The effects of olibanum on male reproductive system damage in a lipopolysaccharide induced systemic inflammation model in rat.

Background: Lipopolysaccharide (LPS) as a particle of Gram-negative bacteria is a main contributer in the pathogenesis of the male reproductive system infectious. Male infertility due to LPS is reported to be related to overproduction reactive oxygen species. This study aimed to investigate the effects of olibanum on oxidative stress and apoptosis in testes and sperm dysfunction induced by LPS. Methods: The male (n = 28) rats were allocated in four groups: control, LPS (1 mg/kg, i.p., 14 days), LPS + Olibanum 100 (100 mg/kg, i.p., 14 days), and LPS + Olibanum 200 (200 mg/kg, i.p., 14 days). Germ cell apoptosis was determined by TUNEL assays and computed using the stereological method. Additionally, semen samples of the animals were analyzed for sperm count and morphology. Oxidative stress indicators were also determined. Results: The count of TUNEL-positive germ cells in LPS-treated rats was more than that in the controls. Treatment of the animals with olibanum significantly attenuated the number of apoptotic cells compared to the LPS group. The sperm count and those with a normal morphology in LPS-treated rats was lower than that in the controls. Administration of olibanum significantly improved the sperms with normal morphology and sperm count. Olibanum treatment also improved superoxide dismutase, catalase, and total thiol in testicular tissue and decreased malondialdehyde. Conclusion: Administering both doses of olibanum in LPS-treated rats had potentially a therapeutic value in reducing germ cell apoptosis, as well as improving sperm parameters.

Therapeutic effects of Medicago sativa against cyclophosphamide-induced toxicity in rats.

Objective: Medicago sativa (M. sativa) has been traditionally used for treating anemia; therefore, M. sativa hydro-ethanolic extract therapeutic effects against cyclophosphamide (CP) -induced hematologic and liver toxicity were examined. Materials and Methods: Thirty male Wistar rats were randomly divided to control (saline); CP (100 mg/kg, day 1-3, subcutaneously); CP+ M. sativa 200 mg/kg (MS 200); CP+ M. sativa 400 mg/kg (MS 400); CP+ dexamethasone (0.1 mg/kg), (all groups n=6). Treated animals received M. sativa or dexamethasone by gavage from days 7-14. On days 0, 7, and 14, hematologic parameters, and on the 14th day, serum and liver tissue oxidative stress markers including nitric oxide, malondialdehyde (MDA) and total thiol levels, superoxide dismutase (SOD) and catalase (CAT) activities, serum lipids, and liver enzymes were measured. Results: Animal weight, platelet, white blood cells, and red blood cells counts, hemoglobin and hematocrit as well as thiol, SOD, and CAT activities in serum and liver tissue were significantly reduced, but serum nitric oxide, MDA, total cholesterol, triglycerides, low-density lipoproteins levels, and liver enzymes were increased in the CP group compared to the control group (p<0.05 to p<0.001). Administering M. sativa extract (400 mg/kg) significantly enhanced platelet count, and SOD and CAT activities and inhibited all of the CP toxic effects, while dexamethasone improved platelet count and oxidative stress markers compared to the CP group (p<0.05 to p<0.001). Conclusion: The extract of M. sativa (400 mg/kg) showed therapeutic effects against the CP-induced myelosuppression and thrombocytopenia and improved oxidative stress markers which were comparable to the effect of dexamethasone.

Unveiling the Effects of Left Hemispheric Intracerebral Hemorrhage on Long-term Potentiation and Inflammation in the Bilateral Hippocampus: A Preclinical Study.

OBJECTIVE: Changes in cognition and memory are common complications of intracerebral hemorrhage (ICH), although the exact cause of this phenomenon is still unknown. The objectives of our project were to assess the changes in long-term potentiation, inflammation, and cell damage in the bilateral hippocampus following striatal intracerebral hemorrhage at different time points. MATERIALS AND METHODS: Unilateral ICH was induced in the striatum of 96 Wistar rats (6 control groups and 6 ICH groups). We measured changes in synaptic inputs in the bilateral hippocampus using the field potential recording method on days 3, 7, and 14 after ICH. After staining the section with hematoxylin, the volume and number of hippocampal cells were measured. The number of NF-κB positive cells was evaluated using the immunohistochemistry method. RESULTS: There was a significant change in the amplitude and slope of the hippocampal excitatory potential in the ICH group compared to the sham group, but only on the 7th day after surgery. Specifically, the ipsilateral hippocampus in the ICH-7 group showed an increase in stimulation recording in 90 minutes compared to the sham-7 group (p<0.0001), while the contralateral hippocampus in the ICH-7 group exhibited a decrease in potential recording compared to the sham-7 group (p<0.0001). By day 14, the ICH group had a lower cell density in both the ipsilateral (p<0.05) and contralateral hippocampus (p<0.05) compared to the sham group, but there was no significant change in the hippocampal volume between the groups at any time interval. Furthermore, our immunohistochemical analysis revealed that the number of NF-kB-positive cells in both hemispheres of the ICH groups was significantly greater than that of the sham groups across all time intervals. CONCLUSIONS: These findings suggest that striatal injury may lead to inflammation and cell death in the bilateral hippocampus, which can impair cognitive function after ICH.

Protective effects of hydro-alcoholic extract of Zataria multiflora on lipopolysaccharide-induced inflammation and oxidative stress in rat liver.

Objective: Liver is an important player in regulation of body homeostasis. Study investigated the effects of hydro-alcohol extract of Zataria multiflora (ZM) on oxidative damage, level of IL-6 and enzymes of liver in lipopolysaccharide (LPS)-treated rats. Materials and Methods: The rats were distributed into 5 groups: 1) Control; 2) LPS; and 3-5) ZM-Extract (Ext) 50, ZM-Ext 100, and ZM-Ext 200. ZM-Ext groups received 50, 100 and 200 mg/kg of extract 30 min before LPS. Drugs were injected intraperitoneally. The entire period of this project was 17 days. In first three days, only extract was injected and then, ZM was injected along with LPS. Results: LPS increased the level of ALT (Alanine aminotransferase), AST (Aspartate aminotransferase ), ALK-P (Alkaline Phosphatase), IL-6, malondialdehyde (MDA), and nitric oxide (NO) metabolites and lowered thiol, superoxide dismutase (SOD) and catalase (CAT) concentration. ZM extract not only reduced ALT, AST, ALK-P, IL-6, MDA, and NO metabolites concentrations but also increased thiol content, and SOD and CAT levels. Conclusion: Extract of ZM prevented LPS-induced hepatotoxicity. This protective effect was associated with reduction in inflammation and oxidative stress.

The effect of olibanum on the rats with memory deficit induced by scopolamine.

BACKGROUND: Oxidative stress is an important contributor to Alzheimer's disease. Olibanum has therapeutic effects on various diseases. The effect of Olibanum on memory deficit induced by scopolamine (Sco) was challenged. METHODS: Four groups were considered as (1) control (2) Sco, (3-4) Sco - Olib 100 and 200 mg/kg. Treatment by Olib or vehicle was done for two weeks. The third week was accompanied by the Morris water maze (MWM) and passive avoidance (PA) with Sco injection. On the last day, the brain and hippocampus were used for evaluation of the malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and a total thiol group. RESULTS: Sco increased the traveled time and distance to reach the hidden platform during five days of learning (p<0.01 - p<0.001) whereas it decreased the traveled time and distance (p<0.05- p<0.01) in the target area during the probe test of MWM. Sco also decreased delay time in the PA test (P<0.05 - P<0.001). Sco also decreased CAT, SOD, and thiol, whereas it, increased MDA in both the cortex and hippocampus (p<0.01 - p<0.001). Olib attenuated the impaired performance of the rats induced by Sco in MWM and PA tests. Olib reversed the increasing effects of Sco on MDA in both cortex and hippocampus and also reversed the attenuating effects of Sco on CAT, SOD, and thiol. CONCLUSION: Olib had an inhibitory effect on memory deficit induced by Sco probably through its anti-oxidant property.

The effects of vitamin D on cardiovascular damage induced by lipopolysaccharides in rats.

Introduction: Inflammation and oxidative stress are contributed to cardiovascular diseases. Vitamin D (Vit D) has antioxidant and anti-inflammatory properties. In the current research, the effect of Vit D on cardiac fibrosis and inflammation, and oxidative stress indicators in cardiovascular tissues was studied in lipopolysaccharides(LPS) injected rats. Methods: Rats were distributed into 5 groups and were treated for 2 weeks. Control: received vehicle(saline supplemented with tween-80) instead of Vit D and saline instead of LPS, LPS: treated by 1 mg/kg of LPS and was given vehicle instead of Vit D, LPS-Vit D groups: received 3 doses of Vit D (100, 1000, and 10000 IU/kg) of Vit D in addition to LPS. Vit D was dissolved in saline supplemented with tween-80 (final concentration 0.1%) and LPS was dissolved in saline. The white blood cell (WBC) was counted. Oxidative stress markers were determined in serum, aorta, and heart. Cardiac tissue fibrosis was also estimated using Masson's trichrome staining method. Results: WBC and malondialdehyde (MDA) were higher in the LPS group than the control group, whereas the thiol content, superoxide dismutase (SOD), and catalase (CAT) were lower in the LPS group than the control group (P<0.01 and P<0.001). Administration of Vit D decreased WBC (P<0.001) and MDA (P<0.05 and P<0.001) while enhanced thiol (dose 10000 IU/Kg) (P<0.001), SOD (dose 10000 IU/kg) (P<0.001), and CAT (P<0.05 and P<0.001) compared to the LPS group. All doses of Vit D also decreased cardiac fibrosis compared to the LPS group (P<0.001). Conclusion: Vit D protected the cardiovascular against the detrimental effect of LPS. This cardiovascular protection can be attributed to the antioxidant and anti-inflammatory properties of Vit D.

Rosiglitazone attenuates amyloid beta and glial fibrillary acidic protein in the hippocampus and neuroinflammation associated learning and memory impairments in rats.

OBJECTIVE: The aim of the current study was to investigate the beneficial effects of rosiglitazone (Rosi) on amyloid beta(Aß) and glial fibrillary acidic protein (GFAP) in the hippocampus and neuroinflammation-associated learning and memory impairments in rats. MATERIALS AND METHODS: The rats were grouped and treated as follows: (1) Control in which saline and vehicle were administered instead of LPS and Rosi respectively. (2) Lipopolysaccharide (LPS) group in which LPS was dissolved in saline and injected (1 mg/kg) intraperitoneally. Vehicle was administered instead of Rosi in this group. (3-5) LPS+ Rosi 1, LPS+ Rosi 3, and LPS+ Rosi 5 groups in them 1, 3, or 5 mg/kg of Rosi respectively was administered 30 min before LPS. The treatments were done for two weeks. In the first week, Rosi or its vehicle was injected 30 min before LPS. In the second week, the treatments were the same as the first week and behavioral tests were also carried out in the second week. The hippocampal tissues were finally detached for biochemical assessment. RESULTS: The results showed that Rosi reversed increased levels of Aß, GFAP, interleukin (IL)- 6, tumor necrosis factor-α (TNF-α), nitric oxide (NO) metabolites, and malondialdehyde (MDA) due to LPS injection. Rosi also reversed attenuating effects of LPS on IL-10 and thiol concentration and activities of catalase (CAT) and superoxide dismutase (SOD). In the Morris water maze test, the LPS group had a longer latency to find the platform while spent a shorter time spent in the target quadrant in the probe trial than the control group. In the passive avoidance test, the animals of the LPS group had a shorter delay to enter the dark chamber than the animals of the control group. Treatment with Rosi reversed these parameters. CONCLUSION: The findings showed Rosi attenuated Aß, GFAP, and oxidative stress in the hippocampus and neuroinflammation-associated learning and memory impairments in rats.

Nano-selenium relieved hepatic and renal oxidative damage in hypothyroid rats.

Hypothyroidism can induce oxidative stress. Nano-selenium (Nano Sel) has antioxidant effects. The current research explored Nano Sel effects on hepatic and renal oxidative damage induced by hypothyroidism in rats. Animals were grouped into (1) Control; (2) Propylthiouracil (PTU) group which received water mixed with 0.05% of PTU; (3) PTU-Nano Sel 50; (4) PTU-Nano Sel 100; and (5) PTU-Nano Sel 150. Besides PTU, the PTU-Nano Sel groups were treated with 50, 100, or 150 µg/kg of Nano Sel intraperitoneally. Treatments were done for 6 weeks. The serum level of T4, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), albumin, total protein, creatinine, and blood urea nitrogen (BUN) was evaluated. Malondialdehyde (MDA) and total thiol concentration and the activity of catalase (CAT) and superoxide dismutase (SOD) in hepatic and renal tissues also were checked. Hypothyroidism induced by PTU significantly increased AST, ALT, ALP, creatinine, BUN, and MDA concentration and noticeably reduced albumin, total protein, total thiol level, and SOD and CAT activity. Administration of Nano Sel ameliorated the adverse effects of hypothyroidism on liver and kidney function. Nano Sel applied protective effects against hepatic and renal damage resulting from hypothyroidism via ameliorating the oxidative stress status. More cellular and molecular experiments need to be done to understand the exact mechanisms.

Effect of Allium cepa extract on total and differential WBC, TP level, oxidant and antioxidant biomarkers, and lung pathology in ovalbumin-sensitized rats.

BACKGROUND: Previous studies have shown that Allium cepa (A. cepa) has relaxant and anti-inflammatory effects. In this research, A. cepa extract was examined for its prophylactic effect on lung inflammation and oxidative stress in sensitized rats. METHODS: Total and differential white blood cell (WBC) count in the blood, serum levels of oxidant and antioxidant biomarkers, total protein (TP) in bronchoalveolar lavage fluid (BALF), and lung pathology were investigated in control group (C), sensitized group (S), and sensitized groups treated with A. cepa and dexamethasone. RESULTS: Total and most differential WBC count, TP, NO2, NO3, MDA (malondialdehyde), and lung pathological scores were increased while lymphocytes, superoxide dismutase (SOD), catalase (CAT), and thiol were decreased in sensitized animals compared to controls (p < 0.01 to p < 0.001). Treatment with all concentrations of extract significantly improved total WBC, TP, NO2, NO3, interstitial fibrosis, and emphysema compared to the S group (p < 0.05 to p < 0.001). Two higher concentrations of the extract significantly decreased neutrophil and monocyte count, malondialdehyde, bleeding and epithelial damage but increased lymphocyte, CAT, and thiol compared to the S group (p < 0.05 to p < 0.001). Dexamethasone treatment also substantially improved most measured parameters (p < 0.05 to p < 0.001), but it did not change eosinophil percentage. It was proposed that A. cepa extract could affect lung inflammation and oxidative stress in sensitized rats.

The effects of vitamin C on respiratory, allergic and immunological diseases: an experimental and clinical-based review.

Vitamin C is used in modern medicine supplements for treatment of various disorders associated with oxidative stress, inflammation and immune dysregulation. In this review article, experimental and clinical results regarding the effects of vitamin C on respiratory immunologic, and allergic diseases are reviewed. Various databases and appropriate keywords are used to search the effect of vitamin C on respiratory diseases until the end of May 2022. Books, theses and articles were included. These studies assessed the effects of vitamin C on respiratory disorders including asthma, chronic obstructive pulmonary disease (COPD), lung infection and lung cancer. Vitamin C showed relaxant effect on tracheal smooth muscle via various mechanisms. The preventive effects of vitamin C were mediated by antioxidant, immunomodulatory and anti-inflammatory mechanisms in the experimental animal models of different respiratory diseases. Some clinical studies also indicated the effect of vitamin C on lung cancer and lung infections. Therefore, vitamin C could be used a preventive and/or relieving therapy in respiratory diseases.

The effects of Artemisia absinthium L. on scopolamine-induced learning and memory impairment and brain tissue oxidative damage in adult rats.

Objective: The present study examined the effects of Artemisia absinthium L. on scopolamine-induced memory dysfunction and brain tissue oxidative damage in rats. Materials and Methods: Fifty rats were used in five groups: Control: received dimethyl sulfoxide (DMSO)/saline, Scopolamine: scopolamine (2 mg/kg) was administered along with DMSO/saline, and Scopolamine-Ext 50, Scopolamine-Ext 100, and Scopolamine-Ext 200 groups: A. absinthium hydroalcoholic extract 50, 100 and 200 mg/kg were administered before scopolamine. The Morris water maze (MWM) and passive avoidance (PA) tasks were used for assessment of behavioral parameters. Malondialdehyde (MDA), nitric oxide (NO) metabolites, total thiol, catalase (CAT), and superoxide dismutase (SOD) were measured in the cortex and hippocampus. Results: A. absinthium decreased the delay time and distance traveled to reach the platform in the MWM test (p<0.05-p<0.001). Besides, the extract increased the delay time to pass in the dark and the light time while decreasing the number of entrances and the dark time in the PA task (p<0.05-p<0.001). In biochemical assessments, A. absinthium attenuated NO metabolites (p<0.001) and MDA (p<0.05- p<0.001) while enhanced total thiol (p<0.001), CAT and SOD (both p<0.05-p<0.001). Conclusion: This study revealed that A. absinthium improved memory and learning impairment and brain tissue oxidative damage in scopolamine-treated rats.

Protective effects of cinnamon on acetylcholinesterase activity and memory dysfunction in diabetic rats.

OBJECTIVES: Regarding neurocognitive and immunomodulatory properties of cinnamon (Cinn) we aimed to investigate whether cinnamon regulates acetylcholinesterase (AChE) activity, and oxidative abnormalities with concomitant memory dysfunction in streptozotocin (STZ)-induced diabetes. METHODS: Forty-seven male adult rats were divided into seven groups (n=8 animals): Control group: in these non-diabetic rats only saline 0.9% NaCl was gavaged, Diabetic (Dia) group: diabetic rats in them saline 0.9% NaCl was gavaged for six weeks. Dia-Cinn 100, Dia-Cinn 200, and Dia-Cinn 400, Dia-Met groups: in these diabetic rats the extract (100, 200, 400 mg/kg respectively) or metformin (300 mg/kg) was gavaged for six weeks. Passive avoidance performance, AChE enzyme activity, and oxidative indicators were examined among the groups. RESULTS: Vs. the control group, blood glucose level and stay time in the dark were remarkably increased in Dia group whereas the latency time was decreased. Meanwhile, antioxidant levels (superoxide dismutase, catalase, and thiols) noticeably decreased in the Dia group compared to the Control group. On the other hand, Cinn extract espicailly at the highest dose recovered the changes similar to those found in the metformin-treated group. CONCLUSIONS: These findings proposed that the cinnamon hydro-ethanolic extract promotes memory recovery in diabetic conditions through the atteuation of the AChE activity and oxidative injury.

Acetyl-11-Keto-ß-Boswellic Acid and Incensole Acetate Attenuate Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting Inflammation and Oxidative Stress.

Boswellia serrata has been used in traditional medicine to treat various inflammatory diseases. Acetyl-11-keto-ß-boswellic acid (AKBA) and incensole acetate (IA) are two active ingredients of B. serrata that possess anti-inflammatory and antioxidant activities. The present study aimed to investigate the protective effects of AKBA and IA against lipopolysaccharide (LPS)- induced acute kidney injury (AKI) in rats. Wistar rats were intraperitoneally pretreated with AKBA or IA for 2 weeks. After 30 min, an LPS injection was applied to induce AKI. Blood samples and kidney tissues were collected and used for biochemical assays. AKBA and IA not only significantly decreased interleukin-6 as a marker of renal inflammation but also attenuated the oxidative stress markers in kidney tissues. AKBA and IA also remarkably decreased serum creatinine and blood urea nitrogen. These results suggest that AKBA and IA have protective effects against AKI in rats through regulating inflammation and oxidative stress.

Carvacrol attenuated neuroinflammation, oxidative stress and depression and anxiety like behaviors in lipopolysaccharide-challenged rats.

Objective: The beneficial effect of carvacrol on neuroinflammation, oxidative damage of brain tissue, and depressive- and anxiety-like behaviors after lipopolysaccharide (LPS) administration were evaluated in rats. Materials and Methods: Vehicle (1% Tween 80), 1 mg/kg of LPS, and carvacrol (25, 50, or 100 mg/kg administered prior to LPS) were injected and behavioral and biochemical tests were done. Results: The results of forced swim test revealed that carvacrol attenuated immobility time and increased activity and climbing times (p<0.05 to p<0.001). The results of elevated plus maze also revealed that treatment by carvacrol prolonged the open arms time and entries and decreased the time and entries in the closed arms (p<0.05 to p<0.01). Carvacrol enhanced crossing, time, and traveled distance in the central segment of the open field and increased total crossing and distance while attenuating the peripheral zone time (p<0.05 to p<0.001). All doses of carvacrol attenuated TNF- α (tumor necrosis factor α) and NO (nitric oxide) in the brain (p<0.01 to p<0.001). The 50 and the 100 mg/kg doses of carvacrol decreased malondialdehyde (p<0.001 for both), and the 100 mg/kg dose of carvacrol increased the content of the thiol (p<0.001). Conclusion: In conclusion, carvacrol improved the behavioral consequences of LPS challenge and attenuated neuroinflammation and brain tissue oxidative stress in rats.

Effect of hydro-alcoholic extract of Cinnamomum zeylanicum on nitric oxide metabolites in brain tissues following seizures induced by pentylenetetrazole in mice.

Objective: The effects of Cinnamomum zeylanicum on oxidative stress imposed by pentylenetetrazole (PTZ) was examined in mice brain tissues. Materials and Methods: Animals were divided into five groups as follows: 1- control group which received saline; 2- PTZ group (100 mg/kg, ip); and groups 3 to 5 which received (100, 200, and 400 mg/kg) of C. zeylanicum for seven days prior to PTZ injection. The latencies of the first minimal clonic seizure (MCS) and the first generalized tonic-clonic seizure (GTCS) and levels of oxidant and antioxidant biomarkers were measured. Results: Treatment with the two higher doses of the extract significantly increased the MCS and GTCS latencies (p<0.05 to p<0.001). Malondialdehyde (MDA) and nitric oxide (NO) levels were increased, but superoxide dismutase (SOD), catalase (CAT), and thiol were decreased in both cortical and hippocampal tissues of the PTZ group compared to the controls (p<0.001). Pretreatment with the two higher doses of C. zeylanicum significantly led to a significant correction in NO, MDA, SOD and CAT levels in the hippocampus and cortex compared to the PTZ group (p<0.05 to p<0.001). Conclusion: Antioxidant and anticonvulsant effects of C. zeylanicum in PTZ-injected animals may suggest its potential therapeutic effect on nervous diseases such as seizures.

The effects of curcumin in learning and memory impairment associated with hypothyroidism in juvenile rats: the role of nitric oxide, oxidative stress, and brain-derived neurotrophic factor.

The effect of curcumin (Cur) on cognitive impairment and the possible role of brain tissue oxidative stress, nitric oxide (NO) levels, and brain-derived neurotrophic factor (BDNF) were investigated in juvenile hypothyroid rats. The juvenile rats (21 days old) were allocated into the following groups: (1) control; (2) hypothyroid (0.05% propylthiouracil (PTU) in drinking water); (3-5) hypothyroid-Cur 50, 100, and 150, which in these groups 50, 100, or 150 mg/kg, Cur was orally administered by gavage during 6 weeks. In the hypothyroid rats, the time elapsed and the traveled distance to locate the hidden platform in the learning trials of Morris water maze (MWM) increased, and on the probe day, the amount of time spent in the target quadrant and the distance traveled in there was decreased. Hypothyroidism also decreased the latency and increased the time spent in the darkroom of the passive avoidance (PA) test. Compared with the hypothyroid group, Cur enhanced the performance of the rats in both MWM and PA tests. In addition, Cur reduced malondialdehyde concentration and NO metabolites; however, it increased thiol content as well as the activity of catalase (CAT) and superoxide dismutase enzymes in both the cortex and hippocampus. Cur also increased hippocampal synthesis of BDNF in hypothyroid rats. The beneficial effects of Cur cognitive function in juvenile hypothyroid rats might be attributed to its protective effect against oxidative stress and potentiation of BDNF production.

Nanoselenium improved learning, memory, and brain-derived neurotrophic factor and attenuated nitric oxide, and oxidative stress in the brain of juvenile hypothyroid rats.

BACKGROUND: Nanoselenium (Nan S) is a form of selenium element that acts with high absorption and low toxicity. However, few studies have examined the effects of Nan S on cognitive impairment. On the other hand, hypothyroidism is a common disease that causes cognitive disorders. Therefore, this study aimed to investigate the effect of Nan S on memory impairment in rats due to propylthiouracil (PTU) - induced hypothyroidism. The roles of brain-derived neurotrophic factor (BDNF), nitric oxide (NO), and oxidative stress were also challenged. MATERIALS AND METHODS: The animals were randomly divided into 4 groups: (1) Control group (normal saline), (2) hypothyroid (Hypo) group: where 0.05% PTU was added to drinking water, (3) and (4) Hypo-Nan S 50, Hypo-Nan S 100 in which 50 or 100 µg/ kg of Nan S were injected respectively. After 6 weeks, spatial and avoidance memory was measured by Morris water maze (MWM) and passive avoidance (PA) tests. The animals then underwent deep anesthesia and the serum samples and the hippocampus and cortex were collected to be used for thyroxin and biochemical measurements including malondialdehyde (MDA), NO, thiol, superoxide dismutase (SOD), catalase (CAT), and BDNF. RESULTS: The rats showed an increase in the escape latency and traveled path in MWM in the Hypo group compare with the Control group and these parameters were decreased in both Hypo-Nan S 50 and Hypo-Nan S 100 groups compared to the Hypo group. The rats of both Hypo-Nan S 50 and Hypo-Nan S 100 groups spent longer time and traveled longer distances in the target area during the probe trial of MWM than the Hypo group. In addition, the latency to enter the dark box in the PA test was lower in the Hypo group than in the Control group, which was significantly improved after Nan S treatment. Furthermore, the hippocampal and cortical lipid peroxide marker (MDA) levels and NO metabolites of the Hypo group were significantly increased and the antioxidant markers (total thiol, SOD, and CAT) were significantly inhibited compared to the Control group. Compared with the Hypo group, Nan S administration could significantly decrease the oxidant factors and increase the activities antioxidant system and concentration of BDNF. CONCLUSION: It is concluded that Nan S might be able to enhance endogenous antioxidant proteins due to its antioxidant activity, thereby improving BDNF and spatial and avoidance memory in the hypothyroidism-induced memory impairment model however, more studies are still necessary to elucidate the exact mechanism(s).

Therapeutic effect of lycopene in lipopolysaccharide nephrotoxicity through alleviation of mitochondrial dysfunction, inflammation, and oxidative stress.

BACKGROUND: Sepsis-associated acute kidney injury (AKI) accompanies a higher mortality in intensive care patients. High-dose lipopolysaccharides (LPS) as an endotoxin is usually used to model AKI in rodents. Lycopene is a fat-soluble carotenoid with proved protective effects in different condition. Rationale and purpose of the study. This research work was designed to assess the effect of lycopene in LPS murine AKI. METHODS AND RESULTS: LPS was injected (intraperitoneally) at 10 mg/kg to induce AKI and lycopene was given (orally) at 5 or 20 mg/kg. Pretreatment of LPS group with lycopene (20 mg/kg) lowered serum BUN, creatinine, and cystatin C and alleviated renal indices of oxidative stress consisting of malondialdehyde and reactive oxygen species and elevated level of catalase activity, superoxide dismutase activity, and glutathione peroxidase activity. In addition, lycopene (20 mg/kg) attenuated renal neutrophil infiltration and reduced renal inflammation, improved mitochondrial membrane potential, and increased gene expression for PGC1-α as a key regulator of mitochondrial biogenesis. In addition, lycopene appropriately reduced level and gene expression of inflammation-related transcription factors including NF-kB and TLR4 and improved level and gene expression of Nrf2 as an important transcription factor related to antioxidant system. Besides, lycopene prevented histopathological changes following LPS in periodic acid-Schiff staining. CONCLUSIONS: Collectively, this study revealed that lycopene has favorable effects by means of amelioration of mitochondrial dysfunction, oxidative stress, and inflammation and accordingly could protect against LPS-induced AKI.

Neuroprotective and memory enhancing effects of Zataria multiflora in lipopolysaccharide-treated rats.

The study was aimed to evaluate the effects of hydro-ethanol extract Zataria multiflora on the brain tissue oxidative damage, and hippocampal interleukin-6 (IL-6) as well as learning and memory capacity in lipopolysaccharide (LPS) - challenged rats. The rats were randomized into five groups as follow: Control group: Rats were treated with saline, LPS group: Rats were treated with LPS 1.00 mg kg-1, ZM50, ZM100 and ZM200 groups in which the rats were treated with Z. multiflora extract (50.00, 100 or 200 mg kg-1 per day, respectively). The treatments including extract or vehicle were administered intraperitoneally and given three days before the behavioral tests and were continued within a6-day behavioral experiment. Injection of LPS was daily done before the behavioral tests. Finally, the brains were collected for biochemical evaluations. Although LPS administration prolonged the latency in Morris water maze and shortened the latency to enter the dark chamber in passive avoidance test, ZM extract restored these changes to approach control group values. Also, LPS increased IL-6, malondialdehyde (MDA) and nitric oxide (NO) metabolites levels and lowered thiol, superoxide dismutase (SOD) and catalase (CAT) levels in the brain, however, Z. multiflora extract reduced IL-6, MDA and NO metabolites concentrations, but increased thiol content, SOD, and CAT levels. The results of this study showed that Z. multiflora ameliorated learning and memory dysfunction in LPS - challenged rats by alleviating of inflammatory responses and brain tissue oxidative damage.

Cardiovascular protective effect of nano selenium in hypothyroid rats: protection against oxidative stress and cardiac fibrosis.

BACKGROUND: Nano selenium (Nano Sel) has many therapeutic properties including antioxidant, anticancer, and anti-inflammatory actions. OBJECTIVE: Impacts of Nano Sel administration against cardiac fibrosis and heart and aorta tissue oxidative damage observed in hypothyroid rats were explored. METHODS: The animals were randomly grouped and treated as: 1) Control; 2) Propylthiouracil (PTU) in which PTU was added to the drinking water (0.05%) to induce hypothyroidism; 3-5) PTU-Nano Sel 50, PTU-Nano Sel 100, and PTU-Nano Sel 150 groups, which received daily PTU plus 50,100 or 150 µg/kg of Nano Sel for 6 weeks intraperitoneally. The heart and aorta tissues were removed under deep anesthesia and then biochemical parameters including malondialdehyde (MDA), total thiol groups, catalase (CAT), and superoxide dismutase (SOD), as well as cardiac fibrosis were assessed. RESULTS: Hypothyroidism induced by PTU was remarkably associated with myocardial hypertrophy and perivascular fibrosis in Masson's trichrome staining. Moreover, hypothyroidism increased MDA level, while it subtracted total thiol group content and activity of SOD and CAT. Treatment with Nano Sel recovered hypothyroidism-induced cardiac fibrosis in the histological assessment. Nano Sel also promoted CAT and SOD activity and thiol content, whereas alleviated MDA levels in the heart and aorta tissues. CONCLUSION: Results propose that administration of Nano Sel exerts a protective role in the cardio vascular system via preventing cardiac fibrosis and inhibiting oxidative stress.