What is the difference between toxicity and cytotoxicity

Notwithstanding, there were no difference among the groups on clinical signs patterns, such as salivation and diarrhea. Central nervous system depressant action of flavonoid glycosides. Eur J Pharmacol It is well known that gamma aminobutyric acid GABA , the major inhibitory neurotransmitter in the CNS, is vital for the overall balance between neuronal inhibition and excitation through its interaction with specific heteromeric GABA-gated chloride channels receptor.

Many studies have been correlated to the affinities of diverse natural and synthetic flavonoids for the benzodiazepine binding sites located to the GABA receptors to their pharmacological effects in vivo such as anticonvulsant, sedative or anxiolytic effect Viola et al. Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects. Planta Med Pharmacological studies on synthetic flavonoids: comparison with diazepam. Neuropharmacology Flavonoids and the CNS.

Molecules Flavonoids, such as apigenin, quercetin and chrysin, are sedative in rodents Gouteman et al. Other experiments must be undertaken to clarify this mechanism. The hematopoietic system is one the most sensitive target for toxic molecules Olson et al.

Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol J Toxicol, p. In this report, both red and white blood cells profile was analyzed as important toxicological index. Here, we did not observe any haematological toxicity effect and did not interfere or cause any injury to the circulating red and white blood cells or platelets, corroborating the wide safety margin of the EEStb. In addition, EEStb neither modified serum glucose levels nor body temperature data not shown , supporting that EEStb have no toxic effect acutely.

Once that, those organs represent the most sensitive to show toxicity when they are exposed to potential harmful compounds Olson et al. Acute toxicity study and effect of prolonged administration 28 days of crude ethanolic root extract of Ebenaceae on clinical, haematological and biochemical parameters of albino rats.

J Ethnopharmaco l Acute treatment with EEStb at both doses showed a normal liver architecture with cords of hepatocytes CH very well arranged, sinusoid capillaries S and central veins CV without alterations as well as normal kidney architecture with glomerulus G surrounded by the Bowman's capsule BC. EEStb 2. Those changes should be confirmed by histomorfometric analysis. Renal Tubules RT without any inflammatory changes when compared with the control Figure 2. It is well established that serum enzymes alanine ALT and aspartate AST transferase are sensitive biomarkers to evaluate hepatotoxicity.

ALP activity, on the other hand, is related to the functioning of hepatocytes Pan et al. Mouse toxicity of Anabaena flos-aquae from Lake Dianchi, China.

Environ Toxicol In the present study, there were no significant changes in hepatic enzymes, suggesting that the EEStb did not cause any damage to the hepatic functions. Further, no impairment was detected in kidney function marks such as increasing in creatinine and urea levels table IV. Albumin and globulin are the most important plasmatic proteins and they represent a good criterion for assessing synthetic liver capacity Pan et al.

Hepatoprotetive activity of chitosan against isoniazid and fifampicin-induced toxicity in experimental rats. Excretory function of the liver. Int Rev Physiol In this study, EEStb did not change albumin, globulin and urea levels at first and 14 th days of experiment table IV.

Considering that histopathological analysis and microscopy examination did not reveal any insult in liver or kidney histomorphology Figure 2 , our results suggest that the EEStb did not show nephrotoxic and hepatotoxic effects. Substances with LD 50 higher than 1. The results suggest that EEStb is safety to the popular use and it makes the species interesting for future pharmacological investigation.

This extract did not cause cytotoxicity in any concentrations. Further studies on the mechanism of action of EEStb and its effects on cell lines under laboratory conditions are in progress. This study is the first reports in literature that provide preliminary in vitro and in vivo evidences about the Spondias tuberosa safety.

The data show that EEStb did not cause any death or acute toxicity signs, as well as also showed mitogenic effect, suggesting the EEBSt as a promise to future biological investigation. The species is widely used for traditional communities in Brazil Northeast for different purposes; including treatment of several diseases and this study constitute safety information to human and animal use as well as future pharmacological studies to guarantee the safety of this plant species when used as a phytomedicine.

The phytochemical profile associated to absence of toxic effects highlights the EEStb promise to future pharmacological investigations. Abrir menu Brasil. Abrir menu. ABSTRACT Spondias tuberosa Arruda, popularly named as umbu, is native from savanna-like vegetation and widely used for medicinal purposes, however, the toxicological profile is not available yet. Preparation of Extract The ethanolic extract of S. Isolation and characterization of polymorphic microsatellite loci in Spondias radlkoferi Anacardiaceae.

Appl Plant Sci 3: Safety assessment of standardised methanol extract of Cinnamomum burmannii Phytomedicine Chemical composition, antioxidant and antibacterial activities of two Spondias species from Northeastern Brazil. In vitro cytotoxicity assays involving tissue specific cell cultures are considered as valuable predictors of human drug toxicity. However, there are no uniform cytotoxicity test methods and all these existing methods have particular problems.

Measuring cell cytotoxicity also proves to be quite indispensable in the process of developing therapeutic anti-cancer drugs. By determining the cytotoxicity levels of cancer cells, anti-cancer medications can hinder the proliferation of target cells either by messing with their genetic material or by blocking the nutrients that the cells needs to survive. Additionally, understanding the mechanisms involved in cytotoxicity can likewise give researchers a more in-depth knowledge on the biological processes both normal and abnormal governing cell growth, cell proliferation, and death.

Identification of cytotoxic chemicals may be crucial in helping to explain target cells, and organ toxicity and species differences. Understanding the consequences of the induced natural or chemical substances should be helpful in creating proper different models for extrapolation to low doses.

In addition, biomarkers of exposure are gaining importance as tolls in the cytotoxicity research. The detection of the cytotoxic chemicals in humans may be useful in assessing human exposure or cellular injury.

Also, understanding specific mechanisms may be useful in identifying the potential target tissues in vivo because cell types have different capacities to handle different types of chemicals.

Today, we need to understand the cytotoxicity that particular cells, organs, and organism are facing and identifying specific treatment interventions to address their unique needs both at macro- and micro-levels. The scope of this book goes precisely toward this direction. Each chapter offers the ways of intervention to address some of the most pressing cytotoxic chemicals of our time. Cytotoxicity book is a web based resource, encompassing some of the cytotoxicity natural and different chemical substance, such as natural coumarins, colchicine alkaloids, titania nanosheets, asbestos fiber, nanomaterials, nanocrystals, and composites, and curcumin loaded copolymer encapsulated ZnO nanocomposites.

The book is an useful and ideal guide for novice researchers interested in learning research methods to study cytotoxic bioactive compounds. Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3.

Help us write another book on this subject and reach those readers. Login to your personal dashboard for more detailed statistics on your publications. Scr alterations were not sustained but irreversible in both female and male rats in all dosage XF and PXF groups. Some transient increasing of them were found. Whether this increase is related to the death of these rats still need to be investigated.

That indicated that the renal fibrosis risks still existed although no fibrosis was found in the pathological examination of liver and kidney.

Adverse effects of Xanthii Fructus were frequently reported in recent years, although the toxicity of Xanthii Fructus is clearly alerted in the Pharmacopoeia of China edition. Moreover, its basic toxicity data and related mechanism were not well investigated.

In this manuscript, we systemically evaluated the in vitro and in vivo toxicity of Xanthii Fructus, its processed product, and its major chemical constituent. Atractyloside was frequently reported to be a toxic substance of Xanthii Fructus. The toxic mechanisms of atractyloside were also well explained. Atractyloside competitively inhibits the adenine nucleoside carrier in isolated mitochondria and thus blocks oxidative phosphorylation [ 10 ].

Atractyloside inhibits gluconeogenesis and fatty acid oxidation but accelerates anaerobic glycolysis and glycogenolysis. The metabolic alterations in humans and animals include an acute hyperglycaemic phase, due to rapid depletion of skeletal muscle and hepatic glycogen, inhibition of glycogen synthesis, and a subsequent marked hypoglycaemic phase. The rapidly declining plasma glucose resulted in insufficient glucose delivery to the brain to sustain normal functions.

As the severe hypoglycaemia persisted, depression of respiration, hypoxaemia, tissue hypoxia diminished oxygen consumption , acidosis, convulsion, coma, and, in some cases, death followed. However, in this experiment, atractyloside did not show such obviously toxic effects as other published researches. We consulted this to the differences between in vitro and in vivo research results. Limited metabolic enzyme and limited exposure time might restrict the exposure of atractyloside toxicity.

Moreover, toxic effects induced by atractyloside might be mediated by its in vivo metabolite, which could not happen in our in vitro experiment system. In vivo toxicity assays provided more information and basic data for the clinical usage of Xanthii Fructus. Both XF and PXF displayed severe acute toxicity in times of human highest dosage; however, this dosage was too extreme in the clinical usage.

Fortunately, the single dose administration of XF and PXF was safe even at 10 times of allowed human highest daily dosage. No obvious behavioral changes, blood cell analysis results changes, and general organ lesions were observed in this dosage. Chronic toxicity assays focused on the more common dosage with high probability of occurrence in clinical practice.

In order to evaluate their toxicity to kidney, BUN and Scr were tested as the function index of kidney. The BUN test, along with the creatinine test, is primarily used to evaluate kidney function in a wide range of circumstances to help diagnose kidney disease and to monitor people with acute or chronic kidney dysfunction or failure. Increased BUN levels suggest impaired kidney function.

This may be due to acute or chronic kidney disease, damage, or failure. It may also be due to a condition that results in decreased blood flow to the kidneys, such as congestive heart failure, shock, stress, recent heart attack, or severe burns, due to conditions that cause obstruction of urine flow, or due to dehydration.

Synthesis and accumulation of large quantities ECM were foundations of kidney fibrosis. Notable changes in body weight and blood cell and BUN and Scr changes occurred sporadically in middle and high dosage groups after the 9th week.

Although some liver and kidney pathological damage was found in the high dosage groups, no early stage changes of renal fibrosis were found. All the above results indicated that the single use of even 10 times the permitted highest dosage of XF and PXF is safe. Adverse effects or even death casesoccurred after continuous administration of 3 times or 9 times the permitted dosage of XF and PXF for 2 months.

The authors declare that there is no conflict of interests. Supplement Tables provided the data of BUN and Scr values in female and male rats in chronic toxicity assays, respectively. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors.

Read the winning articles. Journal overview. Special Issues. Academic Editor: Swaran J. Received 27 Jul Revised 11 Oct Accepted 11 Oct Published 26 Nov Materials and Methods 2. Figure 1. Photographs of Xanthii Fructus and its processed product.

Figure 2. Structure of atractyloside potassium salt AL. Table 1. Table 2. Table 3. Figure 3. Table 4. Mice grouping, treatments, and responses in acute toxicity testing. Figure 4. Comparison of microscopic morphology in kidney a, b, and c , liver d, e, and f , heart g, h, and i , and lung j, k, and l tissue between control group a and d , high dosage XF group b and e , and high dosage PXF group c and f.

A significant difference compared with XF groups in the same dosage,. Table 5. Their BWs were reduced gradually. Total 9 11 BW: body weight. Table 6. Table 7. Group I: only mild edema was observed. Group II: mild-to-moderate tubular edema, renal interstitial inflammation, tubular exudation, and tubular necrosis were observed. Group III: mild-to-moderate tubular edema, renal interstitial inflammation, tubular exudation, and tubular necrosis were observed.

Group VII: mild-to-moderate tubular edema, renal interstitial inflammation, tubular exudation, and tubular necrosis were observed. Group I: mild hepatocytes edema degeneration was observed. Group II: mild-to-moderate edema degeneration, mild-to-moderate spotty necrosis, focal necrosis, and mild degree inflammation were observed. Group III: Mild-to-moderate edema degeneration, mild-to-moderate spotty necrosis, focal necrosis and mild-to-moderate degree inflammation were observed. Group VII: mild-to-severe edema degeneration, mild-to-moderate spotty necrosis and mild degree inflammation were observed.

Group VII: mild-to-moderate tubular edema, renal interstitial inflammation, tubular exudation, and tubular necrosis were observed b Microscopic morphology in liver. Figure 5. Figure 6. Figure 7. The indicates a significant difference compared with XF groups in the same dosage, , , and. Figure 8. Only Scr values in partly treatment groups with significant alterations were shown in this figure.

Weeks Female Male 4th 8th 12th 4th 8th 12th I