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Ischemia reperfusion (IR) injury frequently results from processes that involve a transient period of interrupted blood flow. In the lung, isolated IR permits the experimental study of this specific process with continued alveolar ventilation, thereby avoiding the compounding injurious processes of hypoxia and atelectasis. In the clinical context, lung ischemia reperfusion injury (also known as lung IRI or LIRI) is caused by numerous processes, including but not limited to pulmonary embolism, resuscitated hemorrhagic trauma, and lung transplantation. There are currently limited effective treatment options for LIRI. Here, we present a reversible surgical model of lung IR involving first orotracheal intubation followed by unilateral left lung ischemia and reperfusion with preserved alveolar ventilation or gas exchange. Mice undergo a left thoracotomy, through which the left pulmonary artery is exposed, visualized, isolated, and compressed using a reversible slipknot. The surgical incision is then closed during the ischemic period, and the animal is awakened and extubated. With the mouse spontaneously breathing, reperfusion is established by releasing the slipknot around the pulmonary artery. This clinically relevant survival model permits the evaluation of lung IR injury, the resolution phase, downstream effects on lung function, as well as two-hit models involving experimental pneumonia. While technically challenging, this model can be mastered over the course of a few weeks to months with an eventual survival or success rate of 80%-90%.

Introduction: Acute kidney injury (AKI) is a severe complication of rhabdomyolysis (RM), where skeletal muscle injury leads to the release of cell contents into the bloodstream, ultimately obstructing renal tubules. This results in renal dysfunction due to increased oxidative stress, inflammation, and apoptosis. Glycerol (10 mL/kg) injection is one of the most common methods to induce experimental AKI; but 10 mL/kg dosage seems to be harmful to rats because we have observed some side effects. This study was designed to evaluate the effects of isoflurane pretreatment in the glycerol model of acute kidney injury, but at first we tried to find a better dosage of glycerol to induce AKI less harmful. Methods: 28 male Wistar rats were used in our investigation. We first studied to find the most effective dosage of glycerol for AKI induction in three groups (5, 6.25, and 10 mL/kg), and accordingly 6.25 mL/kg was selected. Secondly, we investigated isoflurane (1.5%, 20 minutes) pretreatment effects on glycerol-induced AKI by estimating blood urea nitrogen (BUN), creatinine (Cr), Bax/Bcl-2 proteins ratio (Bcl-2-associated X/B-cell lymphoma 2), malondialdehyde (MDA), superoxide dismutase (SOD), and histological changes in renal tissues. Results: The results showed that isoflurane pretreatment suppressed oxidative stress and apoptosis, and therefore was able to improve renal function. Conclusion: Isoflurane pretreatment might be protective against rhabdomyolysis-induced AKI because of its anti-oxidant and anti-apoptotic activities. [ABSTRACT FROM AUTHOR]

Neurotoxicity is implicated as a severe complication of chronic kidney disease (CKD). Accumulation of urea and other toxic compounds leads to oxidative stress, inflammation and destruction of the blood-brain barrier. Carbon monoxide (CO) and hydrogen sulfide (H2S) have been shown to have anti-inflammatory, anti-apoptotic, and anti-proliferative properties. The aims of the present study were evaluated the protective effects of CO-releasing molecule (CORM3) and H2S donor (NaHS) on oxidative stress and neuronal death induced by CKD in the hippocampus and prefrontal cortex by considering interaction between CO and H2S on CBS expression. CORM3 or NaHS significantly compensated deficits in the antioxidant defense mechanisms, suppressed lipid peroxidation and reduced neuronal death in hippocampus and prefrontal cortex and improvement the markers of renal injury that induced by CKD. In addition, CORM3 or NaHS significantly improved CBS expression which were reduced by CKD. However, improving effects of CORM3 on antioxidant defense mechanisms, lipid peroxidation, neuronal death, renal injury and CBS expression were prevented by amino-oxy acetic acid (AOAA) (CBS inhibitor) and reciprocally improving effects of NaHS on all above indices were prevented by zinc protoporphyrin IX (Znpp) (HO-1 inhibitor). In conclusion, this study demonstrated that formation of CO and H2S were interdependently improved CKD-induced oxidative stress and neuronal death, which is may be through increased expression of CBS. [ABSTRACT FROM AUTHOR]

Introduction: Given some limitations in the efficacy of N-acetyl cysteine (NAC) or remote ischemic preconditioning (RIPC) to prevent contrast-induced nephropathy (CIN), the present study investigated the beneficial effects of NAC alone or in combination with RIPC on CIN prevention. Methods: Rats were randomly assigned into five groups of eight animals each. Group 1 was shamoperated controls. In group 2, an experimental model of diatrizoate-induced CIN was induced. In groups 3 and 4, NAC (150 mg/kg orally, 24 h before the CIN induction) or RIPC (3 cycles of 4 min/4 min of ischemia and reperfusion in the forelimbs 24 h before the CIN induction) was applied, and both strategies were applied in group 5. 48 hours after the intervention, serum was collected to assess creatinine (Cr) and blood urea nitrogen (BUN) levels. Kidney tissue samples were also kept to evaluate the histology and measure malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Results: Considerable increases in serum Cr (0.82±0.04 vs 0.53±0.03 mg/dl) and BUN (49.87±2.85 vs 22.93±1.11 mg/dl) levels in the CIN group showed renal functional damages compared to the sham group. The morphological changes (2 vs 0 score), increased renal MDA levels (8.11±1.27 vs 3.12±0.52 µmol/100 mg tissue), and decreased renal SOD activity (2.29±0.65 vs 27.32±0.98 U/g tissue) in the CIN group represent a remarkable renal injury and oxidative stress compared to the sham group. The individual use of NAC (serum Cr levels: 0.59±0.01 mg/dl; serum BUN levels: 27.24±1.01 mg/dl; morphological changes: 1 score; renal MDA levels: 4.35±0.58 µmol/100 mg tissue; renal SOD activity: 17.24±1.48 U/g tissue) and RIPC (serum Cr levels: 0.60±0.03 mg/ dl; serum BUN levels: 28.78±1.66 mg/dl; morphological changes: 1 score; renal MDA levels: 5.34±0.53 µmol/100 mg tissue; renal SOD activity: 13.11±1.96 U/g tissue) improved all indices above. However, the combination of NAC and RIPC (serum Cr levels: 0.57±0.01 mg/dl; serum BUN levels: 25.32±1.14 mg/dl; morphological changes: 1 score; renal MDA levels: 3.56±0.52 µmol/100 mg tissue; renal SOD activity: 30.54±2.92 U/g tissue) was more effective than other strategies used alone. Conclusion: The combined use of NAC and RIPC may be more useful in preventing CIN than the individual use of possible additive effects through reducing oxidative stress. Introduction: Given some limitations in the efficacy of N-acetyl cysteine (NAC) or remote ischemic preconditioning (RIPC) to prevent contrast-induced nephropathy (CIN), the present study investigated the beneficial effects of NAC alone or in combination with RIPC on CIN prevention. Methods: Rats were randomly assigned into five groups of eight animals each. Group 1 was shamoperated controls. In group 2, an experimental model of diatrizoate-induced CIN was induced. In groups 3 and 4, NAC (150 mg/kg orally, 24 h before the CIN induction) or RIPC (3 cycles of 4 min/4 min of ischemia and reperfusion in the forelimbs 24 h before the CIN induction) was applied, and both strategies were applied in group 5. 48 hours after the intervention, serum was collected to assess creatinine (Cr) and blood urea nitrogen (BUN) levels. Kidney tissue samples were also kept to evaluate the histology and measure malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Results: Considerable increases in serum Cr (0.82±0.04 vs 0.53±0.03 mg/dl) and BUN (49.87±2.85 vs 22.93±1.11 mg/dl) levels in the CIN group showed renal functional damages compared to the sham group. The morphological changes (2 vs 0 score), increased renal MDA levels (8.11±1.27 vs 3.12±0.52 µmol/100 mg tissue), and decreased renal SOD activity (2.29±0.65 vs 27.32±0.98 U/g tissue) in the CIN group represent a remarkable renal injury and oxidative stress compared to the sham group. The individual use of NAC (serum Cr levels: 0.59±0.01 mg/dl; serum BUN levels: 27.24±1.01 mg/dl; morphological changes: 1 score; renal MDA levels: 4.35±0.58 µmol/100 mg tissue; renal SOD activity: 17.24±1.48 U/g tissue) and RIPC (serum Cr levels: 0.60±0.03 mg/ dl; serum BUN levels: 28.78±1.66 mg/dl; morphological changes: 1 score; renal MDA levels: 5.34±0.53 µmol/100 mg tissue; renal SOD activity: 13.11±1.96 U/g tissue) improved all indices above. However, the combination of NAC and RIPC (serum Cr levels: 0.57±0.01 mg/dl; serum BUN levels: 25.32±1.14 mg/dl; morphological changes: 1 score; renal MDA levels: 3.56±0.52 µmol/100 mg tissue; renal SOD activity: 30.54±2.92 U/g tissue) was more effective than other strategies used alone. Conclusion: The combined use of NAC and RIPC may be more useful in preventing CIN than the individual use of possible additive effects through reducing oxidative stress. [ABSTRACT FROM AUTHOR]

Objective(s): Sepsis-associated encephalopathy (SAE) is a common brain dysfunction following sepsis. Due to the beneficial effects of mesenchymal stem cells (MSCs) therapy on anxiety, an extreme and early manifestation of SAE, we hypothesized that MSCs-derived conditioned medium (CM) may be able to attenuate anxiety in cecal ligation and puncture (CLP)-induced sepsis. Materials and Methods: Rats were assigned into 4 groups: sham, CLP, MSC, and CM. All animals, except in the sham group, underwent the CLP procedure to induce sepsis. Two hours after sepsis induction, the rats in MSC and CM groups, received 1×106 MSCs and CM derived from the same number of cells, respectively. 48 hr after the treatments, anxiety-related behaviors were assessed, and brain and right hippocampal tissues were collected. Results: MSCs and CM enhanced the percentages of open arm entries and time spent in the open arms of the elevated plus-maze and the time spent in the light side of the light-dark box. MSCs and CM decreased the Evans blue content and decreased the IL-6 and TNF-α levels in the brain tissue samples. Reductions in the expression of 5-HT2A receptors and phosphorylation of ERK1/2 and an increase in the expression of 5-HT1A receptors in the hippocampal tissue samples were observed in the MSC and CM groups. Conclusion: MSCs and MSCs-derived CM attenuated anxiety-related behaviors to an equal extent by reducing inflammation, modifying 5-HT receptor expression changes, and inhibiting the ERK pathway. Therefore, MSCs-derived CM may be considered a promising therapy for comorbid anxiety in septic patients. [ABSTRACT FROM AUTHOR]

Asthma is one of the most common respiratory diseases in the world. Nevertheless, it is reported that inflammation induced by asthma is not only restricted to the lung and may cause damaging effects on remote organs. Therefore, this study was designed to investigate the beneficial effects of long-term sodium hydrosulfide (NaHS) administration on lung inflammation and oxidative stress markers to protect the kidney during chronic asthma. BALB/c mice were divided into three groups (n = 5–7): control, asthma and NaHS. Except the control group, sensitization and challenge were performed with ovalbumin. The NaHS group intraperitoneally received 14 μmol/kg NaHS 30 min before each challenge. 24 h after the last challenge, samples of bronchoalveolar lavage fluid (BALF), plasma, lung and kidney tissues were collected. NaHS administration significantly decreased total white blood cell count, percentages of eosinophils, neutrophils and macrophages and increased percentage of lymphocytes. Administration of NaHS considerably decreased the levels of BALF interleukin-13, plasma tumor necrosis factor-alpha (TNF-α), lung malondialdehyde (MDA) and lung phosphorylated nuclear factor-kappa B (p-NF-κB) expression and scores of peribronchial inflammatory cell infiltration, goblet cell hyperplasia and subepithelial fibrosis and increased the activity of lung superoxide dismutase (SOD). The MDA levels and expressions of p-ERK1/2 and Bax were decreased and SOD activity and expressions of Bcl-2 and p-Akt were significantly increased in kidney tissues by NaHS administration. Administration of NaHS decreased renal oxidative stress indices and reduced apoptosis by the inhibition of TNF-α/ERK1/2/Bax. Therefore, H2S may have an essential role in renal protection during asthma. [ABSTRACT FROM AUTHOR]

Interpersonal violence (IPV) is a major public health concern with a significant impact on physical and mental health. This study was designed to evaluate age–sex-specific IPV mortality trends and the assault mechanisms (firearm, sharp objects, and other means), at national and provincial levels, in Iran. We used the Iranian Death Registration System (DRS) and the population and housing censuses in this analysis. Spatio-temporal and Gaussian Process Regression methods were used to adjust for inconsistencies at the provincial level and to integrate data from various sources. After assessing their validity, all records were reclassified according to the International Classification of Diseases, 10th Revision (ICD-10). All ICD-10 codes were then mapped to Global Burden of Disease (GBD) 2013 coding. More than 700 individuals died due to IPV in 1990 and more than twice this number in 2015. The IPV mortality age-standardized rate, per 100,000, increased from 1.62 (95% Uncertainty Interval [UI] = [0.96, 2.75]) in 1990 to 1.81 [1.15, 2.89] in 2015. Among females, the age-standardized mortality rate at national level per 100,000 due to IPV was 1.27 [0.66, 2.43] in 1990 and decreased to 1.08 [0.60, 1.96] in 2015. Among males, the age-standardized mortality rate was 1.96 [1.25, 3.09] in 1990 rising to 2.54 [1.70, 3.82] in 2015. Data from provinces revealed that during the period of our study, Hormozgan province had the largest increase of IPV among females, and Fars province had the largest increase of IPV among males. Conversely, the largest decrease was detected in West Azarbaijan and Qom provinces in females and males, respectively. This study showed a wide variation in the incidence and trends of IPV in Iran by age, sex, and location. The study has provided valuable information to reduce the burden of IPV in Iran and a means to monitor future progress through repeated analyses of the trends. [ABSTRACT FROM AUTHOR]

Objective(s): One of the problems caused by infectious diseases is the decrease in sperm count and motility. Tannic acid is known as an anti-oxidant and anti-inflammatory agent. In this study, Cecal Ligation and Puncture (CLP) sepsis model was induced to investigate the effect of tannic acid on oxidative stress and inflammation in testicular and sperm structure and function. Materials and Methods: Twenty-four male Wistar rats (250-300 g) were randomly divided into 3 groups of 8: 1) sham, 2) sepsis, and 3) sepsis + tannic acid (20 mg/kg at 6, 12, and 24 hr after sepsis induction). Thirty hours after induction of sepsis, testicular samples were collected to measure SOD activity and MDA, IL-6, and TNF-a levels. Another part of the testis was fixed in 10% formalin for histological examinations. Results: In the sepsis group, testicular MDA, TNF-a, and IL-6 levels increased and SOD activity decreased compared with the sham group. In addition, the percentage of motile sperm and the survival rate of sperm decreased significantly in the sepsis group. Administration of tannic acid significantly decreased inflammatory markers (TNF-a and IL-6) and MDA levels and increased SOD activity. Furthermore tannic acid significantly improved sperm parameters and increased sperm and animal survival rates. Conclusion: The results of this study showed that the reproductive system may be strongly affected by the conditions created during sepsis. Tannic acid improved reproductive dysfunction in sepsis by reducing oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Onion or Allium cepa (A. cepa) is one of the most important condiment plants grown and consumed all over the world. This plant has various therapeutic effects attributed to its constituents, such as quercetin, thiosulphinates and phenolic acids. In the present article, various pharmacological and therapeutic effects of A. cepa were reviewed. Different online databases using keywords such as onion, A. cepa, therapeutic effects, and pharmacological effects until the end of December 2019 were searched for this purpose. Onion has been suggested to be effective in treating a broad range of disorders, including asthma, inflammatory disorders, dysentery, wounds, scars, keloids and pain. In addition, different studies have demonstrated that onion possesses numerous pharmacological properties, including anti-cancer, anti-diabetic and anti-platelet properties as well as the effect on bone, cardiovascular, gastrointestinal, nervous, respiratory, and urogenital systems effects such as anti-osteoporosis, anti-hypertensive, antispasmodic, antidiarrheal, neuro-protective, anti-asthmatic and diuretic effects. The present review provides detailed the various pharmacological properties of onion and its constituents and possible underlying mechanisms. The results of multiple studies suggested the therapeutic effect of onion on a wide range of disorders. [ABSTRACT FROM AUTHOR]

The main aim of this study was to assay the testicular H2S levels in the varicocele rat model and then to investigate the protective effects of NaHS on morphometric changes, sperm parameters, oxidative stress and apoptosis markers in rat's testis. D,L‐propargylglycine (PAG) was administrated to show the effects of cystathionine γ‐lyase enzyme (CSE) inhibition in the varicocele. Rats were assigned to four groups: (a) Sham, (b) varicocele, (c) varicocele + PAG and (d) varicocele + NaHS. Animals in varicocele + NaHS group received 30 µmol/L NaHS in drinking water for 56 days. In the varicocele + PAG group, animals received PAG 19 mg/kg twice a week. Morphometric assessment, oxidative stress markers, testicular H2S levels, sperm parameters, TUNEL assay and expression of Bax/Bcl2 were evaluated at the end of experiment. Testicular H2S levels were significantly decreased in varicocele group. NaHS significantly improved sperm parameters, morphometric characteristics and oxidative stress compared to varicocele group. Oxidative stress status deteriorated in the PAG group compared to the varicocele group. This study showed that a low testicular H2S level might play a critical role in male infertility. Thus, NaHS administration may be a promising treatment strategy for male infertility in varicocele. In addition, CSE may not be the only important enzyme in testicular H2S production. [ABSTRACT FROM AUTHOR]

Objective(s): Infertility in varicocele may have an adverse outcome on the future life of an infertile male. This study was designed to investigate whether varicocele affects remote organs, including the kidney, liver, and brain. We have also evaluated the protective effects of NaHS administration on the structure and function of these organs. Materials and Methods: Thirty-six rats were randomly assigned to 3 experimental groups: 1) Sham, 2) Varicocele, and 3) Varicocele + sodium hydrosulfide. Varicocele was induced via partial ligation of the left renal veins. Animals in the Varicocele + sodium hydrogen sulfide group received 30 µmol/l NaHS in drinking water for 56 days. On the 57th day of the treatment, blood samples, as well as kidney, liver, and brain tissues, were collected to assess kidney and liver functions, measurement of oxidative stress markers, and histological changes. For evaluation of sperm parameters caudal epididymis was used. The behavioral tests were performed to evaluate the animal's anxiety-related behaviors. Results: Varicocele caused significant decrease in sperm parameters (motility and viability) and superoxide dismutase activity in the kidney, liver, and brain tissue. Anxiety-related parameters decreased in varicocele. Moreover, varicocele resulted in a significant increase in malondialdehyde levels in the kidney, liver and brain tissue, and liver function enzymes. Varicocele did not alter kidney function parameters. The administration of NaHS improves the above parameters. Conclusion: This study showed that notice to remote organs such as the liver and brain beside reproductive organs in varicocele is important. The administration of NaHS improved remote organ injury in varicocele via its anti-oxidant mechanism. [ABSTRACT FROM AUTHOR]

Varicocele is defined as the non-palpable enlargement of the spermatic venous plexus, which has implications on the sperm quality and fertility. The guidelines for managing varicocele in adolescents are not fully determined yet. However, based on the recent reports, during varicocele injuries to testicular tissues may be a result of the formation of reactive oxygen species (ROS) and the subsequent oxidative damage. The testis has a high metabolism rate and cell replication which itself causes excessive production of the ROS and decreases antioxidant capacity. Massive generation of ROS and their interaction with lipids, proteins and nucleic acids has adverse effects on the normal cell function. This review article describes the varicocele, its etiology, pathophysiological mechanisms and current treatment methods. An electronic search has been conducted, during 2018, via PubMed and Medline database English literature. Peer-reviewed articles were targeted and the following key-words were used: varicocele, diagnosis, etiology, cellular and molecular mechanisms. Available full-text articles were read. Related articles were also scrutinized. A hand search was also driven. Taken together, this review article mention three main pathophysiology of varicocele that can be treated by natural antioxidant. In addition, hydrogen sulfide as another factor was discussed because the reduction of this substance contribute to the male infertility which induce by varicocele. [ABSTRACT FROM AUTHOR]

Introduction: Comorbidity of anxiety has been reported to aggravate the control of asthma symptoms. Considering the important role of oxidative stress in the pathophysiology of asthma and anxiety, the present study evaluated whether hydrogen sulfide (H2S) as an antioxidant agent, has anxiolytic effects in ovalbumin (OVA)-induced chronic asthma. Methods: BALB/c mice were randomly divided into 4 groups (n=8): control, asthma, NaHS (sodium hydrosulfide, a donor of H2S) and ascorbic acid (as a positive control). All animals except in the control group were sensitized and challenged with ovalbumin. Mice in the NaHS group, intraperitoneally received 14μmol/kg NaHS 30min before each challenge. In the ascorbic acid group, 130mg/kg ascorbic acid was given by gavage 30min before each challenge. On the day of the last challenge, animal body weight and anxiety-related behaviors were examined. Results: Asthma caused significant decreases in the percentages of open arm entries and spending time in open arms in the elevated plus maze as well as the spending time in the light side in the light-dark transition. Also, induction of asthma resulted in a significant decrease of the animal body weight. Administration of NaHS as well as ascorbic acid, attenuated anxiety-related behaviors and improved the body weight in asthmatic mice. Conclusion: The current study suggested that NaHS improves anxiety-related behaviors in OVA-induced asthma same as ascorbic acid, a strong antioxidant. Therefore, NaHS appears to be effective for managing the comorbidity of anxiety with asthma. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress is known to play a key role in the occurrence of polycystic ovary syndrome (PCOS) as the most common cause of anovulatory infertility. The purpose of the current study was to investigate whether diminished activity of ovarian enzymes responsible for hydrogen sulfide (H2S) production, cystathionine βsynthase (CBS), and cystathionine γ-lyase (CSE) contributes to oxidative stress in PCOS. The study also explored whether administration of sodium hydrosulfide (NaSH), an H2S donor, could ameliorate PCOS symptoms by reducing oxidative stress. Methods: The total eighteen rats were randomly assigned into three groups (n=6): control, PCOS, and PCOS+NaSH. PCOS was induced by intramuscular injection of estradiol valerate to induce PCOS in the PCOS and PCOS+NaSH groups. The PCOS+NaSH group received 30 μmol/L of NaSH in drinking water for 27 days after PCOS induction. Ovarian tissue samples were analyzed for oxidative stress indices including malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Additional analyses measured H2S levels, CBS, and CSE activity. Results: PCOS induction led to a significant decrease in SOD activity, H2S levels, and CBS and CSE activity, accompanied by a significant increase in MDA levels (p<0.0001). Furthermore, PCOS caused severe histological alterations in the ovaries. However, administration of NaSH effectively restored all measured parameters to pre-PCOS induction levels (p<0.0001). Conclusion: This study showed that the decrease in the activity of H2S-producing enzymes and H2S levels may contribute to oxidative stress in PCOS. Therefore, administration of NaSH as a H2S donor can be considered as a potential therapeutic strategy for PCOS patients. [ABSTRACT FROM AUTHOR]