthesis rate (by 42%), stomatal conductance (by 50%), transpiration rate (by 29%), water use efficiency (by 10%), chlorophyll contents (by 73%), carotenoid content (by 81%), leaf relative water content (by 33%) and leaf membrane stability index (by 30%). Under low-W content, the application of CMC and BC enhanced osmotic adjustments by increasing the content of soluble sugar and the activities of superoxide dismutase, catalase, peroxidase and ascorbate peroxidase, decreasing the oxidative stress, as verified by low levels of hydrogen peroxide, superoxide anion, malondialdehyde and proline contents in leaf tissues. Moreover, application of W, CMC and BC significantly improved soil water holding capacity, available nitrogen, phosphorus and potassium, urease and catalase activities, which facilitate plant growth. These results would aid in designing an appropriate strategy for achieving a successful revegetation of O. viciifolia, providing optimum doses of W (64% field capacity), CMC (2.4%) and BC (1.7%), with the final aim of reaching ecological restoration in arid degraded lands.

Protecting Effects of N-acetyl Cysteine Supplementation Against Lead and Cadmium-Induced Brain Toxicity in Rat Models

We aimed to investigate mitigating effects of N-acetylcysteine (NAC) on the oxidative stress, apoptosis and Parkinson's disease (PD)-related genes in the brain tissue of male rats exposed to continuous doses of cadmium and lead. Rats were randomly divided into five groups, including G1 (control), G2 (continuous dose of Cd), G3 (continuous dose of Pb), G4 (continuous dose of Cd + NAC), and G5 (continuous dose of Pb + NAC). Biomarkers of oxidative stress, malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured. Expression of PD- and apoptosis-related genes was considered using RT-PCR. Chronic exposure to these heavy metals was associated with accumulation of Pb and Cd in the brain and blood and caused severe morphological changes in the brain, as well as decreased body and brain weights. Continuous exposure to Cd and Pb significantly decreased TAC content and SOD expression but increased MDA level in the brain tissues (P < 0.001). A significant increase was observed in expression of PD-related genes, Parkin, Pink1, LRRK2, SNCA, and Caspase-3 in the brain tissues following exposure to Cd and Pb. Pb exhibited stronger toxicity on the brain tissue compared to Cd. NAC supplementation not only improved morphological changes, but also compensated antioxidant capacity and expression of apoptosis- and PD-related genes in the brain tissues when compared to rats exposed to Pb and Cd alone. Chronic exposure to Pb and Cd is strongly associated with accumulation of these heavy metals in the brain, morphological changes, antioxidants depletion, oxidative stress, and brain cells apoptosis. Changes in expression of PD-related genes indicate the higher risk of PD among individuals who are chronically exposed to these heavy metals. NAC can protect brain tissue against Pb and Cd toxicity by elevating antioxidants capacity, mitigating oxidative stress, apoptosis, and down-regulating of PD-related genes.

Inhibition of miR-218-5p reduces myocardial ischemia–reperfusion injury in a Sprague-Dawley rat model by reducing oxidative stress and inflammation through MEF2C/NF-κB pathway

Following myocardial ischemia, myocardial reperfusion injury causes oxidative stress (OS) and inflammation, leading to myocardial cell apoptosis and necrosis. Recently, emerging studies have shown that microRNAs (miRNAs) contribute to the pathophysiology associated with myocardial ischemia–reperfusion (I/R). In this study, we conducted both in-vitro and in-vivo experiments to explore the role of miR-218-5p in ischemia–reperfusion (I/R)- or oxygen and glucose deprivation/reperfusion (OGD/R)-mediated cardiomyocyte injury. A total 44 Sprague-Dawley (SD) rats were used, and randomly divided into four groups, control group (n = 11), miR-218-5p-in group (n = 11), I/R group (n = 11), I/R + miR-218-5p-in group (n = 11). Our data showed that miR-218-5p was overexpressed in H9C2 cardiomyocytes under OGD/R treatment. miR-218-5p inhibition reduced the lactate dehydrogenase (LDH) activity and the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expression of tumor necrosis factor alpha (TNF-α), interleukin (IL-1β), and IL-6. Oppositely, miR-218-5p overexpression aggravated OGD/R-mediated damage on H9C2 cells, whereas nuclear factor kappa B (NF-κB) pathway inhibition or myocyte enhancer factor 2C (MEF2C) upregulation reversed miR-218-5p mimics-mediated effects. Bioinformatics analysis predicted that miR-218-5p targeted and dampened its expression, which was testified by the dual-luciferase reporter assay and RNA pull-down assay. In vivo, inhibiting miR-218-5p declined LDH activities and ROS, MDA and SOD levels in rat myocardial tissues under I/R injury, alleviated myocardial fibrosis and inflammatory reactions, and reduced myocardial infarction area. Overall, inhibition of miR-218-5p choked oxidative stress and inflammation in myocardial I/R injury via targeting MEF2C/NF-κB axis, thus relieving the disease progression.