Melittin as a safe compound to BALB/c mice immune system; a tiered approach immunotoxicity screening.

BACKGROUND: Maintenance of immune system integrity is a vital requirement to protect human body against pathogens/cancers. Natural compounds have long been used due to their benefits for the immune system. One of which is bee venom that contains a peptide called melittin having antimicrobial and anticancer effects. Since a limited number of studies regarding the effects of melittin on the immune system have been carried out, we aimed to evaluate the effects of melittin on BALB/c mice immune system parameters. METHODS: Female BALB /c mice were treated intraperitoneally (i.p) with 0.75 and 1.5 mg/kg doses of melittin for 14 days (5 doses per week). The negative control group received i.p normal saline whereas the positive controls received i.p 20 mg/kg cyclophosphamide (CYP). Immunological parameters such as hematological parameters, delayed-type hypersensitivity (DTH), hemagglutination titer (HA), spleen cellularity, splenocytes proliferation, as well as spleen and bone marrow histopathological assessment were evaluated. RESULTS: Our findings showed that melittin has no gross pathological effect on the spleen and bone marrow. It was also demonstrated that melittin has no any significant effect on hematological parameters. Melittin did not cause any significant changes to proliferation response of splenocytes to PHA and LPS, spleen cellularity, DTH response, as well as the production of anti-SRBC antibodies. According to our results, melittin at 0.75 and 1.5 mg/kg doses could not induce significant changes on immune parameters and as a result, melittin was found to be safe for the mice immune system.

The prevalence of HBV, HCV, and HIV among hemodialysis patients in a tertiary care hospital in Mashhad, Iran.

INTRODUCTION: Hepatitis and acquired immunodeficiency are major health concerns in high-risk patients with renal failure undergoing hemodialysis. This might be due to the number of blood transfusions, age, and dialysis duration. We aimed to investigate the prevalence of HBV, HCV, and HIV in hemodialysis patients to determine the effectiveness of preventive measures already in place and the possible correlation between various risk factors and viral infection in the Hemodialysis Center in Mashhad, Iran. METHODOLOGY: Sixty-five patients were included in a retrospective cross-sectional study. The demographic information was collected. Hepatitis-B surface antigens, anti-HCV, and anti-HIV antibodies were screened using ELISA. RESULTS: Out of 65 patients, 34 (52.3%) were male, and 31 (47.7%) were female. Mean duration of dialysis was 30.68 ± 26.39 months, and the mean age was 64.95 ± 14.09 years. We found 9 (13.8%) patients that were HBV positive (HbsAg-positive), and 3 (4.6%) patients were HCV positive. Sex and the number of blood transfusions were found to be risk factors for HBV infection and had statistical significance (p = 0.02 and p = 0.01, respectively). No statistical significance was found between HBV- and HCV- positivity and the mean age of patients (p = 0.84 and p = 0.76, respectively). All patients were HIV-negative. CONCLUSIONS: Prevalence of HBV was high and significant. More preventive measures need to be developed, and further studies should be conducted to examine the effectiveness of these measures. Moreover, evaluating the prevalence rates of HBV, HCV, and HIV in other hospitals and dialysis centers in Mashhad is recommended to minimize viral infections. Initial HBV vaccination for patients that require hemodialysis is crucial.

Cerium Oxide Nanoparticles Ameliorate Oxidative Stress, Inflammation, and Pain Behavior in Neuropathic Rats.

BACKGROUND: Neuropathic pain originating from a dysfunction in the nervous system is often intractable and chronic. Recently, several studies using nanoparticles suggested a new way to control neuropathic pain. This study intended to explore the potential neuroprotective effect of Cerium Oxide Nanoparticles (CNPs) synthesized by pullulan in neuropathic pain in rats. METHODS: On the right common sciatic nerve of male Wistar rats, the chronic constriction injury (CCI) procedure was used to establish a neuropathic pain model. CNPs were injected into the caudal vein of the rat. Behavioral methods were used to detect mechanical allodynia, cold allodynia, and thermal hyperalgesia in rats. Besides, inflammation factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, nitric oxide (NO), and markers of oxidative stress, including Malondialdehyde (MDA) and total thiol, were measured in the spinal cord segment of rats. RESULTS: In rats with CCI, mechanical allodynia, cold allodynia, and thermal hyperalgesia developed, which improved when the rats were administered CNPs. Spinal cord specimens of CCI rats had elevated inflammation and oxidative stress status (↑IL-1ß, ↑TNF-α, ↑NO, ↑MDA) and decreased antioxidative levels (↓total thiol). As a result of CNPs treatment, these changes were reversed in the spinal cord specimens. CONCLUSION: CNPs alleviate neuropathic pain by exhibiting antioxidative and anti-inflammatory activities.

The significance of thymoquinone administration on liver toxicity of diazinon and cholinesterase activity; a recommendation for prophylaxis among individuals at risk.

BACKGROUND: Diazinon (DZN), a widely used chemical herbicide for controlling agricultural pests, is an important organophosphorus pesticide and an environmental pollutant which induces toxic effects on living organisms during long-term exposure. Thymoquinone (TQ) is a phytochemical bioactive compound with antioxidant and anti-inflammatory properties. We aimed to evaluate the protective effects of TQ against DZN-induced hepatotoxicity through alleviating oxidative stress and enhancing cholinesterase (ChE) enzyme activity. METHODS: Rats were randomly divided into six groups (n = 8); a negative control group receiving corn oil; a group only receiving DZN (20 mg/kg/day); a group treated with TQ (10 mg/kg/day), and three treatment groups as TQ + DZN, receiving different doses of TQ (2.5, 5, and 10 mg/kg/day). All experimental animals were orally treated for 28 consecutive days. The levels of superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactic acid dehydrogenase (LDH) were determined. In addition, ChE activity and histopathological changes were evaluated. RESULTS: The results showed that DZN decreased GSH level (p < 0.01) and SOD activity (p < 0.01) in parallel to an increase in MDA level (p < 0.01) and increased the activity of AST, ALT, ALP, and LDH (p < 0.01) in comparison to the negative control group. Our findings demonstrated that TQ administration could diminish hepatotoxicity and reduce oxidative damage in DZN-treated rats, which could be linked to its antioxidant and free radical scavenging properties. It was also observed that TQ 10 mg/kg remarkably increased the activity of acetylcholinesterase, butyrylcholinesterase, and SOD enzymes, elevated GSH, decreased MDA, and reduced pathological alternations of the liver induced by DZN. CONCLUSION: Thymoquinone 10 mg/kg increased the activity of plasma and blood cholinesterases and reduced DZN-induced alternations of the liver. Improvement of butyryl- and acetylcholinesterase activity suggests that maybe TQ supplement could be beneficial as pre-exposure prophylaxis among farm workers spraying pesticides.

Neuroprotective effect of herniarin following transient focal cerebral ischemia in rats.

Ischemic stroke is a devastating central nervous disease. Despite extensive research in to this area, few innovative neuroprotective treatments have been presented. 7-methoxycoumarin, also known as herniarin, is a common natural coumarin in several plant species. This project examined the effects of the herniarin in rats subjected to the middle cerebral artery occlusion (MCAO). Herniarin at doses of 10 and 20 mg/kg was administered through intraperitoneal injection for 7 days before MCAO induction. Rats were subjected to a 30 min MCAO and a subsequent 24 h' reperfusion. 24 h after the termination of MCAO, neurologic outcome, volume of brain infarction, level of interleukin-1ß (IL-1ß) and tumor necrosis factor alpha (TNF-α), as inflammatory markers, and oxidative stress markers including levels of total thiol, malondialdehyde (MDA), and superoxide dismutase (SOD) activity were estimated. Herniarin administration decreased the MCAO-induced infarct volume and neurological deficits. Moreover, pretreatment with herniarin significantly decreased the levels of MDA while simultaneously increasing the level of total thiol and SOD activity in the brain tissues of MCAO rats. Moreover, herniarin pretreatment decreased the levels of IL-1ß and TNF-α in the brain tissues of MCAO rats. These results suggest that herniarin presents beneficial effects against ischemic stroke, partly through the inhibition of oxidative stress and inflammation.

Protective Effect of Capparis spinosa Extract against Focal Cerebral Ischemia-reperfusion Injury in Rats.

BACKGROUND: Ischemic stroke is a serious public health problem. Despite extensive researches focusing on the area, little is known about novel treatments. OBJECTIVE: In this study, we aimed to investigate the effects of Capparis spinosa (C. spinosa) extract in the middle cerebral artery occlusion (MCAO) model of ischemic stroke. METHODS: Wistar rats underwent 30-min MCAO-induced brain ischemia followed by 24 h of reperfusion. C. spinose was administrated orally once a day for 7 days before the induction of MCAO. The neurologic outcome, infarct volume (TTC staining), histological examination, and markers of oxidative stress, including total thiol content, and malondialdehyde (MDA) levels, were measured 24hr. after the termination of MCAO. RESULTS: Pretreatment with C. spinosa reduced neurological deficit score, histopathological alterations, and infarct volume in treated groups compared to the stroke group. Furthermore, pretreatment with C. spinosa extract significantly reduced the level of MDA with concomitant increases in the levels of thiol in the brain tissues compared to the stroke group. CONCLUSION: Our study demonstrates that C. spinosa extract effectively protects MCAO injury through the attenuation or the suppression of the oxidative stress.

Hypnotic Activity of Capparis spinosa Hydro-alcoholic Extract in Mice.

BACKGROUND: Sleep disorders are among the most common psychiatric and medical conditions. Herbal medicine appears to be effective in the treatment of sleep disorders which have been valued by many of publications and patents. OBJECTIVE: The present study aimed at investigating the hypnotic activity of the hydro-alcoholic extract of Capparis spinosa (HAE) in mice. METHODS: Three doses of HAE (30, 60 and 120 mg/kg) and three fractions of it, namely n-hexane fraction (NHF), water fraction (WF), and ethyl acetate fraction (EAF), were given in comparison with diazepam (3 mg/kg body weight i.p.) as a positive control and saline as a negative control. After 30 min, pentobarbital (30 mg/kg body weight i.p.) was administered. In addition, LD50 of HAE was examined and the cytotoxicity of HAE was assessed in l929 cells using the MTT assay. Moreover, for motorcoordination ability, 30 mins after administration of HAE, the rotarod test was performed. RESULTS: The results exhibited that the HAE and all the fractions significantly augmented pentobarbital induced sleeping time, which was comparable to that of induced by diazepam. The LD50 value was 2.4 g/kg. The extract did not induce any cytotoxic effects in L929 fibroblast cells. HAE did not affect the animals' performance on the rotarod test. CONCLUSION: Our finding suggests that the hydro-alcoholic extract of C. spinosa possesses a hypnotic potential that may require further scientific investigations.

Antioxidant and toxicity studies of biosynthesized cerium oxide nanoparticles in rats.

PURPOSE: The purpose of this study was to investigate the acute toxic potential of cerium oxide nanoparticles (CNPs) synthesized by pullulan in adult male Wistar rats. PATIENTS AND METHODS: Thirty male Wistar rats randomly were divided into five experimental groups of six animals each. The animals were received 50, 100, 200, and 400 mg/kg CNPs for 14 consecutive days. At the end of the experiment, the rats were euthanized and histopathological evaluation of the liver and renal tissues, as well ass, the markers of serum oxidative stress including thiobarbituric acid reactive substances, total sulfhydryl content, and antioxidant capacity (using ferric reducing/antioxidant power assay) were assessed. Hematological parameters and the activity of liver function enzymes were also measured. RESULTS: The results of this study showed that CNPs caused no significant changes in the activity of liver enzymes, hepatic and renal histopathology and hematological parameters, while significantly improved serum redox status. CONCLUSION: Acute administration of pullulan-mediated CNPs is safe and possess antioxidant activity.