The protective effect of rutin against renal toxicity induced by lead acetate

Flavonoids are known to have powerful antioxidant activity that could play a protective role in oxidative stress-mediated diseases. Rutin (RT) is a flavonol glycoside composed of the flavonol quercetin and disaccharide rutinose. The protective effect of RT against nephrotoxicity induced by lead acetate was evaluated. Male albino rats of Wistar strain were used in this study. Animals were given lead acetate after a week of pretreatment with RT (50?mg/animal/day). Lead acetate exposure resulted in an increase in the uric acid, creatinine (CRN) and blood urea nitrogen (BUN) levels and a decrease in glutathione, superoxide dismutase, catalase and glutathione peroxidase (GPx) activities. Lead acetate treatment decreased GSH levels by 2-fold and the activities of GSH metabolizing enzymes decreased to a range of 2–2.5-fold in renal tissue (p?<?0.05). These changes were reversed significantly in animals receiving pretreatment of RT. Treatment of rats with RT prior to the treatment with lead resulted in the recovery of reduced levels of GSH, GSH-metabolizing enzymes to almost 85–90%. RT has a beneficial impact on lead-induced toxicity due to its scavenging and antioxidant effect in rats.     

Cardioprotective effects of rutin in rats exposed to pirarubicin toxicity

We established both an acute and chronic cardiac toxicity rat model, which showed pretreatment with rutin attenuated pirarubicin-induced myocardial histopathological injury, electrocardiogram abnormalities, and cardiac dysfunction. Rutin also significantly reduced serum levels of MDA, BNP, CK-MB, CTnT, and LDH and increased serum SOD levels. Treatment with rutin and dexrazoxane resulted in an increase in Bcl-2/Bax ratio (p < 0.05) and reduction in JNK and Caspase-3 protein levels, compared to the pirarubicin group (all p < 0.05). Furthermore, rutin at a dose of 50 mg/kg significantly attenuated the above-mentioned alterations. Our study suggests the antioxidant and anti-apoptotic properties of rutin may be responsible for the cardioprotective effects observed.     

Malathion-induced testicular toxicity in male rats and the protective effect of vitamins C and E

Sexually mature male Wistar rats (weighing 300–320 g and each group 6 animals) were given malathion (27 mg/kg; 1/50 of the LD₅₀ for an oral dose) and/or vitamin C (200 mg/kg) + vitamin E (200 mg/kg) daily via gavage for 4 weeks. The sperm counts, sperm motility, sperm morphology, FSH, LH, and testosterone levels, and histopathological changes in the testes of these rats, were investigated at the end of the 4th week. By the end of 4th week, rats given malathion alone, or in combination with vitamins C and E, had significantly lower sperm counts and sperm motility, and significantly higher abnormal sperm numbers, than the untreated control rats. The rats given malathion alone or in combination with vitamins also had significantly lower plasma FSH, LH and testosterone levels than the control rats. Co-treatment of malathion-exposed rats with vitamins E and C had a protective effect on sperm counts, sperm motility and abnormal sperm numbers, but not on plasma FSH, LH and testosterone levels. Light microscopic investigations revealed that 4 weeks of malathion exposure was associated with necrosis and edema in the seminiferous tubules and interstitial tissues. Degenerative changes in the seminiferous tubules were also observed in the rats which received malathion and supplemented with vitamins C and E, but milder histopathological changes were observed in the interstitial tissues. Thus, it appears that vitamins C and E ameliorate malathion testicular toxicity but are not completely protective.     

Evaluation of protective effect of vitamin e on acrylamide induced testicular toxicity in wister rats

Male wistar rats (weighting 160-180 g) were divided in six groups of 6 animals per group. Group A and F served as control. Groups B, C, D and E received acrylamide at 20 mg/kg body weight for 28 days and groups C and E received additionally vitamin E (50 IU/kg body weight) for 1 to 28 days and 29 - 42(nd) days of experiment, respectively. The animals from groups A, B, and C were sacrificed on day 28(th) of experiment and from groups D, E, and F on 42(nd) day of experiment, respectively. There was significant decrease in the total sperm count and significant increase in the dead sperm count on day 28(th) of study due to acrylamide toxicity. At recovery period, there was significant increase in the total sperm count of vitamin-E-treated group of animals as compared to untreated toxicated rats. But, values were significantly lower than control animals. Microscopically, the lesions in the testes of acrylamide intoxicated rats at 28(th) day revealed destruction of seminiferous tubules at periphery. No spermatid and spermatocytes were seen in the seminiferous tubules. Detachment of spermatogonial cells started at periphery of seminiferous tubules. Atrophy of seminiferous tubules was a constant finding. Some tubules showed vacuolar degenerative changes in germinal epithelium. During the recovery period, destruction of seminiferous tubules, detachment of spermatogonial cells, and atrophy of seminiferous tubules were observed in group D and E. Few sections revealed only spermatogonial cells. At recovery period vitamin-E-treated rats revealed somewhat better architecture of the seminiferous tubules. Late spermatids were seen in few seminiferous tubules and other revealed starting of spermatogenesis. Thus, it appears that Vitamin E is not able to protect testes from acrylamide toxicity during active feeding, but after cessation of acrylamide feeding treatment with vitamin E revealed faster recovery as compare to not treated group.     

Fifty-two week chronic toxicity of enzymatically decomposed rutin in Wistar rats

The chronic toxicity of enzymatically decomposed rutin, which consists mainly of isoquercitrin, was evaluated in male and female Wistar rats with dietary administration at concentrations of 0%, 0.04%, 0.2%, 1% and 5% for 52 weeks. No toxicological findings were found in the mortality, body weights, food consumption, hematology, clinical biochemistry or organ weights in either sex. Obvious clinical signs were chromaturia that could be attributed to the color of test substance in the 5% groups of both sexes. Coloration of the urine collected over 24 h in the 1% and 5% groups of both sexes was noted. Increased daily urinary calcium excretion was observed in the 5% groups of both sexes and an increase in urinary calcium concentration was observed in the male 5% group. On histopathological examination, incidences of mineralization, inflammatory cell debris, inflammatory cell infiltration and/or transitional cell hyperplasia in the renal pelvis were increased in the 5% male group, whereas treated females showed no apparent difference in these incidences. Based on the above findings, the no observed adverse effect level (NOAEL) was estimated to be 1% in both sexes (542.4 mg/kg body weight/day for males and 674.0 mg/kg body weight/day for females).     

Effects of rutin on acrylamide-induced neurotoxicity

Background

Rutin is an important flavonoid that is consumed in the daily diet. The cytoprotective effects of rutin, including antioxidative, and neuroprotective have been shown in several studies. Neurotoxic effects of acrylamide (ACR) have been established in humans and animals. In this study, the protective effects of rutin in prevention and treatment of neural toxicity of ACR were studied.

Results

Rutin significantly reduced cell death induced by ACR (5.46 mM) in time- and dose-dependent manners. Rutin treatment decreased the ACR-induced cytotoxicity significantly in comparison to control (P <0.01, P < 0.001). Rutin (100 and 200 mg/kg) could prevent decrease of body weight in rats. In combination treatments with rutin (50, 100 and 200 mg/kg), vitamin E (200 mg/kg) and ACR, gait abnormalities significantly decreased in a dose-dependent manner (P < 0.01 and P < 0.001). The level of malondialdehyde significantly decreased in the brain tissue of rats in both preventive and therapeutic groups that received rutin (100 and 200 mg/kg).

Conclusion

It seems that rutin could be effective in reducing neurotoxicity and the neuroprotective effect of it might be mediated via antioxidant activity.     

Developmental toxicity study of CBLB502 in Wistar rats

CBLB502 is a derivative of a microbial protein that binds to Toll-like receptor 5. It is demonstrated to reduce inflammatory response from acute stresses, such as radiation in animal models. We determined the potential developmental toxicity of CBLB502 in rats. Four groups of 25 time-mated female Wistar rats/group received subcutaneously 0, 30, 100, or 300 μg/kg/day of CBLB502 from Gestation Days (GD) 6 to 17 at a dose volume of 1.0 mL/kg. Toxicokinetic evaluation was performed on GD 6 and 17. On GD 20 C-section was performed for uterine evaluation and blood samples collected from each dam for immunogenicity assay.Significant decrease in gestation body weight, weight changes and food consumption indicative of maternal toxicity were observed in all dose groups. Also adjusted body weight and weight changes were seen at 300 μg/kg/day. No external, visceral and skeletal abnormalities were observed. The NOAEL for developmental toxicity was estimated to be ≥300 μg/kg/day.     

地塞米松的诱导效应对环磷酰胺大鼠毒性的影响

目的:观察地塞米松(dexamethasone,DEx)对大鼠细胞色素P450的诱导效应致环磷酰胺(cyclophos-phamide,CPA)对肝脏、肾脏、骨髓和膀胱毒性的影响.方法:雄性Wistar大鼠用DEX 50mg·kg-1·d-1诱导4d后,d5分别ip CPA 0,150和200mg·kg-1后36h,观察实验动物肝脏、肾脏、骨髓和膀胱毒性表现.结果:单独DEX诱导具有轻微的肝脏毒性.CPA单次给药造成骨髓细胞G2M期细胞的比例稍有升高,出现明显的尿蛋白和尿潜血.DEX的诱导作用增加了CPA的毒性:对肝毒性的增强作用主要表现在血浆ALT升高,肝脏总巯基和蛋白巯基含量降低,肝脏组织肝窦狭窄,肝小叶空泡变性;对肾脏毒性增强表现在血浆BUN和Cr升高,尿液蛋白和潜血增加,肾近端小管变性和髓质出血.DEX和CPA 200mg·kg-1合并用药组骨髓细胞的G0/G1期细胞增多,S期细胞明显减少.病理检查表明DEX和CPA合并用药组膀胱发生炎症和出血.结论:DEX诱导后使CPA对大鼠的肾脏、膀胱和骨髓毒性进一步增强,而DEX具有一定的肝脏毒性,与CPA合并给药后肝毒性有增强趋势.     

Long-term systemic toxicity of shikonin derivatives in Wistar rats

Context: Although the antitumor, immunomodulatory activities, and other effects of shikonin have been studied for decades, its systemic toxicity in vivo remains unclear.

Objective: To estimate the long-term systemic toxicity of shikonin derivatives (ShD) in a rat model.

Materials and methods: The roots of Arnebia euchroma (Royle) Johnst. (Boraginaceae) were extracted in ethanol, passed through a molecular sieve, and dried. A microemulsion solution in water was subsequently prepared. Adult Wistar rats were treated with ShD by gavage at concentrations of 200, 400, and 800?mg/kg per day for 90 days or 180 days. Hematological and biochemical examinations were performed, and the vital organs were subjected to pathological analyses.

Results: We did not observe hematological or non-hematological toxicity of ShD at a dose as high as 800?mg/kg per day for 6 months.

Discussion and conclusion: Our findings may offer some beneficial information for the practical application and research of Arnebia euchroma. We demonstrated in an animal model that ShD may be safe for usage.     

Evaluation of the toxicity of enzymatically decomposed rutin with 13-weeks dietary administration to Wistar rats.

The subchronic toxicity of enzymatically decomposed rutin, which consists mainly of isoquercitrin, was investigated in male and female Wistar rats with dietary administration at concentrations of 0, 0.2, 1 and 5% for 13 weeks. No mortality or abnormal clinical signs were observed throughout the experimental period in any groups. Body weight gain was reduced from week 10 to the end of the experiment in the 5% dosed males as compared to the 0% controls. Decreased erythrocytic parameters, i.e. red blood cell count, hemoglobin concentration and hematocrit, and significantly lowered serum triglyceride levels were also detected in the 5% males. Organ weight measurement, macro and microscopic observation revealed no test substance-related toxicological changes. Based on the above findings, no-observed-adverse-effect levels (NOAELs) for male and female rats were estimated to be 1 and 5%, respectively, translating into 539 and 3227 mg/kg b.w./day.     

Bioactive peptide carnosin protects against lead acetate-induced hepatotoxicity by abrogation of oxidative stress in rats

Context Oxidative stress is a common mechanism of liver injury. Carnosine is a dipeptide having strong antioxidant effects.

Objectives We investigated the effects of carnosine on lead-induced hepatotoxicity and oxidative stress in rats.

Materials and methods Animals received an aqueous solution of lead acetate (500?mg Pb/L in the drinking water) and/or daily oral gavage of carnosine (10?mg/kg) for 8 weeks. Rats were then weighed and used for the biochemical (commercial kits), molecular (standard chemical methods) and histological (microscopic) evaluations.

Results Lead-induced oxidative stress in liver tissue was indicated by a significant increase in the level of malondialdehyde (MDA) (8.25?±?0.15?nmol/mg) as well as decrease in the level of total antioxidant capacity (TAC) (1.72?±?0.25?μmol/g) and total thiol (SH) groups) 1.9?±?0.22?μmol/g). Carnosine treatment decreased MDA (4?±?0.08?nmol/mg), whereas it increased the contents of total thiol (3.25?±?0.04?μmol/g) and TAC (3.44?±?0.32?μmol/g) in the lead group. Carnosine also prevented the decreased body weight (p?<?0.001), albumin (p?<?0.05) and total protein levels (p?<?0.001) and increased liver weight (p?<?0.05) and activates of hepatic enzymes (p’s?<?0.001) (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase) in the lead group. Furthermore, histopathological study showed that carnosine attenuates liver damage by decreasing necrosis and infiltration of inflammatory cells.

Conclusion Carnosine prevented lead-induced hepatotoxicity, indicated by molecular, biochemical and histopathological analyses through inhibiting lipid peroxidation and enhancing antioxidant defence systems. Therefore, carnosine makes a good candidate to protect against the deleterious effect of chronic lead intoxication.     

A comprehensive evaluation of the testicular toxicity of dichlorvos in Wistar rats

Assessments of the reproductive toxicity of organophosphorus insecticides are important public health issues. This study aimed at defining the testicular toxicity of dichlorvos (DDVP) since this toxicity was suspected by our previous survey on pesticide sprayers and in some earlier publications during the 1970s. Ten-week-old Wistar rats were divided into four groups (n=8 or 9) and were injected subcutaneously with DDVP (0, 1, 2 or 4 mg/kg) 6 days a week for 9 weeks. After that period, erythrocyte cholinesterase (ChE) activities decreased dose-dependently, showing 44-55% inhibition among the treated groups. No significant difference was observed in the reproductive organ weights in any treated groups compared with the control group. Sperm motility decreased slightly but significantly in the 1 and 4 mg/kg groups, and significant regressions were observed between sperm motility and both blood ChE activity and urinary concentration of dimethyl phosphate (DMP), a urine metabolite of DDVP. However, sperm counts and sperm morphology in the cauda epididymidis, plasma testosterone concentrations, and histopathology in the testes in all the treated groups were not significantly different from those of the control group. Since only the sperm motility deteriorated by DDVP exposure at doses inducing marked inhibition of cholinesterase activities in the rats, it was suggested that the risk of testicular dysfunction posed to occupationally exposed humans would be small in terms of the effect of DDVP exposure alone. This conclusion was also supported by an estimate of the decrease in human sperm motility based on the urinary DMP concentrations observed in actual occupational settings.     

The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents

Introduction: Cyclophosphamide (CP) is an alkylating antineoplastic agent with known toxicity to the male reproductive system.

Areas covered: This review summarizes the known mechanisms by which CP exerts its toxic effects on the male reproductive system and the methods utilized to prevent such effects so that it could be further investigated and applied in clinical use. Keywords including [‘Cyclophosphamide’ AND ’male reproductive’ OR’ sperm toxicity’ OR ’spermatotoxicity’ OR ’infertility] were searched through Google Scholar, PubMed and Scopus databases based on PRISMA guidelines. After removing duplicates and irrelevant data, 76 papers were reviewed concerning the outcomes of treatment of male mice, rats, and humans with CP and the effects of co-administration of various natural and synthetic compounds on male reproductive system.

Expert opinion: CP exerts its effect mainly by inducing oxidative stress and changing gene expression in spermatocytes variably during different stages of development. These effects could be either restored or prevented by the administration of compounds with antioxidant properties and those which target the biochemical alterations induced by CP.     

Dose-dependent in-vivo toxicity assessment of silver nanoparticle in Wistar rats

This study aims to suggest the limits of silver nanoparticle (AgNP) uses for medicinal purpose and was performed to explore the effect of various doses of silver nanoparticle in rats. Four different doses of AgNP (4, 10, 20, and 40?mg/kg) were injected intravenously. For safety evaluation of injected AgNP, body weight, organ coefficient, whole blood count, and biochemistry panel assay for liver function enzyme (AST, ALT, ALP, and GGTP), comet assay, ROS, and histological parameter were performed; 10–12 week old animals were randomly divided into groups of six individuals each for control, and doses of 40, 20, 10, and 4?mg/kg AgNP injected. Significant changes were observed (p?<?0.01) in hematological parameters (WBC count, platelets counts, haemoglobin, and RBC count) in the 40 and 20?mg/kg groups. The changes were non-significant in the other groups (4 and 10?mg/kg group). In the 40?mg/kg group, a significant increase was also found in liver function enzymes like ALT and AST (p?<?0.01), ALP (p?<?0.01), GGTP (p?<?0.01), and bilirubin (p?<?0.01). ROS in blood serum increased in the high dose group. Tail migration in single cell gel electrophoresis in the 40, 20, 10, 4?mg/kg, and control groups was 34.9, 29.5, 17.8, 5.8, and 0.0 µm, respectively, which indicated damage in the DNA strand in the high dose group. EDXRF showed a ～ 10-times increase in silver concentration in the 40?mg/kg group and TEM image also showed particle deposition in the 40?mg/kg group. This study indicates that the AgNP in doses (< 10?mg/kg) is safe for biomedical application and has no side-effects, but its high dose (> 20?mg/kg) is toxic.     

荞麦花叶芦丁对小鼠酒精性肝损伤的保护作用

目的探讨荞麦花叶芦丁(RBFL)对小鼠酒精性肝损伤的保护作用。方法 72只小鼠随机均分为6组:正常组(A)、模型对照组(B)、三个剂量RBFL组(R1组:75 mg.kg-1.d-1;R2组:150 mg.kg-1.d-1;R3组:300 mg.kg-1.d-1)和RBFL标准品对照组(D组:150 mg.kg-1.d-1)。用50%乙醇按10 ml.kg-1.d-1连续灌胃10 d,制备小鼠酒精性肝损伤模型。测定血清AST、ALT活力,计算肝重指数(LI),测定肝组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,镜下观察肝组织病理改变来判断RBFL对酒精性肝损伤小鼠的保护作用。结果 RBFL不同程度地降低了酒精性肝损伤小鼠的死亡率和体重下降率,抑制肝损伤小鼠的LI、AST和MDA,显著增强肝损伤小鼠肝组织SOD活性;病理组织学显示,RBFL能显著改善酒精损伤肝细胞的形态学变化。结论 RBFL对小鼠酒精性肝损伤有显著的保护作用,其机制可能与抑制脂质过氧化损伤有关。     

硝酸羟胺急性、亚慢性染毒大鼠毒作用靶器官的研究

目的研究硝酸羟胺(hydroxylammonium nitrate,HAN)的急性毒性及亚慢性染毒大鼠后主要毒作用的靶器官。方法急性毒性实验中经腹腔对大鼠进行单次染毒,观察动物中毒症状,计算HAN的LD50和95%的可信限;亚慢性毒性实验中,分别以HAN 71、42、8 mg/kg不同剂量和生理盐水经腹腔染毒动物,连续染毒13周后脱颈椎处死3/4动物,剩余1/4动物停止染毒再饲养4周后同法处死,观察大鼠中毒症状和脏器的组织病理学改变,探讨HAN主要毒作用靶器官。结果HAN腹腔染毒大鼠的LD50为139.3 mg/kg,95%可信限为132.3~146.7 mg/kg。HAN亚慢性染毒后,动物体重无明显变化,各染毒组动物脾脏脏器系数明显高于对照组(P<0.05);组织病理学检查表明,HAN可引起含铁血黄素在体内的大量沉积,主要位于肝、脾和肾内,对组织脏器的损伤主要以氧化性损伤为主,主要靶器官为肺、肝、脾和肾。结论HAN属于中等毒性物质,长期接触对机体有一定的毒性作用。     

Prospective protective role of melatonin against arsenic-induced metabolic toxicity in Wistar rats

Subchronic exposure to arsenic is associated with alteration of glucose homeostasis. Arsenic treatment (as sodium arsenite) of male Wistar rats (weighing 130-150 g) at a dose of 5.55 mg kg(-1) body weight (equivalent to 35% of LD(50)) (i.p.) per day for a period of 30 days produced hypoglycemia, with associated increased urinary excretion of glucose and depletion of liver glycogen and pyruvic acid contents. Mobilization of free amino acids from kidney to liver was facilitated by arsenic treatment. Arsenic exposure significantly decreased the glutamate-pyruvate transaminase activity in kidney. Glucose 6-phosphatase activity in liver tissue was also significantly decreased after arsenic treatment. In addition to these, liver lactate dehydrogenase activity was elevated due to arsenic treatment. Melatonin supplementation (i.p.) at a dose of 10 mg kg(-1) day(-1) for last five days prior to sacrifice reversed most of the above changes caused by arsenic. Melatonin, being a potent free radical scavenger may reduce arsenic-induced free radical production, and thereby, eliminating its toxic effects. So, arsenic-induced hypoglycemia, with associated glycogenolytic as well as glycolytic activities of liver can be partially counteracted by melatonin supplementation. Accordingly, it may be suggested that melatonin can serve as a prospective protective agent against arsenic-induced metabolic toxicity.     

Repeated-doses and reproductive toxicity studies of the monoterpene 1,8-cineole (eucalyptol) in Wistar rats

1,8-cineole (eucalyptol) is widely used as an excipient in the pharmaceutical industry and as a food flavoring agent, thus providing significant potential for human exposure to the compound. We investigated the preclinical toxicity and reproductive toxicity of 1,8-cineole (CIN). In the repeated-doses toxicity study for 50 days, CIN (100, 500 or 1000 mg/kg) did not produce any signs of toxicity or deaths, but affected body weight gain during the first week of treatment. The hematological and biochemical profiles did not show significant differences except for increase in the MCV, platelet and urea levels or reduction in MCHC, MPV and alkaline phosphatase. Histopathological analysis showed weak changes in the lungs, liver, kidneys and uterus. In the reproductive toxicity, CIN (250, 500 or 1000 mg/kg) produced a reduction in body weight in pregnant rats treated during the pre-implantation or organogenesis periods. The highest doses induced a reduction in the mass of fetuses (pre-implantation) and dead fetuses (both periods) of pregnant rats. The results indicate that the treatment by repeated-doses showed occasional alterations in rats of both sexes. However, provide evidence that possibly 1,8-cineole presents maternal and fetal toxicity. This requires more detailed investigation to better characterize the toxic effects of this compound.     

芦丁神经保护作用的研究现状

芦丁是广泛存在于植物中的黄酮醇配体,具有抗氧化、抗炎、降压、维持血管弹性和神经保护等多种药理活性,在心脑血管疾病的治疗与预防起到至关重要的作用,有望可以改善或预防脑血管病、神经退行性病变及其他神经系统疾病.本文根据近年来的体内、外实验研究结果,综述了芦丁在缺血性脑卒中、阿尔茨海默病、帕金森病、抗癫痫和抗抑郁发挥脑神经保...     

Sensitive voltammetric determination of rutin at an in situ plated lead film electrode

A highly sensitive sensor for the determination of rutin by adsorptive stripping voltammetry was described. It consists of a lead film modified glassy carbon electrode (LF/GCE). In the proposed procedure rutin was accumulated by adsorption on the lead film electrode and then during the stripping step a lead film and the accumulated rutin were oxidised. The electrochemical behaviour of rutin at the lead film electrode was investigated by square-wave voltammetry. In the optimal conditions the anodic peak currents (measured by square-wave voltammetry) increased linearly with the concentration of rutin in the range of 5 × 10⁻¹⁰ to 1 × 10⁻⁸ mol L⁻¹. The detection limit for rutin following 30 s of accumulation time was equal to 2.5 × 10⁻¹⁰ mol L⁻¹. The method was successfully applied to the determination of rutin content in the tablets without previous separation.