Subacute Doses Research Articles

Effect of Thiamethoxam Insecticide on Productive Performance of Nile tilapia as well as Water Quality of Fish Tanks

Thiamethoxam (TMX) is a highly toxic systemic neonicotinoid pesticide and its entry into water bodies can greatly endanger human health and aquatic ecosystems. Little is known about the effect of thiamethoxam on Nile Tilapia. Particularly so this experiment was scheduled for three weeks to evaluate the toxic effects of thiamethoxam on productive performance of fish as well as water quality. The used insecticide was Actara 25 WG manufactured by Sygenta, Egypt and it was purchased from Egyptian Company for Seeds and Agricultural Chemicals. It composed of 250 g/kg Thiamethoxam. A total of 200 Oreochromis niloticus with an average initial weight of 15 ± 5 g have been obtained from a commercial fish farm in Kafr Elsheikh province, Egypt. Fish were randomly allotted to five replicated treatments and they were kept at a density of 10 fish / aquaria. Four different concentrations of the insecticide were tested with three replicates of fish for each treatment beside a control group where with no insecticide were used. Tested concentrations of studied insecticide was selected according to lethal concentration 50 (LC50) for Thiamethoxam was 500 mg/l. Statistical analysis of the recorded data clarified that the levels of pH, dissolved oxygen levels (DO), oxygen saturation percentage (DO%) and salinity were significantly different between thiamethoxam treated groups and the control group. In addition, there was a significant difference in final weight and weight gain of fish under experiment in all treatments when compared with the control group. In addition, the lowest significance in the final weight and weight gain was observed at the high chronic dose. Finally, there were no significant differences in mortalities between various treatment groups and the control group with exception to high subacute dose that showed the highest significance of all groups and it was clear that mortalities were increased with increasing thiamethoxam dose as no mortalities were observed in the control group. The present trial clearly showed the toxic effects of thiamethoxam on water quality of fish tank as well as performance and mortality rate in Nile tilapia fish that were live for three weeks in polluted water. Moreover, the result of the present study is of great public health importance because of thiamethoxam residue effects on human health.

Neuroprotective effects of silymarin in 3-nitropropionic acid-induced neurotoxicity in male mice: improving behavioral deficits by attenuating oxidative stress and neuroinflammation.

3-Nitropropionic acid (3-NP) is strongly believed to be an irreversible inhibitor of mitochondrial complex II, leading to neural damage. This study aimed to investigate the neuroprotective effects of silymarin against 3-NP-induced neurotoxicity in male mice. Six-week-old mice received subacute doses of 3-NP intraperitoneally for 17days. Mice were given silymarin (70mg/kg/day, P.O.) for 2weeks before 3-NP administration or for 4weeks after 3-NP administration. At the end of the treatment schedule, animals were evaluated for behavioral alterations. Subsequently, neuronal damage in the hippocampus region of the brain tissues, oxidative stress-related parameters (lipid peroxidation, nitric oxide, superoxide dismutase, glutathione, and total antioxidant capacity), and pro-inflammatory cytokine (TNF-α, IL-17, and IL-1β) levels were evaluated. Our results indicated that 3-NP treatment significantly (p < 0.05) tended to reduce motor coordination, memory, and neuronal antioxidant status while increasing pro-inflammatory cytokine levels. However, silymarin in both treatment and pretreatment protocols markedly (p < 0.05) attenuated the behavioral deficits, oxidative stress status, and neuroinflammation. The results of the current study suggest that the neuroprotective effect of silymarin against 3-NP-induced neurotoxicity might be due to the mitigation of oxidative stress status and provide insight into the therapeutic potential of silymarin.

Biodistribution and intestinal inflammatory response following voluntary oral intake of silver nanoparticles by C57BL/6J mice.

Silver nanoparticles (AgNP) are among the most widely commercialized nanomaterials globally, with applications in medicine and the food industry. Consequently, the increased use of AgNP in the food industry has led to an unavoidable rise in human exposure to these nanoparticles. Their widespread use raises concerns about potential hazards to human health, specifically their intestinal pro-inflammatory effects. Thus, the main objective of this study was to evaluate the biological effects of two subacute doses of 5nm polyvinylpyrrolidone (PVP)-AgNP in C57BL/6J mice. One mg/kg body weight or 10mg/kg bw was provided once a day for 14days, using a new technology (HaPILLness) that allows voluntary, stress-free, and accurate oral dosing. It was observed that after oral ingestion, while AgNP is biodistributed throughout the entire organism, most of the ingested dose is excreted in the feces. The passage and accumulation of AgNP throughout the intestine instigated a prominent inflammatory response, marked by significant histological, vascular, and cellular transformations. This response was driven by the activation of the nuclear factor-кB (NF-кB) inflammatory pathway, ultimately leading to the generation of multiple cytokines and chemokines.

Assessment of the acute and subacute toxicity of the aqueous extract of Moroccan Ferula communis fruit in a mouse model

Ferula communis L. is thought to possess a wide range of therapeutic qualities. This plant's safety is critical regarding its potential uses as a medicine. Using the techniques outlined in the OECD recommendations, the present study aimed to assess the acute and subacute toxicity profiles of Ferula communis aqueous extract (FC-Ext) in mice. In the acute study, the FC-Ext was administered to adult male and female Swiss albino mice through oral and intraperitoneal routes at doses of 0–4 g/kg. The general behavioral effects, mortality rates, and latency of mortality were evaluated for a period of 14 days. For the sub-acute dose study, the FC-Ext was administered orally to adult mice at doses of 125, 250, and 500 mg/kg on a daily basis for 28 days. Body weight and selected biochemical and hematological parameters were measured, and histological examinations of the liver, kidney, and spleen were conducted to assess any signs of organ damage at the end of the treatment period. The results of the acute toxicity study demonstrated that the LD50 values for the oral and intraperitoneal administration of FC-Ext were 3.6 g/kg and 2.3 g/kg, respectively. In the subacute toxicity study of FC-Ext, no significant changes in body weight were observed. However, a substantial increase in the weights of the liver, kidney, and spleen was observed in male mice. The administration of FC-Ext to mice at doses higher than 250 mg/kg resulted in a decrease in white blood cells and platelets in both sexes and a reduction in red blood cells and mean corpuscular hemoglobin concentration in males and hemoglobin in females. No changes in biochemical parameters were observed. Microscopic examination of vital organs such as the liver, kidney, and spleen revealed no significant injuries. Based on the current results, the aqueous extract of Ferula communis has low toxicity. These findings provide important information about the toxicity profile of the traditional medicine plant Ferula communis.

A Sub-Acute Dosing Study of Saxitoxin and Tetrodotoxin Mixtures in Mice Suggests That the Current Paralytic Shellfish Toxin Regulatory Limit Is Fit for Purpose.

Paralytic shellfish poisoning is a worldwide problem induced by shellfish contaminated with paralytic shellfish toxins. To protect human health, a regulatory limit for these toxins in shellfish flesh has been adopted by many countries. In a recent study, mice were dosed with saxitoxin and tetrodotoxin mixtures daily for 28 days showing toxicity at low concentrations, which appeared to be at odds with other work. To further investigate this reported toxicity, we dosed groups of mice with saxitoxin and tetrodotoxin mixtures daily for 21 days. In contrast to the previous study, no effects on mouse bodyweight, food consumption, heart rate, blood pressure, grip strength, blood chemistry or hematology were observed. Furthermore, no histological findings were associated with dosing in this trial. The dose rates in this study were 2.6, 3.8 and 4.9 times greater, respectively, than the highest dose of the previous study. As rapid mortality in three out of five mice was observed in the previous study, the deaths are likely to be due to the methodology used rather than the shellfish toxins. To convert animal data to that used in a human risk assessment, a 100-fold safety factor is required. After applying this safety factor, the dose rates used in the current study were 3.5, 5.0 and 6.5 times greater, respectively, than the acute reference dose for each toxin type set by the European Union. Furthermore, it has previously been proposed that tetrodotoxin be included in the paralytic shellfish poisoning suite of toxins. If this were done, the highest dose rate used in this study would be 13 times the acute reference dose. This study suggests that the previous 28-day trial was flawed and that the current paralytic shellfish toxin regulatory limit is fit for purpose. An additional study, feeding mice a diet laced with the test compounds at higher concentrations than those of the current experiment, would be required to comment on whether the current paralytic shellfish toxin regulatory limit should be modified.

Preclinical In vivo Acute Toxicity Testing of Hyrdoethanolic Extracts of Ficus thonningii Blume (Moraceae) on Wistar Rat Models

Ficus thonningii (Blume) is a medicinal plant whose biological activity has been demonstrated in the management of peptic ulcers. Unfortunately, little scientific data exists on its toxicity. This is why we studied the acute and subacute oral toxicity profile of the hydro-ethanolic extract of the bark of F. thonningii and the systemic exposure of the bioactive components of the plant.Acute toxicity was assessed by administering a single dose of 2000 mg/kg to 5-week-old rats and observed for 14 days. The subacute toxicity study was performed in 6-week-old rats. Animals were orally treated with a daily dose of 125 mg/kg, 250 mg/kg, 500 mg/kg extract for 28 days. A satellite group of animals received 500 mg/kg per day for 28 days and after discontinuation of treatment they were observed for 14 days. Hematological and blood biochemical parameters, as well as kidney and liver histology, were recorded at the end of each experiment. For acute treatment, administration of a dose of 2000 mg/kg did not induce any critical behavioral changes or deaths. Following subacute dosing, biochemical analysis revealed a slight elevation of liver parameters in the 500mg/kg hydroethanolic extract, while no significant increase was observed for kidney parameters. This study showed that daily administration of Ficus thonningii (Blume) for 28 days resulted in the potential to reverse impairment of liver function.

Comparative analysis of Acomyscahirinus and Musmusculus responses to genotoxicity, oxidative stress, and inflammation

The Egyptian spiny mouse, Acomyscahirinus, is a recently described model organism for regeneration studies. It has surprising powers of regeneration with relatively fast repairing mechanisms and reduced inflammation form compared to other mammals. Although several studies have documented the exceptional capabilities of Acomys to regenerate different tissues after injury, its response to different cellular and genetic stresses is not yet investigated. Therefore, the current study aimed to investigate Acomys abilities to resist genotoxicity, oxidative stress and inflammation induced by acute and subacute treatments with lead acetate. Responses of Acomys were compared with those of the lab mouse (Musmusculus), which displays signatures of the “typical” mammalian response to various stressors. Cellular and genetic stresses were induced by using acute and subacute doses of Lead acetate (400 mg/kg and 50 mg/kg for 5 days, respectively). The assessment of genotoxicity was carried out by using comet assay, while oxidative stress was evaluated by measuring the biomarkers; MDA, GSH and antioxidant enzymes CAT and SOD. Moreover, inflammation was assessed by analyzing the expression of some inflammatory-regeneration-related genes: CXCL1, IL1-β, and Notch2 and immunohistochemical staining of TNF-α protein in brain tissue, in addition to histopathological examination of brain, liver, and kidneys. The obtained results revealed a unique resistance potency of Acomys to genotoxicity, oxidative stress, and inflammation in certain tissues in comparison to Mus. Altogether, the results revealed an adaptive and protective response to cellular and genetic stresses in Acomys.

The Effects of Diflubenzuron on Acetylcholinesterase (EC 3.1.1.7) Activity and Liver Ultrastructure in Wistar Rats

Diflubenzuron is a commonly used larvicide/biocidal substance. The present study aimed to reveal the effects of diflubenzuron on Acetylcholinesterase (AChE) enzymatic activity and liver histopathology of a mammalian species (rats). The animals fed with various doses of diflubenzuron and the liver tissues of rats were taken on the 10th, 20th, 25th, 45th days and sixth month. AChE activity of liver was measured by spectrophotometer. Tissues were embedded in Araldite 502 (Sigma), took ultrathin sections, and examined under a 100 CX II Transmission Electron Microscope. AChE activity in the chronic dose of diflubenzuron group was like that in the control group. The enzymatic activity in the subacute dose was found to be significantly different from the control group. After subacute dose exposure was terminated, the AChE activity was still lower on the 45th day compared with the control group. Chronic and subacute doses caused adverse effects to liver tissues, such as numerous mitochondria, abnormally structured nuclei in the hepatocytes and many lipid droplets in the sinusoids of the liver ultrastructure. After the subacute dose was terminated, liver damage was still observed on the 20th and 25th days, but the liver tissue was partly regenerated on the 45th day. Cellular damage might recover after 45 days, but AChE activity probably takes more time to reach a normal level.

Assessment of toxicity and genotoxic safety profile of novel fisetin ruthenium-p-cymene complex in mice.

Throughout the last decades flavonoids have been considered as a powerful bioactive molecule. Complexation of these flavonoids with metal ions demonstrated the genesis of unique organometallic complexes which provide improved pharmacological and therapeutic activities. In this research, the fisetin ruthenium-p-cymene complex was synthesized and characterized via different analytical methods like UV-visible spectroscopy, Fourier-transform infrared spectroscopy, mass spectroscopy, and scanning electron microscope. The toxicological profile of the complex was evaluated by acute and sub-acute toxicity. Additionally, the mutagenic and genotoxic activity of the complex was assessed by Ames test, chromosomal aberration test, and micronucleus based assay in Swiss albino mice. The acute oral toxicity study exhibited the LD50 of the complex at 500mg/kg and subsequently, the sub-acute doses were selected. In sub-acute toxicity study, the hematology and serum biochemistry of the 400mg/kg group showed upregulated white blood cells, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, glucose and cholesterol. However, there was no treatment related alteration of hematological and serum biochemical parameters in the 50, 100, and 200mg/kg group. In the histopathological analysis, the 50, 100, and 200mg/kg groups were not associated with any toxicological alterations, whereas the 400mg/kg group showed prominent toxicological incidences. Nevertheless, the treatment with fisetin ruthenium-p-cymene complex did not exhibit any mutagenic and genotoxic effect in Swiss albino mice. Thus, the safe dose of this novel organometallic complex was determined as 50, 100, and 200mg/kg without any toxicological and genotoxic potential.

A toxicological evaluation for safety assessment of ruthenium-based diosmetin complex in rats

The flavonoid-based organometallic complexes have been identified as novel bioactive compounds with enhanced pharmacological and therapeutic activity. In this study, the ruthenium-p-cymene diosmetin complex was synthesized, characterized, and investigated for toxicological profiling through different toxicological and genotoxicological studies which include acute and sub-acute toxicity, chromosomal aberration, and bone marrow micronucleus study. The acute oral toxicity study demonstrated the LD50 dose of the complex at 500 mg/kg body weight which further instigated the sub-acute doses i.e. 50, 100, and 200 mg/kg. The histopathological analysis demonstrated that the 400 mg/kg dose was associated with severe toxicological incidences of the vital organs (liver, kidney, pancreas, testis, and stomach) except the ovary with increased levels of ALP, AST, ALT, and WBC count. However, 50, 100, and 200 mg/kg doses did not show any toxicological alteration and maintained the normal levels of hematological and serum biochemical parameters. The genotoxicological assessment of the complex depicted no such genetic damage or mutagenicity in any complex treated groups. In conclusion, the 50, 100, and 200 mg/kg doses were determined as therapeutic dose of the novel ruthenium-p-cymene diosmetin complex without any genotoxic and mutagenic potential which can be further implemented in the investigation of various pharmacological and therapeutic interventions.

Potential protective effects of chrysin against immunotoxicity induced by diazinon

Acute intoxication with diazinon (DZN) as a pesticide causes mortality and morbidity annually. This study shows the impact of sub-acute toxicity of DZN 20 mg/kg and the protective activities of chrysin (CH) as a flavone under the flavonoids family (12.5, 25 and 50 mg/kg) were assessed on BALB/c mouse immune system. The changes in morphological and functional properties of the immune system on thymus, spleen and liver histopathology, sub-populations of T lymphocytes, cytokines levels, transcription factors, complement function, phagocytosis, specific and total antibody productions were considered. The histopathological effects of DZN on the spleen and thymus were not significant, but the liver was damaged remarkably. In the presence of CH, the toxic effect of DZN is suppressed. DZN significantly decreased the number of whole blood TCD4+, TCD8+ and NK cells and suppressed the phagocytosis, delayed-type hypersensitivity (DTH) responses to sheep red blood cell (SRBC). Furthermore, it suppressed specific anti-SRBC-Ab, total IgG and IgM production, T-bet expression, and IFN-γ production. In contrast, DZN did not significantly affect complement function and the number of NK cells, TCD4+ and TCD8+ splenocytes. However, it potentiated the expression of GATA-3, ROR-γt and FOXP3 gene expression and consequently produced IL-4, IL-10, IL-17 and TGF-β in whole blood. CH not only significantly increased the variables mentioned above at 12.5, 25 and 50 mg/kg but also could overcome the toxic effects of DZN on whole blood lymphocyte sub-populations and specific and total Ab production in 25 and 50 mg/kg concentrations, phagocytosis and DTH responses in 50 mg/kg, and modulation of the transcription factors and cytokine production, mainly in 25 and 50 mg/kg. In conclusion, DZN in sub-acute doses could remarkably deteriorate immune responses. However, CH can overcome the toxic effects of DZN on the immune components and functions of the immune system.

Psychedelic Cognition-The Unreached Frontier of Psychedelic Science.

Psychedelic compounds hold the promise of changing the face of neuroscience and psychiatry as we know it. There have been numerous proposals to use them to treat a range of neuropsychiatric conditions such as depression, anxiety, addiction and PTSD; and trials to date have delivered positive results in favor of the novel therapeutics. Further to the medical use, the wider healthy population is gaining interest in these compounds. We see a surge in personal use of psychedelic drugs for reasons not limited to spiritual enhancement, improved productivity, aiding the management of non-pathological anxiety and depression, and recreational interests. Notably, microdosing—the practice of taking subacute doses of psychedelic compounds—is on the rise. Our knowledge about the effects of psychedelic compounds, however, especially in naturalistic settings, is still fairly limited. In particular, one of the largest gaps concerns the acute effects on cognition caused by psychedelics. Studies carried out to date are riddled with limitations such as having disparate paradigms, small sample sizes, and insufficient breadth of testing on both unhealthy and healthy volunteers. Moreover, the studies are majoritarily limited to laboratory settings and do not assess the effects at multiple dosages within the same paradigm nor at various points throughout the psychedelic experience. This review aims to summarize the studies to date in relation to how psychedelics acutely affect different domains of cognition. In the pursuit of illuminating the current limitations and offering long-term, forward-thinking solutions, this review compares and contrasts findings related to how psychedelics impact memory, attention, reasoning, social cognition, and creativity.

Acute and sub-acute toxicity studies on an antidiabetic polyherbal formulation in mice

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To investigate the acute and sub-acute toxicity of an Indonesian polyherbal formulation in experimental mice.&#x0D; Methods: Young and healthy Swiss albino mice of both sexes (5 – 6 weeks old), weighing 24 – 25 g were used in this study. Acute toxicity test was conducted in the mice using OECD 425 method and AOT425StatPgm software to determine the polyherbal formulation’s lethal dose (LD50) value, while the sub-acute toxicity test was performed for 28 days using OECD 407 method, by measuring hematological and clinical biochemistry parameters, as well as examining the histology of the liver and kidneys. The acute toxicity test consisted of the following dose groups: 175, 550, 1750 and 5000 mg/kg, while sub-acute toxicity test dose groups were 200, 400 and 800 mg/kg. Each group consisted of 5 male and 5 female mice.&#x0D; Results: Based on the results obtained, LD50 value of the polyherbal formula was &gt;5000 mg/kg. Repeated doses for 28 days showed significant differences (p &lt; 0.05) for white blood cells (WBC) and platelet parameters in male mice, and for mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and platelet parameters in female mice. However, the values were within normal limits. With regard to clinical biochemical parameters - aspartate aminotransferase (AST), Alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, and albumin - there were no significant differences (p &gt; 0.05) between the test groups. Furthermore, no changes were observed in their histological features.&#x0D; Conclusion: The evaluated polyherbal formulation can be considered safe for use in mice. However, clinical trials in diabetic patients at the proposed doses are required to ascertain the formulation’s safety profile.&#x0D; &#x0D; &#x0D; &#x0D;

Mitigation of oxidative stress with dihydroactinidiolide, a natural product against scopolamine-induced amnesia in Swiss albino mice

The present work describes the neuroprotective efficacy of DHAc under escalated oxidative stress condition in scopolamine-induced amnesic mice. During the toxicity test of DHAc in mice, the acute dose (LD50) is found to be 3.468 mg/kg bw and the sub-acute dose is 0.68 mg/kg bw. Improved cognitive and learning abilities are observed in Morris water maze and Y-maze test in 10 days DHAc (0.68 mg/kg bw) treated scopolamine-induced male Swiss albino mice. In the molecular level these changes are monitored as reduced oxidative load followed by significantly lower lipid peroxidation and protein carbonylation, increased superoxide dismutase, catalase, acetylcholinesterase, caspase-3 activity and glutathione content followed by higher expression of anti apoptotic protein bcl-2 in mice brain as compared to scopolamine (1 mg/kg bw) treated mice. Meanwhile real time PCR shows higher expression of brain derived neurotrophic factor (BDNF) and synaptophysin in DHAc pretreated scopolamine treated mice brain. HPLC analysis suggested its possible blood brain barrier crossing ability. Overall DHAc reversed behavioral anomalies in the scopolamine treated mice via oxidative stress quenching, enhancing antioxidative enzyme activity, enhancing BDNF and synaptophysin mRNA levels and reducing expression of apoptotic protein Bax.

Histopathological and inflammatory response in multiple organs of rats exposed to crack

ABSTRACT The aim of this study was to investigate histopathological and inflammatory response in liver and kidney of rats after crack exposure. For this purpose, a total of 32 male Wistar rats were distributed into four groups: (G1) and (G2): received 18 mg/kg of body weight (b.w) of crack cocaine, but Group G2 remained 72 h without exposure after the experimental period (5 days). Experimental group 3 (G3): received 36 mg/kg of body weight (b.w) of crack cocaine. Control Group (CTRL): received only the vehicle (DMSO) administered by intraperitoneal (i.p) route for 5 days. The results showed that crack cocaine induced histopathological changes in liver and kidney. Immunohistochemistry data revealed that G2 group showed a higher immunoexpression of Ki-67 in hepatic and renal tissues. Regarding inflammation, the results showed that all groups exposed to crack cocaine decreased the expression of TNF-α, IL-6, and IL-10 in liver and kidney. In summary, our results showed that the subacute doses of crack cocaine used in this study had cytotoxic, and immunosuppressive effects in liver and kidney of rats, especially at 36 mg/kg dose. Since cellular death and inflammation participates in the multi-step process of chemical carcinogenesis, these data offer new insights into potential ways to understand the pathobiological mechanisms induced by crack cocaine in several tissues and organs.

Acute and sub-acute toxicity profile of crude extract and fractions of Gymnema sylvestre

BackgroundGymnema sylvestre is a reputable medicinal plant commonly explore for the management of diabetes and other ailments in traditional medicine. In the present study, we investigated the phytochemical compositions and effect of crude extract, hexane, and ethyl-acetate fractions of Gymnema sylvestre on biochemical and hematological parameters of Wistar rats.MethodsAlbino rats were distributed randomly into a control group and nine treatment groups orally administered crude extract and fractions of Gymnema sylvestre (100, 300, and 600 mg/kg BW) for 21 days. Liver and kidney function indices, as well as hematological parameters, were monitored.ResultsOur results revealed that the crude methanol extract contains flavonoids (8.56 ± 0.50 mg/g), alkaloids (13.84 ± 0.67 mg/g), total phenol (1.98 ± 0.50 mg/g), saponins (23.85 ± 0.35 mg/g) and tannins (16.00 ± 0.34 mg/g). The crude methanol, ethyl acetate and n-hexane fractions of Gymnema sylvestre had LD50 greater than 5000 mg/kg BW in acute oral toxicity test. The extract and fractions at 300 and 600 mg/kg BW cause loss of body weight of the rats, significantly altered (p < 0.05) the levels of biochemical indices including the aspartate transaminases, alanine transaminase, alkaline phosphates, bilirubin, proteins, urea, creatinine, and white blood cells (WBC) counts when compared with the non-treated control. However, the extract and fractions at 100 mg/kg BW did not cause any significant (p > 0.05) alterations to the levels of biochemical and hematological parameters when compared with the non-treated control.ConclusionGymnema sylvestre at sub-acute doses of 300 and 600 mg/kg BW could compromise the functional integrity of the rats’ liver and kidney. The study, therefore, suggested the use of Gymnema sylvestre for oral remedy at a dose of 100 mg/kg or below.

Toxicity studies of sea anemone (Gyrostoma helianthus) crude extract and fractionated proteins on liver and kidney in rats

Aim: To study the poisonous effects of crude extract and fractionated protein of sea anemone Gyrostoma helianthus on histological and biochemical parameters in male rats. Methodology: Live specimens of Gyrostoma helianthus were collected from Jeddah coast, fixed in ethanol, dried and powdered to obtain the crude residue extract. Some of the crude extract were ultra-filtered to produce protein fractions of 1 and 3KDa. The LD50 of crude extract powder was estimated for male rats and momentary repeated subacute dosing (1/4 LD50) for 7 days was carried out to obtain toxicity data. Histological examination of liver and kidney sections were carried out. Serum whole protein, total albumin, ALT and LDH were estimated by standard protocol. Results: The LD50 of crude extract was 20.32 mg kg-1 for male rats. In acute and subsequent sub-acute toxicity, neurological symptoms such as convulsions, paralysis, tremors, and ataxia were observed overdose exposure. At the end of exposure to subacute dose histopathological changes like hemolyzed blood and atrophy of glomerular tuft in kidney and fatty changes, vacuolation, necrosis, and infiltration in liver was noted. Furthermore, vital significant increase in total protein, ALT and LDH and reduced bilirubin in serum of treated groups was observed as compared to the control. Interpretation: The present study emphasizes the toxicological, behavioral, biochemical, and histological bioactivity of crude extract and protein fractions of 1 and 3 KDa of Gyrostoma helianthus sea anemone, which is commonly found in the Red Sea. The tested extracts were found to be active at a concentration 5.08 mg kg-1. The yielded effects may interpret treatment strategies of toxicological and pharmacologic intervention. Key words: Biochemistry, Gyrostoma helianthus, Histopathology, Toxicity

EFFECT OF CLOVE OIL ON THE BIOCHEMICAL PROFILE OF OVOTESTIS AND HEPATOPANCREAS OF Achatina fulica

The giant African snail Achatina fulica is widespread across the subtropical and tropical countries and has picked up the global pest status. Its voracious feeding capacity and protandrous reproduction makes it almost invincible once established. Measures to combat its menace have for long focussed on chemical molluscicides. However the rising environmental sensitivity in the past few decades has attracted the use of natural compounds to target this pest. The current study was aimed to evaluate the impact of clove oil on the biochemical profile of its ovotestis and hepatopancreas. The snails were randomly divided into three groups i.e., control, vehicle treated group (1% Tween 80) and clove oil treated group. Snails in the clove oil treated group were subjected to subacute doses of clove oil (20% and 60% of LD50 value/24 hrs) by topical application. The activity levels of vital enzymes namely acetylcholinesterase, acid phosphatase, alkaline phosphatase, protease and lactic dehydrogenase were pertinently altered in the ovotestis and hepatopancreas of the clove oil treated snails as compared to the control. Contents of important biomolecules like DNA, RNA, protein, and phospholipids were reduced, the level of lipid peroxidation was significantly enhanced with a concomitant decrease in glutathione content in clove oil treated groups vis-a-vis control in both the tissues studied, highlighting the toxic effect of clove oil to the snail. Thus it is suggested that clove oil can be used in controlling the population of this harmful pest.

Buchholzia Coriacea Exhibited Antinecrotic, Antioxidant and Anti-Inflammatory Potentials in the Sub-Acute Dose of Paracetamol Induced Toxicity

This study was designed to investigate the potential ameliorative effect of the ethanolic seed extract of Buchholzia Coriacea in paracetamol-induced toxicities in male wistar rats using N-acetyl cysteine as a standard drug. Thirty-two male wistar rats were used for the study.

Focused ultrasound enhanced intranasal delivery of brain derived neurotrophic factor produces neurorestorative effects in a Parkinson\u2019s disease mouse model

Focused ultrasound-enhanced intranasal (IN + FUS) delivery is a noninvasive approach that utilizes the olfactory pathway to administer pharmacological agents directly to the brain, allowing for a more homogenous distribution in targeted locations compared to IN delivery alone. However, whether such a strategy has therapeutic values, especially in neurodegenerative disorders such as Parkinson’s disease (PD), remains to be established. Herein, we evaluated whether the expression of tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine catalysis, could be enhanced by IN + FUS delivery of brain-derived neurotrophic factor (BDNF) in a toxin-based PD mouse model. Mice were put on the subacute dosing regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), producing bilateral degeneration of the nigrostriatal pathway consistent with early-stage PD. MPTP mice then received BDNF intranasally followed by multiple unilateral FUS-induced blood-brain barrier (BBB) openings in the left basal ganglia for three consecutive weeks. Subsequently, mice were survived for two months and were evaluated morphologically and behaviorally to determine the integrity of their nigrostriatal dopaminergic pathways. Mice receiving IN + FUS had significantly increased TH immunoreactivity in the treated hemisphere compared to the untreated hemisphere while mice receiving only FUS-induced BBB opening or no treatment at all did not show any differences. Additionally, behavioral changes were only observed in the IN + FUS treated mice, indicating improved motor control function in the treated hemisphere. These findings demonstrate the robustness of the method and potential of IN + FUS for the delivery of bioactive factors for treatment of neurodegenerative disorder.