Acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin in mice after intraperitoneal administration

AimsThe objective of this work was to evaluate the acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP), after their intraperitoneal administration in male and female mice.Main methodsAfter single administration of free CDDP (5,10,and 20 mg/kg) or SpHL-CDDP (7,12,30,45 and 80 mg/kg), the body weight was recorded and the LD₅₀ was calculated. Blood samples were collected for biochemical and hematological analysis. Kidneys, liver, spleen and bone marrow were removed to histopathological examination.Key findingsMice treated with high doses of free CDDP showed a greater loss of body weight and more delayed recovery time than those treated with SpHL-CDDP. The LD₅₀ values for SpHL-CDDP treatment for male and female mice groups were 2.7 and 3.2 fold higher, respectively, than that obtained for free CDDP. The red and white blood cells counts and quantification of hemoglobin and hematocrit presented no change upon administration of SpHL-CDDP treatment. Free CDDP treatment, however, did lead to an appearance of mild anemia and a reduction in total white blood cell counts. As regards nephrotoxicity, it was observed that free CDDP treatment caused pronounced alterations in the blood urea and creatinine levels of mice. In contrast, these parameters were slightly altered only after SpHL-CDDP treatment at a dose of 30 mg/kg. Microscopic analysis of kidneys from mice treated with SpHL-CDDP showed no morphological alteration. Concerning hepatotoxicity, no histopathological alteration was observed after both treatments.SignificanceThese findings reveal that SpHL-CDDP can eliminate CDDP-induced toxicity and is thus a promising candidate for intraperitoneal chemotherapy.     

Steady-State Serum T3 Concentrations for 48 Hours Following the Oral Administration of a Single Dose of 3,5,3'-Triiodothyronine Sulfate (T3S)

ObjectiveSulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A desulfating pathway reverses this process, and thyromimetic effects have been observed following the parenteral administration of 3,5,3′-triiodothyronine (T₃) sulfate (T₃S) in rats. The present study investigated whether T₃S is absorbed after oral administration in humans and if it represents a source of T₃.MethodsTwenty-eight hypothyroid patients (7 men and 21 women; mean age, 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T₃) prior to ¹³¹I remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group), or 160 μg (16 patients/group) of T₃S was administered 3 days before the planned administration of ¹³¹I. Blood samples for serum T₃S and total T₃ (TT₃) concentrations were obtained at various times up to 48 hours after T₃S administration.ResultsAt all T₃S doses, serum T₃S concentrations increased, reaching a peak at 2 to 4 hours and progressively returning to basal levels within 8 to 24 hours. The T₃S maximum concentration (C_max) and area under the 0-to 48-hour concentration-time curve (AUC_0-48h) were directly and significantly related to the administered dose. An increase in serum TT₃ concentration was observed (significant after 1 hour), and the concentration increased further at 2 and 4 hours and then remained steady up to 48 hours after T₃S administration. There was a significant direct correlation between the TT₃ AUC_0-48h and the administered dose of T₃S. No changes in serum free thyroxine (T₄) concentrations during the entire study period were observed, whereas serum thyroid-stimulating hormone levels increased slightly at 48 hours, but this was not related to the dose of T₃S. No adverse events were reported.Conclusion(1) T₃S is absorbed following oral administration in hypothyroid humans; (2) after a single oral dose, T₃S is converted to T₃ in a dose-dependent manner, resulting in steady-state serum T₃ concentrations for 48 hours; (3) T₃S may represent a new agent in combination with T₄ in the therapy of hypothyroidism, if similar conversion of T₃S to T₃ can be demonstrated in euthyroid patients who are already taking T₄. (Endocr Pract. 2014;20:680-689)     

Evaluation of protective efficacy of flaxseed lignan-Secoisolariciresinol diglucoside against mercuric chloride-induced nephrotoxicity in rats

The toxicity of heavy metals such as mercury (Hg) in humans and animals is well documented. The kidney is the primary deposition site of inorganic-Hg and target organ of its toxicity. The present study investigated the protective efficacy of flaxseed lignan-Secoisolariciresinol diglucoside (SDG) on nephrotoxicity induced by mercuric chloride (HgCl₂). Rats were intraperitoneally injected with HgCl₂ (2 mg/kg/day) and renal toxicity was induced. Subcutaneous administration of rats with SDG (5 mg/kg/day) as a pre-treatment caused a significant reversal of HgCl₂ induced increase in blood urea, creatinine, glutathione s-transferase and catalase (CAT). On the other hand, administration of SDG with HgCl₂ restored normal levels of albumin and superoxide dismutase (SOD). Histological examination of kidneys confirmed that pre-treatment of SDG before HgCl₂ administration significantly reduced its pathological effects. Thus, the results of the present investigation suggest that SDG can significantly reduce renal damage, serum and tissue biochemical profiles caused by HgCl₂ induced nephrotoxicity. Hence, SDG may be recommended for clinical trials in the treatment of kidney disorders caused by exposure to Hg.

     

Toxicity profiling of the ethanolic extract of Citrullus lanatus seed in rats: behavioral,biochemical and histopathological aspects

Citrullus lanatus (Cucurbitaceae) is conventionally used for the treatment of urinary tract infection, renal stones, hypertension, diabetes and diarrhoea. Current study evaluates acute and 28 days repeated toxicity ethanolic extract of C. lanatus seed (EECLS) in Wistar rats to measure its safety profile. The single dose (2000 mg/kg BW) of EECLS was administered while in 28 days repeated study 250, 500 and 1000 mg/kg BW were administered orally in rats. Parameters such as biochemical, haematological and histopathological were analysed in subacute toxicity study. During study, no apparent sign of toxicity, behavioural changes and mortality were detected in acutely exposed animals. In 28 days repeated toxicity study, rats did not show significant changes in behaviour, gross pathology, body weight, biochemical and haematological parameters. Abridged serum glucose and cholesterol levels during the study designate their roles in treatment of hyperglycaemic and hyperlipidaemic conditions. No significant difference was observed in histopathology of liver and kidneys of treated rats. The current investigation demonstrated that EECLS is non-toxic below 1000 mg/kg BW and provides protection to some body organs. The data propose that LD₅₀ of EECLS was greater than 2000 mg/kg BW and the no observed adverse effect level (NOAEL) of EECLS was at the dose of 1000 mg/kg in rats. Taken together, our finding suggests that, EECLS is safe and provides some protection to body organs; also, its extract can be used for further preclinical and clinical evaluation for its therapeutic activity.     

Doxorubicin chemotherapy affects intracellular and interstitial nitric oxide concentrations in skeletal muscle

The role of nitric oxide (NO) in doxorubicin (DOX; cancer chemotherapeutic)-induced cardiotoxicity is well established. In skeletal muscle (SM), NO regulation plays a critical role in health, biogenesis, and function. Despite the increasing evidence that indicates the negative impact of DOX on SM function, the effect of DOX on NO production in SM has yet to be examined. The purpose of the current study was to simultaneously examine intracellular and interstitial NO concentrations in the SM following the administration of DOX. A single dose of 1.5 or 4.5 mg/kg was administered intraperitoneally to male Sprague Dawley rats, and interstitial (IS) and intracellular (IC) NO was quantified every 24 up to 192 h post-injection. There was no significant difference in IC NO following the injection of 1.5 mg/kg DOX when compared to the control; however, the administration of 4.5 mg/kg DOX resulted in lower (P?<?0.05) concentrations of NO in the IC. Interestingly, a consistently higher (P?<?0.05) concentration of NO in the IS was established following the administration of 1.5 mg/kg compared to the control while no significant changes in IS NO resulted from the administration of the 4.5 mg/kg dose. The fluctuation of IS and IC NO was not a result of substrate availability as arginine concentrations remained stable throughout the experiment. By utilizing the microdialysis technique, we have simultaneously quantified for the first time the IS and IC concentrations of NO in SM following DOX administration. These data provide important insight in the possible mechanisms leading to DOX-related SM dysfunction.     

<Emphasis Type="Italic">In vivo</Emphasis> studies with a <Emphasis Type="Italic">Candida tropicalis</Emphasis> isolate exhibiting paradoxical growth <Emphasis Type="Italic">in vitro</Emphasis> in the presence of high concentration of caspofungin

We investigated the activity of caspofungin against a Candida tropicalis clinical isolate showing paradoxical growth in vitro. BALB/c mice immunosuppressed by cyclophosphamide were infected intraperitoneally using 10⁷ CFU/mouse. Caspofungin was administered intraperitoneally once daily for 5 days or as a single dose using the following doses: 0.12, 0.25, 1, 2, 3, 5, and 15 mg/kg. The single dose of caspofungin was effective only at 5 and 15 mg/kg concentrations (100% survival). Five-day caspofungin treatment led to 100% survival at doses of 1 mg/kg or higher. Caspofungin treatment significantly decreased the number of viable yeasts in the peritoneal lavage samples as well as in the infected abscesses at doses 1, 3, 5, and 15 mg/kg caspofungin as compared to the untreated control (P<0.001 in all cases), and even to the group treated with 0.12 mg/kg caspofungin (P<0.05 in all cases). At 2 mg/kg caspofungin dose, sterilization of the internal organs was reproducibly incomplete, suggesting that the role of paradoxical growth in the late clinical failure cannot be excluded.     

Efficacy of Cyclooctadepsipeptides and Aminophenylamidines against Larval,Immature and Mature Adult Stages of a Parasitologically Characterized Trichurosis Model in Mice

Background

The genus Trichuris includes parasites of major relevance in veterinary and human medicine. Despite serious economic losses and enormous impact on public health, treatment options against whipworms are very limited. Additionally, there is an obvious lack of appropriately characterized experimental infection models. Therefore, a detailed parasitological characterization of a Trichuris muris isolate was performed in C57BL/10 mice. Subsequently, the in vivo efficacies of the aminophenylamidines amidantel, deacylated amidantel (dAMD) and tribendimidine as well as the cyclooctadepsipeptides emodepside and in particular PF1022A were analyzed. This was performed using various administration routes and treatment schemes targeting histotropic and further developed larval as well as immature and mature adult stages.

Methodology/Principal Findings

Duration of prepatent period, time-dependent localization of larvae during period of prepatency as well as the duration of patency of the infection were determined before drugs were tested in the characterized trichurosis model. Amidantel showed no effect against mature adult T. muris. Tribendimidine showed significantly higher potency than dAMD after oral treatments (ED₅₀ values of 6.5 vs. 15.1 mg/kg). However, the opposite was found for intraperitoneal treatments (ED₅₀ values of 15.3 vs. 8.3 mg/kg). When emodepside and PF1022A were compared, the latter was significantly less effective against mature adults following intraperitoneal (ED₅₀ values of 6.1 vs. 55.7 mg/kg) or subcutaneous (ED₅₀ values of 15.2 vs. 225.7 mg/kg) administration. Only minimal differences were observed following oral administration (ED₅₀ values of 2.7 vs. 5.2 mg/kg). Triple and most single oral doses with moderate to high dosages of PF1022A showed complete efficacy against histotropic second stage larvae (3×100 mg/kg or 1×250 mg/kg), further developed larvae (3×10 mg/kg or 1×100 mg/kg) and immature adults (3×10 mg/kg or 1×100 mg/kg). Histotropic first stage larvae were only eliminated after three doses of PF1022A (3×100 mg/kg) but not after a single dose.

Conclusions/Significance

These results indicate that the cyclooctadepsipeptides are a drug class with promising candidates for further evaluation for the treatment of trichurosis of humans and livestock animals in single dose regimens.     

Use of an antiarrhythmic drug against acute selenium toxicity

ObjectiveSelenium is an essential trace element. But, selenium may have toxic effects in high doses. There are no proven antidotes or curative treatments for acut selenium toxicity. Treatment involves stopping the exposure and providing supportive care for symptoms. Therefore, it is necessary to find more effective substances in the treatment of selenium toxicity. The aim of this study was to increase the survival rate of animals by supporting the heart with amiodarone and to determine the effect of amiodarone on the pathological, hematological and biochemical parameters in acute selenium intoxication.Methods64 Wistar-Albino rats were divided into four groups. Group I was given only distilled water, Group II was given 18 mg/kg dose of amiodarone, Group III was given 18 mg/kg amiodarone and 10 mg/kg sodium selenite and Group IV was given sodium selenite 10 mg/kg (LD₅₀ dose)orally.Results11 of the 16 animals in Group IV died within the first 48 h of drug administration. However, no deaths were observed in the rats in Group III. No hematological changes were observed. Biochemically, CK, CK-MB and LDH levels of Group IV were higher than the other groups on both the 2nd and 10th days. In Groups II and III, this serum level decreased, and vitamin B12 levels increased. In macroscopic inspections of the organs of Groups III and IV, slight paleness was detected. Histopathologically, degenerative changes in tissue were observed, especially in Group IV.ConclusionThis study shows that amiodarone application has a reducing effect on selenium toxicity. This was because amiodarone protected the heart by reducing CK and CK-MB levels and increased vitamin B12 levels, which play a role in the synthesis of S-adenosyl methionine that converts selenium into a nontoxic form.     

Prostacyclin (PGI2) effets on anterior pituitary hormones in the rat in vivo

Intravenous injection of 600 μg PGE₂ or PGI₂ significantly increased serum LH and prolactin levels in estradiol treated ovariectomized rats. There was no effect on serum FSH concentration. PGE₂ and PGI₂ stimulated LH release in a non-dose dependent manner, while prolactin levels were positively correlated with the dose administered following PGI₂ treatment. 6-keto-PGF_1α at a comparable dose had no effect on pituitary hormone levels. Subcutaneous administration of 1 mg/kg or 60 mg/kg PGI₂ for seven days significantly depressed serum LH level both in male and female rats. These doses had no effect on serum FSH or prolactin levels.     

The protective effect of taurine pretreatment on carbon tetrachloride-induced hepatic damage--a light and electron microscopic study

Summary.  The results regarding taurine pretreatment on CCl₄-induced hepatic injury are controversial. To assess the therapeutic efficacy of taurine on rat liver injury, hepatic malondialdehyde, glutathione, and hydroxyproline levels together with morphologic alterations in the liver following CCl₄ administration were investigated. The rats were divided into three groups. Taurine-treated animals received 15 ml/kg/day of a 5% taurine solution by a gastric tube for 5 days before administering CCl₄ (2 ml/kg, intraperitoneally, in a single dose). CCl₄-treated rats received the same amount of saline solution. Control animals received no treatment. The increase of hepatic malondialdehyde formation in the CCl₄-treated group was partially prevented by taurine pretreatment, but taurine had no significant effect on the glutathione and hydroxyproline content in the CCl₄-treated rats. Taurine pretreatment induced a marked beneficial effect regarding the prevention of hepatocellular necrosis and atrophy as demonstrated morphologically. In conclusion, these results suggest that taurine pretreatment might not significantly change the biochemical parameters, but prevents the morphologic damage caused by CCl₄ in the early stages. Received March 17, 2001 Accepted July 18, 2001     

Rosmarinus officinalis essential oil modulates renal toxicity and oxidative stress induced by potassium dichromate in rats

BACKGROUNDChromium hexavalent (CrVI) is known as a toxic contaminant that induced oxidative stress and nephrotoxicity in humans and animals. Rosmarinus officinalis is a perennial herb rich in biologically active constituents that have powerful antioxidant properties. So, the current work evaluated the effectiveness of Rosmarinus officinalis essential oil (REO) against alterations induced by potassium dichromate in the kidney of male rats.METHODSGC-MS analysis, in vitro total phenol contents, and DPPH scavenging activity of REO were estimated. Thirty-five Wistar male rats were categorized into 5 groups. The first group was the control, the second one was orally administered rosemary essential oil (REO; 0.5 mL/kg BW), the third group was injected intraperitoneally with hexavalent chromium (CrVI; 2 mg/kg BW) for 14 days, the fourth group used as the protective group (REO was administrated 30 min before i.p. injection of CrVI) and the fifth group applied as the therapeutic group (rats injected with CrVI 30 min followed by oral administration of REO), respectively.RESULTSTwenty-nine components were detected with high total phenolic contents and high DPPH scavenging activity. Results revealed that CrVI- intoxicated rats showed a valuable increase in oxidative stress profile (TBARS and H₂O₂) and a notable decline in glutathione (GSH), total protein content, and enzymatic antioxidants (SOD, CAT, GPx, and GST). Furthermore, serum kidney functions biomarkers (urea, creatinine, and uric acid) were increased significantly. Also, the administration of CrVI showed histological and immunohistochemical (PCNA-ir) changes in rat kidney tissue. Otherwise, administration of REO pre or post-treatment with CrVI significantly restored most of the biochemical parameters in addition to improvement in kidney tissue architecture. Moreover, individual intake with REO exhibited an amendment in oxidative stress markers.CONCLUSIONConclusively, REO had a potential antioxidant capacity in ameliorating K₂Cr₂O₇-induced nephrotoxicity, especially in the protection group.     

Induction of hepatic drug metabolizing enzymes by DL-methionine in rats

A single intraperitoneal injection of DL-methionine (500 mg/kg body wt.) to adult male Wistar rats was shown to significantly induce all the components of the hepatic microsomal mixed function oxidase system such as NADPH cytochrome C reductase activity, cytochromes P-450 and b₅, as well as activities of drug metabolizing enzymes such as aminopyrine demethylase and uridine 5′ -diphosphate-glucuronosyltransferase. Combined administration of nicotinamide (250 mg/kg body wt.) and DL-methionine (500 mg/kg body wt.) was shown to bring about an additional increase (25-30%) in the activities of these enzymes as compared to their induction on independent administration of the two endobiotics. In rats bearing Yoshida sarcoma (ascites) tumour as well as in normal rats injected with serum from tumour bearing animals, the decreased activities of hepatic mixed function oxidases could be restored to their normal levels by administration of DL-methionine (500 mg/kg body wt.) to these rats. Whereas actinomycin D (1 mg/kg body wt.) had no effect on the increased incorporation of [¹⁴C] labelled leucine into microsomal proteins following administration of nicotinamide, the enhanced incorporation of the label following DL-methionine administration was completely inhibited by the same dose of actinomycin D. Administration of cycloheximide (0·5 mg/kg body wt.) to rats could completely inhibit the increased incorporation of [¹⁴C] leucine into hepatic microsomal proteins following independent administration of nicotinamide and DL-methionine. Similar inhibitory pattern with actinomycin D and cycloheximide was also demonstrated in case of induction of NADPH cytochromeC reductase activity by both these endobiotics.     

The monoacylglycerol lipase inhibitor JZL184 suppresses inflammatory pain in the mouse carrageenan model

AimThe present study tested whether the selective monoacylglycerol lipase (MAGL) inhibitor JZL184 would reduce allodynia and paw edema in the carrageenan test.Main methodsThe anti-edematous and anti-allodynic effects of JZL184 were compared to those of PF-3845, an inhibitor of fatty acid amide hydrolase (FAAH), and diclofenac, a non-selective cyclooxygenase inhibitor. Cannabinoid receptor involvement in the anti-edematous and anti-allodynic effects of JZL184 was evaluated by administration of the respective CB₁ and CB₂ receptor antagonists rimonabant and SR144528 as well as with CB₁(?/?) and CB₂(?/?) mice. JZL184 (1.6, 4, 16, or 40 mg/kg) was administered for six days to assess tolerance.Key findingsJZL184 administered before or after carrageenan significantly attenuated carrageenan-induced paw edema and mechanical allodynia. Complementary genetic and pharmacological approaches revealed that the anti-allodynic effects of JZL184 required both CB₁ and CB₂ receptors, but only CB₂ receptors mediated its anti-edematous actions. Importantly, both the anti-edematous and anti-allodynic effects underwent tolerance following repeated injections of high dose JZL184 (16 or 40 mg/kg), but repeated administration of low dose JZL184 (4 mg/kg) retained efficacy.SignificanceThese results suggest that the MAGL inhibitor JZL184 reduces inflammatory nociception through the activation of both CB₁ and CB₂ receptors, with no evidence of tolerance following repeated administration of low doses.     

In Vivo Efficacy of a Synthetic Coumarin Derivative in a Murine Model of Aspergillosis

Despite advances in therapeutic modalities, aspergillosis remains a leading cause of mortality. This has necessitated the identification of effective and safe antifungal molecules. In the present study, in vivo safety and antifungal efficacy of a coumarin derivative, N, N, N-Triethyl-11-(4-methyl-2-oxo-2H-benzopyran-7-yloxy)-11-oxoundecan-1-aminium bromide (SCD-1), was investigated. The maximum tolerable dose of compound was determined according to OECD 423 guidelines. The compound could be assigned to category IV of the Globally Harmonized System and its LD₅₀ cut-off was found to be 2000 mg/kg body weight. The survival increased in Aspergillus fumigatus-infected mice treated with a dose of 200 mg/kg, orally or 100 mg/kg body weight, intraperitoneally, of SCD-1 in comparison to infected-untreated animals. The SCD-1 treatment resulted in significant reduction in colony counts in vital organs of the animals. Its protective effect was also observed on day 14 as there was marked reduction in fungal colonies. The treatment with SCD-1 also reduced the levels of serum biochemical parameters with respect to infected-untreated animals. It could be concluded that SCD-1 is a quite safe antifungal compound, which conferred dose dependent protection against experimental aspergillosis. Therefore, SCD-1 holds potential for developing new formulations for aspergillosis.     

Ameliorative effect of carnosine and N-acetylcysteine against sodium nitrite induced nephrotoxicity in rats

The widespread use of sodium nitrite (NaNO₂) for various industrial purposes has increased human exposure to alarmingly high levels of nitrate/nitrite. Because NaNO ₂ is a strong oxidizing agent, induction of oxidative stress is one of the mechanisms by which it can exert toxicity in humans and animals. We have investigated the possible protection offered by carnosine (CAR) and N-acetylcysteine (NAC) against NaNO ₂-induced nephrotoxicity in rats. Animals orally received CAR at 100 mg/kg body weight/d for seven days or NAC at 100 mg/kg body weight/d for five days followed by a single oral dose of NaNO ₂ at 60 mg/kg body weight. The rats were killed after 24 hours, and the kidneys were removed and processed for various analyses. NaNO ₂ induced oxidative stress in kidneys, as shown by the decreased activities of antioxidant defense, brush border membrane, and metabolic enzymes. DNA-protein crosslinking and DNA fragmentation were also observed. CAR/NAC pretreatment significantly protected the kidney against these biochemical alterations. Histological studies supported these findings, showing kidney damage in NaNO ₂-treated animals and reduced tissue impairment in the combination groups. The protection offered by CAR and NAC against NaNO ₂-induced damage, and their nontoxic nature, makes them potential therapeutic agents against nitrite-induced nephrotoxicity.     

Effects of a Fusarium toxin-contaminated maize treated with sodium metabisulphite,methylamine and calcium hydroxide in diets for female piglets

Deoxynivalenol (DON) and zearalenone (ZEN) contaminated maize was hydrothermally treated in the presence of sodium metabisulphite (SBS), methylamine and calcium hydroxide (Ca(OH)₂) and included into diets for female piglets to evaluate effects on performance, organ weights, development of hyperestrogenism, serum biochemical parameters, stimulation of peripheral blood mononuclear cells and toxin residues in serum. For this purpose, both uncontaminated maize (CON) and Fusarium toxin-contaminated maize (FUS) were included into diets either untreated (?) or treated (+) according to a 2 by 2-factorial design. One-hundred female weaned piglets were assigned to one of the four treatment groups (n = 25) CON?, CON+, FUS? and FUS+ with DON/ZEN concentrations of 0.43/0.03, 0.04/0.0, 3.67/0.32 and 0.36/0.08 mg per kg diet, respectively. After a feeding period of 27 days, 20 piglets (n = 5) were slaughtered. Performance parameters such as feed intake, live weight gain and feed-to-gain ratio remained unaffected by the treatments. Uterus weights were significantly reduced in group FUS+ compared to FUS? (p = 0.028), while visceral organ weights were not influenced. Vulva width in relation to body weight was highest in group FUS? at the end of the trial, while hydrothermal treatment significantly reduced the parameter (p < 0.01). The highest toxin and toxin metabolite concentrations in serum were detected in group FUS?, whereas ingestion of diet FUS+ reduced the concentrations to the level of the control groups. Serum biochemical and haematological parameters were mainly within the given reference ranges and showed no treatment-related alterations. Stimulation of peripheral blood mononuclear cells was not affected. An effective detoxification of maize by hydrothermal treatment in the presence of SBS, methylamine and Ca(OH)₂ could be demonstrated by means of serum toxin analyses. No undesired side effects of the treated-feed stuff or the chemicals themselves on the health of piglets were detected.     

Absorption,tissue distribution,metabolism and elimination of taurine given orally to rats

Summary. Three biodisposition studies with taurine were performed in male and female adult rats at dosages of 30 and 300 mg/kg. A single oral dose of ¹⁴C-taurine was rapidly absorbed, distributed to tissues and excreted unchanged in urine. Elimination of radioactivity from intracellular pools was slow. Pre-treatment of animals for 14 days with unlabelled taurine did not significantly affect the fate of ¹⁴C-taurine. At the higher dose there was more extensive excretion combined with a lower percentage of the dose in the carcass, indicating the possibility of saturation of the tubular reabsorption mechanism for taurine. Daily administration of unlabelled taurine for 14 days did not result in an increase in total taurine in the brain. The data indicate that exogenous taurine rapidly equilibrates with endogenous body pools and that any excess is rapidly eliminated by the kidneys.     

Studies on the embryotoxicity and mutagenicity of mycotoxins

Embryotoxicity: Aflatoxin B₁(AFB₁), G₁ (AFG₁), and Patulin (PA) were investigated in NMRI mice for embryotoxic and teratogenic activity. These three mycotoxins were injected intraperitoneally or given orally on day 12 and 13 of pregnancy. AFB₁ (15, 45, and 90 mg/kg ip or 45 mg/kg po) produced a moderate retardation in the fetal development and a dose related increase of cleft palates, wavy ribs, and diaphragm changes. The effects after injection of AFG₁ (45 and 90 mg/kg ip) were reduction of fetal weights, increase of diaphragm changes, and malformations of kidneys. PA (1.25, 2.5, and 3.75 mg/kg ip or 3.75 mg/kg po) elevated the rate of cleft palates after 3.75mg/kg. In the dominant lethal assay neither PA (2.5 and 5 mg/kg ip) nor AFB₁) (15 and 45 mg/kg ip) increased the frequency of the dominant lethal mutations. Both mycotoxins showed no mutagenic activity in this test system. The capability of AFB₁, AFG₁, and PA to induce chromosome damages in vivo was tested in the Chinese Hamster by examination of bone marrow cells, each after two oral doses (AFB₁: 12.5 and 25 mg/kg; 25 and 50 mg/kg; PA: 10 and 20 mg/kg). The three mycotoxins induced chromosome aberrations in the following order of activity: PA > AFB₁ > AFG₁.