Adverse Effects In Rats Research Articles

Naringin treatment improved main clozapine-induced adverse effects in rats; emphasis on weight gain, metabolic abnormalities, and agranulocytosis.

Schizophrenia is one of the major neuropsychiatric disorders affecting people worldwide. Unfortunately, currently available antipsychotic medications possess several side effects. Among them, clozapine is one of the atypical antipsychotics prescribed in schizophrenia wing to its blocking effect on dopamine (D2) and serotonin (5-HT1c ) receptors. However, it has been recently reserved for resistant schizophrenia due to its several side effects. The current research aimed at investigating potential naringin add-on benefit to cease the main side effects of clozapine in ketamine-induced psychosis in rats. In this study, schizophrenia was induced in rats via ketamine administration that could promote neuropathological patterns of schizophrenia. Afterwards, clozapine and naringin were administered to rats in order to improve such effects induced by ketamine. Clozapine administration promoted weight gain, hyperglycemia, dyslipidemia, and agranulocytosis. However, naringin was able to reduce such adverse effects when added to clozapine treatment. Naringin increased total leukocyte count preventing agranulocytosis either when administered alone or in combination with clozapine. In addition, via its metabolic activities, naringin treatment lowered serum total cholesterol and triglycerides levels. Moreover, naringin prevented weight gain when administered. Finally, naringin reduced serum glucose level preventing hyperglycemia associated with clozapine treatment. Collectively, these findings may suggest that naringin possesses a potential add-on benefit to clozapine in treatment of schizophrenia.

Safety evaluation of whey derived beta-lactoglobulin, Lacprodan® BLG

The safety of Lacprodan® BLG, a whey-based protein, was evaluated with respect to genotoxicity and sub-chronic toxicity according to regulatory requirements. Lacprodan® BLG did not show any mutagenic potential in a bacterial reverse mutation assay or any clastogenic or aneugenic potential in an in vitro micronucleus assay performed in human lymphocytes. In a sub-chronic toxicity study, groups of 10 male and 10 female Wistar rats received the test item orally by gavage for 90 days at dose levels of 100, 300 and 1000 mg/kg bw/day. A control group, also including 10 male and 10 female rats, received sterile water, as vehicle. No treatment-related clinical observations or toxicological effects on body or organ weights, food consumption, ophthalmic effects, hematology, clinical chemistry, fertility, urinalysis, or pathology were identified. Therefore, the no-observed-adverse-effect level (NOAEL) for Lacprodan® BLG in the 90-day toxicity study was established as 1000 mg/kg bw/day, corresponding to the highest dose level administered.

Sub-acute Toxicity Potentials of Albizia chevalieri Extracts on the Histology of the Liver, Kidney and Pancreas using Animal Model

Medicinal plants are used in the treatment of many kinds of ailments in traditional medicine. The aim of this study was to investigate the sub-acute toxicity as well as the histological effect of Albizia chevalieri on liver, kidney, pancrease. The sub-acute toxicity study was conducted for 28 days to examine the toxicity of the extracts and the histology of the rat’s liver, kidney and pancreas. For this study, fresh set of healthy adult of rats of both sexes were used and grouped in to 4 groups of 5 rats each for methanolic extracts and they were labeled accordingly, group 1 received oral dose of 2000 mg/kg body weight, group 2 received 2500 mg/kg body weight, group 3 received 3000 mg/kg body weight and group 4 received 5000 mg/kg body weight per day, respectively, for 28 days using oral gavages’. Clinical observation was carried out for 28 days and their weight were measured weekly for four weeks. On the 28th day the final weight of the rats were measured and then they were anesthetized under diethyl ether the rats were sacrificed and the tissues were preserved in formal saline for histological examinations. The sub-acute toxicity study of the rats showed no significant change on behavior. The methanol extracts of Albizia chevalieri does not produce adverse effects in rats after the sub-acute treatment. Chronic and sub-chronic toxicity evaluations need to be done before marketing Albizia chevalieri.

Ameliorative role of curcumin on copper oxide nanoparticles-mediated renal toxicity in rats: An investigation of molecular mechanisms.

The increasing role of copper oxide nanoparticles (CuO NPs) in many industries and their broad range of applications increase its potential toxic effects. Curcumin possesses a wide range of health benefits. This study aimed to evaluate the role of curcumin in attenuating CuO NPs toxicity in rat kidney. Thirty six animals were divided into five groups; control groups (I, II), curcumin group orally received curcumin 200 mg/kg bw, CuO NPs group orally gavaged 250 mg/kg bw CuO NPs and combined group orally gavaged curcumin and CuO NPs. Treatment was given for 3 months. Administration of CuO NPs revealed elevation in serum creatinine and blood urea nitrogen levels, elevated kidney and urine levels of kidney injury molecule-1, decreased catalase, superoxide dismutase activities, total sulfhydryl, reduced glutathione content, increased serum reactive oxygen species, tissue total oxidant status, lipid hydroperoxides, protein carbonyl, malondialdehyde, nitric oxide levels, increased interleukin-1β, tumor necrosis factor-α, nuclear factor (NF-κB), and decreased heme oxygenase-1 (HO-1) and γ-glutamylcysteine synthetase (γ-GCS) genes expression. Moreover, histopathological alteration in kidney structure was detected. Immunohistochemical-stained sections by caspase-3 reaction revealed apoptosis. Pretreatment with curcumin improved most of the adverse effects in rats treated with CuO NPs regarding oxidative stress and inflammatory indices in kidney, and kept histopathological- and immunohistochemical-stained sections near to normal. This study shows that curcumin administration attenuates the toxicity in the kidney of CuO NPs-treated rats through its antioxidant, anti-inflammatory, and antiapoptotic effects.

In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In Vitro.

Recently, the pentadecapeptide BPC 157-induced counteraction of bupivacaine cardiotoxicity has been reported. Medication includes (i) lidocaine-induced local anesthesia via intraplantar application and axillary and spinal (L4-L5) intrathecal block, (ii) lidocaine-induced arrhythmias, (iii) convulsions, and (iv) lidocaine-induced HEK293 cell depolarisation. BPC 157 applications (intraplantar, intraperitoneal, and intragastric) were given (i) immediately after lidocaine, (ii) 10 min after, or (iii) 5 min before. The BPC 157/NO-system relationship was verified with NO-agents, the NOS-blocker L-NAME and the NOS-substrate L-arginine, given alone and/or together, in axillary and spinal intrathecal blocks. BPC 157 applied immediately after lidocaine or 5 min before the application of lidocaine considerably ameliorated plantar presentation. BPC 157 medication considerably counteracted lidocaine-induced limb function failure; L-NAME was counteracted; L-arginine exhibited counteraction when given immediately after lidocaine, but prolongation was seen when given later. Given together, prophylactically or therapeutically, L-NAME and L-arginine (L-NAME + L-arginine) counteracted the other's response. BPC 157 maintained its original response when given together with L-NAME or L-arginine. When BPC 157 was given together with L-NAME and L-arginine, its original response reappeared. BPC 157 antagonised the lidocaine-induced bradycardia and eliminated tonic-clonic convulsions. Also, BPC 157 counteracted the lidocaine-induced depolarisation of HEK293 cells. Thus, BPC 157 has antidote activity in its own right against lidocaine and local anesthetics.

Update on long-term toxicity of agricultural GMOs tolerant to roundup

Agricultural genetically modified organisms (GMOs) are plants obtained by gene transfer or more recently by gene-editing. Their major common phenotypic trait for which 99% have been modified is that these are designed to be grown with pesticides, which may bioaccumulate in the plants and/or the consumer, and/or express insecticides in their cells. Examples of both types are Roundup-tolerant soy and corn and Bt insecticidal plants. Recently, Steinberg et al. concluded that there were no adverse effects in rats from consumption of a GM corn tolerant to Roundup, called NK603, and that no other long-term studies are justified. This contradicts several of our in vivo studies on the short- and long-term toxicological effects of either the same GMO, other GMOs, or the pesticide Roundup itself. Our results were attributed in particular to the long-term in vivo effects of Roundup residues, which also present toxic and endocrine-disrupting effects in vitro. These effects were clearly linked to the formulants of the pesticide, such as petroleum residues and heavy metals, and not to glyphosate alone. In fact, the treated rats in Steinberg et al.’s experiment showed many adverse effects, some of which, including increased mortality in males fed GM corn + Roundup, were statistically significant. Other adverse effects affected both treated and control groups. The latter trend may be due to contamination of the feed of the control animals by many carcinogenic pollutants, including pesticides, but also by Roundup residues and Roundup-tolerant GMOs. For instance, glyphosate contained in Roundup was found to be 300–1400 times more elevated in their control feed than in our treated group. In conclusion, Steinberg et al.’s study is invalidated by the contaminated feed, biased interpretations, and major undeclared conflicts of interest.

Prevention of excessive exercise-induced adverse effects in rats with Bacillus subtilis BSB3.

AimsTo characterize efficacy of the Bacillus subtilis BSB3 (BSB3) strain in the prevention of excessive exercise‐induced side effects and in maintaining stability of the gut microbiota.Methods and ResultsRats were pretreated by oral gavage with B. subtilis BSB3 (BSB3) or with phosphate‐buffered saline (PBS) twice a day for 2 days, and were either exposed forced treadmill running or remained sedentary. Histological analysis of intestine, immunofluorescence staining of tight junction (TJ) proteins, serum lipopolysaccharide and intestinal fatty acid‐binding protein assay, culture‐based analysis and pyrosequencing for the gut microbiota were performed for each rat. Forced running resulted in a substantial decrease in intestinal villi height and total mucosa thickness, the depletion of Paneth cells, an inhibition of TJ proteins expression. Short‐term treatment of rats with BSB3 before running prevented these adverse effects. Culture‐based analysis of the gut microbiota revealed significant elevation of pathogenic microorganisms only in treadmill‐exercised rats pretreated with PBS. High‐throughput 16S rRNA gene sequencing also revealed an increase in pathobionts in this group. Preventive treatment of animals with BSB3 resulted in predominance of beneficial bacteria.ConclusionsBSB3 prevents excessive exercise‐associated complications by beneficial modulation of the gut microbiota.Significance and Impact of the StudyOur study shows a new application of beneficial bacteria for prevention the adverse effects of excessive exercise.

Nutritional treatment with an immune-modulating enteral formula alleviates 5-fluorouracil-induced adverse effects in rats.

Cancer chemotherapy is frequently accompanied by adverse effects, such as diarrhoea and leukopenia, which lead to malnutrition and a decrease in the patients’ quality of life. We previously demonstrated that an immune-modulating formula (IMF)—an enteral formula enriched with immunonutrients, whey-hydrolysed peptides, and fermented milk—had anti-inflammatory effects and protective effects on intestinal disorders in some experimental models. Here, we investigated whether nutritional treatment with the IMF could prevent 5-fluorouracil (5-FU)-induced adverse effects in rats. Rats were randomised into CTR and IMF groups, which received a control formula or the IMD supplemented formula ad libitum. Two weeks after starting the formula, rats were intraperitoneally injected with 5-FU (300 mg/kg) on day 0. The treatment with 5-FU decreased their body weights, food intake, and leukocyte counts, and worsened the diarrhoea score. However, the body weights, food intake, and leukocyte counts were significantly higher in the IMF rats than in the CTR rats on day 1. The IMF also delayed the incidence of diarrhoea and significantly preserved the villus heights in the jejunum on day 2. In conclusion, nutritional treatment with the IMF alleviated the adverse effects induced by 5-FU injection in rats.

Evaluation of antiviral effect and toxicity of total flavonoids extracted from Robinia pseudoacacia cv. idaho

In this study, we aimed to evaluate the antiviral effect of total flavonoids extracted from Robinia pseudoacacia cv. idaho (RPTF) in vivo and its toxicity on rats with oral gavage. RPTF was prepared by percolation with 70% ethanol for 24 h and its antiviral effect on different kinds of viruses was evaluated in vitro by MTT staining. The long-term toxicity of RPTF on rats was evaluated through the detection of general behavior, body weight, food intake and related organ tissue sections of experimental animals. We found that RPTF produced significantly inhibitory effects on HSV-1 and EV-71 viruses with the therapeutic index TI values 113.8 and 46.2, respectively. Moreover, toxicity evaluation in vivo showed no significantly adverse effects in rats, indicating that RPTF was safe in use. In conclusion, we demonstrated that RPTF, natural compounds in the Chinese traditional medicine, could act as promising and effective antiviral therapeutics with relative safety in use.

Acute and Subacute Toxicity of Methanol Extract of Syzygium guineense Leaves on the Histology of the Liver and Kidney and Biochemical Compositions of Blood in Rats.

Plant medicine is the oldest form of health care known to mankind. Syzygium guineense is one of the many species of Ethiopian medicinal plants which has a long history of use as remedies for various ailments such as dysentery, diarrhea, and hypertension. In many countries, herbal medicines and related products are introduced into the market without safety or toxicological evaluation. The aim of this study was to investigate the histopathological effect of 80% methanol extract of S. guineense on liver and kidney and blood parameters of rats. For acute toxicity study, rats were randomly divided into three groups (n=4). The control group received distilled water, while the experimental groups received a single dose of 2000 mg/kg and 5000 mg/kg 80% methanolic extract of S. guineense leaves per oral. For subacute toxicity study, the rats were randomly divided into three groups (n=6). The control group received distilled water, while the experimental groups received 500 mg/kg and 1500 mg/kg 80% methanol extract of S. guineense leaves orally for 28 days. At the end of the experiment, blood samples were collected for hematology and clinical chemistry evaluations. Gross pathology and histopathology of liver and kidneys were assessed. In the acute toxicity study, rats treated with 2000 mg/kg and 5000 mg/kg showed no toxicological signs observed on behavior, gross pathology, and body weight of rats. In the subacute toxicity study rats have showed no significant changes on behavior, gross pathology, body weight, and hematological and biochemical parameters, whereas both experimental groups had a lower blood glucose level compared with the control group (p < 0.05). There were no significant differences in the gross and histopathology of the liver and kidneys of experimental animals in extract exposed groups and their counterpart control. The 80% methanol extract of S. guineense does not produce adverse effects in rats after acute and subacute treatment. Before marketing a S. guineense leaf based remedy, subchronic and chronic toxicity evaluations need to be done.

Ameliorative role of a combination of chitosan, calcium, vitamins A and E against high fat diets-induced adverse effects in rats

BackgroundChitosan is a promising natural source for controlling obesity. Obese people tend to use supplementary nutrients to compensate for their deficiencies in their diets. The present study aimed to investigate the combined effect of chitosan, calcium, and vitamins A and E supplements against the adverse effects of high-fat diet consumption in rats.MethodsTwenty-five male albino rats were assigned into five equal groups. Control rats were fed standard basal diet (SBD). Another group was fed high-fat diet (HFD) without supplements. The other three groups were fed HFD containing 0, 400, and 800 mg of chitosan per kilogram diet, in presence of calcium and vitamins A and E supplements, daily for 10 weeks.ResultsAs compared to controls, rats fed HFD without supplements showed significant elevations in body weight gain, feed consumption, relative weights of the heart and liver, serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterols, very low-lipoprotein triglycerides, urea, creatinine, and malondialdehyde, as well as serum activities of alanine and aspartate aminotransferases, alkaline phosphatase, and creatine kinase. Moreover, significant declines in the relative kidney weight, serum levels of high-density lipoprotein cholesterols, total proteins, albumin, globulin, calcium, vitamins A and E, erythrocyte glutathione content, and superoxide dismutase activity were recorded. Histopathological alterations were observed in rats fed HFD with or without supplements. On contrary, rats fed HFD containing chitosan and supplements showed remarkable improvement in all the studied parameters towards control values, in dose-dependent manner.ConclusionChitosan, calcium, and vitamins A and E attenuated the adverse effects caused by HFD intake in rats.

Efficacy of brain-targeted rapamycin for treatment of epilepsy in rats

To investigate the efficacy of brain-targeted rapamycin (T-Rap) in treatment of epilepsy in rats. Rapamycin nanoparticles targeting brain were prepared. The epilepsy model was induced by injection of pilocarpine in rats. The rats with pilocarpine-induced epilepsy were treated with rapamycin (Rap group) or brain-targeted rapamycin (T-Rap group). Seizure activity was observed by electroencephalography; the effect on mTOR signaling pathway was detected by Western blot; neuronal death and moss fiber sprouting were analyzed by Fluoro-Jade B (FJB) and Timm's staining, respectively. Electroencephalography showed that both preparation of rapamycin significantly reduced the frequency of spontaneous seizures in rats, and the effect of T-Rap was stronger than that of conventional rapamycin (P<0.05). Western blot showed that the phosphorylation levels of S6K and S6 in T-Rap group were lower than those in Rap group (all P<0.05), indicating that T-Rap had a stronger inhibitory effect on mTOR signaling pathway. FJB staining showed that T-Rap significantly decreased neuronal death, but there was no significant difference as compared with Rap group. Timm's staining showed that both preparations of rapamycin significantly reduced the germination of mossy fibers, while the effect of T-Rap was more pronounced than Rap group (P<0.05). The inhibition of body weight gain of T-Rap group was less than that of Rap group (P<0.05). T-Rap has a better therapeutic effect on epilepsy than conventional rapamycin with a less adverse effects in rats.

Subchronic oral toxicity study of Habb-e-Suranjan in albino Wistar rats.

Abstract Background Habb-e-Suranjan (HS) is a Unani pharmacopoeial formulation used for treatment of rheumatoid arthritis. The present study was carried to evaluate the toxic potential of HS in albino Wistar rats. Methods The subchronic was carried out at the dose levels of 2440 mg/kg of body weight in both sexes. The rats were observed carefully for any behavioral change for next 24 hours (hr) after the administration of the drug and daily twice thereafter till the completion of experimentation. Water/feed consumption and body weight were recorded on weekly basis. The rats were sacrificed on 91st day after overnight fasting. Blood was collected for hematological and biochemical analysis. The rats were dissected and organs were observed for any morphological changes. Organ samples were collected for histological studies. Results There were no incidences of mortality/morbidity found in any of the treated rats. HS caused no significant difference in the body weights as well as relative organs weights of treated groups when compared with the control groups. There were no significant changes found in any biochemical, hematological and histopathological parameters that could indicate any signs of toxicity. Conclusions The study suggests that HS is safe and did not induce any adverse effect in rats.

Can ursolic acid be beneficial against diabetes in rats?

Abstract Objective Diabetes mellitus, a heteregenous metabolic and chronic disease, is a growing health problem especially in developing countries. It is claimed that diabetes associated with increased formation of free radicals and decrease in antioxidant potential and also alterations in lipid profile and enzyme levels. Ursolic acid is commonly used in traditional Chinese medicine due to its beneficial effects. The aim of this study was to investigate the effects of ursolic acid on streptozotocin-induced diabetes in Wistar albino rats. Methods DNA damage was evaluated in the blood and liver cells of rats by alkaline comet assay. The activities of antioxidant enzymes, oxidative stress parameters, biochemical parameters, hepatic enzyme levels and lipid profile parameters were also evaluated. Results The results of this study demonstrate that diabetes caused genotoxic damage, changes in hepatic enzyme and lipid profile, biochemical and antioxidant enzyme activities and oxidative stress parameters in rats. Ursolic acid was found to be protective against diabetes induced effects in blood and liver samples of rats. Conclusions According to our results, it seems that ursolic acid may be beneficial against diabetes and its adverse effects in rats.

Genotoxicity and 28-day oral toxicity studies of a functional food mixture containing maltodextrin, white kidney bean extract, mulberry leaf extract, and niacin-bound chromium complex

Steady-fiber granule (SFG) is a functional food mixture that is composed of four major ingredients, resistant maltodextrin, white kidney bean (Phaseolus vulgaris) extract, mulberry leaf (Morus alba L.) extract, and niacin-bound chromium complex. This study focused on determining the safety of SFG. Genotoxicity and 28-day oral toxicity were evaluated. SFG did not induce mutagenicity in the bacterial reverse mutation assay using five Salmonella typhimurium strains (TA98, TA100, TA102, TA1535, and TA1537) in the presence or absence of metabolic activation (S9 system). SFG also did not induce clastogenic effects in Chinese hamster ovary cells with or without S9 treatment. Similarly, SFG did not induce genotoxicity in a micronucleus test conducted with mice. A dose-dependent 28-day oral toxicity assessment of SFG for rats revealed no significant effects on mortality, body weight, selected organ weights, and behavior. Evaluations of hematology, clinical biochemistry, and histopathology showed no adverse effects in rats treated with SFG. These results suggest that SFG has no significant mutagenic or toxic properties, and the no observed adverse effect level of SFG was defined as at least 5000 mg/kg/day orally for 28 days for male and female rats.

Interactions between Mu and Kappa Opioid Receptor Agonists: Antinociceptive and Adverse Effects in Rats

Prescription opioids (mu opioid receptor agonists) are commonly used to treat moderate to severe pain despite their well‐documented adverse effects (e.g., constipation, abuse). Kappa opioid receptor agonists also have antinociceptive effects and adverse effects, including dysphoria and diuresis that preclude their use in the clinic. Kappa opioid receptor agonists are not likely to be abused, and they might be useful for treating pain in a drug mixture. A mu/kappa opioid mixture might reduce the dose of each drug needed to produce therapeutic (antinociceptive) effects and avoid the adverse effects that occur with larger doses of each drug alone. Additive antinociceptive effects have been reported for the mu/kappa opioid mixture sufentanil:U50488H. The current experiment compared antinociceptive, hypothermic, and rate‐decreasing effects of the kappa opioid receptor agonist spiradoline in combination with the mu opioid receptor agonists morphine or etorphine to test the hypothesis that a mu/kappa opioid mixture selectively enhances antinociceptive effects. All drugs were administered i.p. using a cumulative dosing procedure with 30‐min inter‐injection intervals. Dose‐effect functions were determined in 7 male Sprague Dawley rats for spiradoline (3.2 – 56.0 mg/kg), morphine (1.78 – 32.0 mg/kg), and etorphine (0.001 – 0.1 mg/kg) for latency to remove the tail from warm (40, 50, and 55°C) water and for rectal body temperature. In a separate group of 7 rats, dose‐effect functions were determined for spiradoline and morphine in decreasing responding for food. Given alone, spiradoline and morphine increased tail withdrawal latency from 50°C water to 20 s (maximum); etorphine increased tail withdrawal latency to 15 s. Spiradoline decreased body temperature by approximately 3°C, whereas morphine, but not etorphine, increased body temperature by approximately 1.5°C. Spiradoline alone and morphine alone decreased responding for food to &lt;20% of baseline rates. ED50 values were used to determine the doses for mixtures in ratios of 3:1, 1:1, and 1:3. Mixtures of spiradoline:morphine (3:1 and 1:1) and spiradoline:etorphine (1:1) produced additive antinociceptive effects, and spiradoline:morphine (1:3) produced greater than additive antinociceptive effects (ED50 potency ratio of 1.9). Neither morphine nor etorphine altered the hypothermic effects of spiradoline. Morphine and etorphine enhanced a potentially useful effect (antinociception) as well as an adverse effect (hypothermia) of spiradoline. It remains to be determined whether mu/kappa mixtures also enhance other adverse effects (e.g., constipation, dysphoric effects) and whether enhancement depends on the particular drugs in the mixture. Mu/kappa opioid mixtures may have greater therapeutic potential than mu opioids alone for treating moderate to severe pain, but only if adverse effects of each drug are not enhanced.Support or Funding InformationThis work was supported by the National Institute on Drug Abuse grants K05DA017918 and T32DA031115, the Welch Foundation Grant AQ‐0039, and the ASPET Summer Undergraduate Research Fellowship program.

A Review on the toxicology and dietetic role of bacterial cellulose.

Bacterial cellulose (BC) is a biopolymer synthesized by certain acetic acid bacteria strains. The safety of BC regarding its potential use in food applications is here reviewed. The acute, sub-acute and subchronic oral toxicity assays showed that consumption of BC had no adverse effects in rats. Several studies demonstrated that BC is not genotoxic, did not induce chromosomal aberrations in CHO cells under both non-activating and metabolic activating conditions, is inactive in the in vitro Rat Primary Hepatocyte Unscheduled DNA Synthesis Assay, had no reproductive toxicity in mice and exerted no embryotoxicity and teratogenicity effects in rats.Several studies on the BC in biomedical applications further reinforces its safety: a primary eye and dermal irritation studies in the rabbit showed that BC was non-irritating. The inflammatory reaction to subcutaneously implanted BC has been evaluated in animal models and for different periods of time, demonstrating that BC is biocompatible and does not trigger a harsh inflammatory reaction.Altogether, and considering its longstanding history of human consumption in Asian countries, as well as its utilization in biomedical devices, it may be concluded that BC is safe for applications in food technology.

Therapeutic potential of quercetin against acrylamide induced toxicity in rats

Acrylamide (AA) is found in foods containing carbohydrates and proteins, where it is formed during the heating process. It is classified as neurotoxic and probably carcinogenic to humans. The present investigation was aimed to determine the lethal Dose (LD50) of AA and to evaluate the protective effects of quercetin (QE) against AA induced adverse effects in rats. For the determination of LD50, AA was administered orally at four different doses (46.4mg/kg, 100mg/kg, 215mg/kg and 464mg/kg) to experimental animals for seven days. After 7days LD50 of AA was determined using graphical method of Miller and Tainter. Then AA was administered at 1/3rd dose of LD50 (38.27mgkg−1 body weight; p.o. for 10 days) followed by the therapy of QE (5, 10, 20 and 40mg kg−1 orally), for 3 consecutive days for the determination of protective effect of QE against AA. The estimated LD50 of AA was 114.81mg/kg with 95% confidence interval. Exposure to AA 1/3rd dose of LD50 for 10days induced neurotoxicity which was confirmed by decreased acetylcholinesterase (AChE) activity. AA substantially increased lipid peroxidation (LPO), decreased the level of reduced glutathione (GSH) and antioxidant enzymes (SOD and CAT) in liver, kidney and brain. It also increased the activities of serum transaminases, urea, uric acid, creatinine, lipid profile, bilirubin in serum. Treatment with QE restored tissue and serological indices concomitantly towards normal levels. These results revealed that QE is able to significantly alleviate the toxicity induced by AA in rats.

Protective effect of acanthospermumhispidumethyl acetate extract on hyperglycemic and glycoprotein components in stz induced diabetic rats

Over the past decade, herbal medicines have been accepted universally, and they have an impact on both world health and international trade. Diabetes mellitus is a metabolic disorder in the endocrine system. This dreadful disease is found in all parts of the world and is becoming a serious threat to mankind health. There are lots of chemical agents available to control and to treat diabetic patients, but total recovery from diabetes has not been reported up to this date. Alternative to these synthetic agents, plants provide a potential source of hypoglycaemic drugs and are widely used in several traditional systems of medicine to prevent diabetes. This study was designed to evaluate the effect of Acanthospermum hispidum ethyl acetate extract on the levels of glycoproteins in STZ -induced diabetic Rats. Albino rats were divided equally into four groups: Group 1: control, Group 2: diabetic control , Group 3: diabetic rats treated with 300 mg/kg body weight of plant extract and group 4 diabetic rats treated with 450 mg/kg body weight of plant extract. All treatments were administered via an intragastric tube. Diabetes was induced in the rats of Group 2 by an intraperitoneal injection with 50 mg/kg body weight of STZ Oral administration of plant extract at a concentration of 300 mg/kg body weight and 450 mg/kg body weight for three weeks (21 days) days significantly reduced the levels of blood glucose, glycosylated hemoglobin, and increased in plasma insulin, body weight, as well as those of hexose, hexosamine, fucose, and sialic acid in the diabetic rats treated with the plant extract as compared to untreated diabetic rats, with no adverse effects in rats treated only with plant extract. In conclusion, Acanthospermum hispidum plant extract proved to have a beneficial effect on the diabetic rats in this study. In light of these advantageous results, it is advisable to broaden the scale of use of Acanthospermum hispidum extract in a trial to alleviate the adverse effects of diabetes.

1H-Nuclear magnetic resonance-based metabolic profiling of nonsteroidal anti-inflammatory drug-induced adverse effects in rats

Nonsteroidal anti-inflammatory drugs (NSAIDs), which are globally prescribed, exhibit mainly anti-inflammatory and analgesic effects but also can cause adverse effects including gastrointestinal erosions, ulceration, bleeding, and perforation. The purpose of this study was to investigate surrogate biomarkers associated with the gastrointestinal (GI) damage caused by NSAID treatment using pattern recognition analysis of 1H-nuclear magnetic resonance (1H NMR) spectra of rat urine. Urine was collected for 5h after oral administration of the following NSAIDs at low or high doses: acetylsalicylic acid (10 or 200mgkg−1), diclofenac (0.5 or 15mgkg−1), piroxicam (1 or 10mgkg−1), indomethacin (1 or 25mgkg−1), or ibuprofen (10, or 150mgkg−1) as nonselective COX inhibitors and celecoxib (10 or 100mgkg−1) as a COX-2 selective inhibitor. The urine was analyzed using 500MHz 1H NMR for spectral binning and targeted profiling and the level of gastric damage was examined. The nonselective COX inhibitors caused severe gastric damage while no lesions were observed in the celecoxib-treated rats. The 1H NMR urine spectra were divided into spectral bins (0.04ppm) for global profiling, and a total of 44 endogenous metabolites were assigned for targeted profiling. Multivariate data analyses were performed to recognize the spectral pattern of endogenous metabolites related to NSAIDs using partial least square-discrimination analysis (PLS-DA). The 1H NMR spectra clustered differently according to gastric damage score in global profiling. In targeted profiling, the endogenous metabolites of citrate, allantoin, 2-oxoglutarate, acetate, benzoate, glycine, and trimethylamine N-oxide were selected as putative biomarkers for gastric damage caused by NSAIDs. These putative biomarkers might be useful for predicting the risk of adverse effects caused by NSAIDs in the early stage of drug development process.