Relative Kidney Weights Research Articles

A botanical from the antiproliferative Cameroonian spice, Imperata cylindrica is safe at lower doses, as demonstrated by oral acute and sub-chronic toxicity screenings

BackgroundThe cytotoxicity of the root’s methanol extract of Imperata cylindrica (ICR). was previously reported in a panel of human cancer cell lines, including multi-drug resistant phenotypes. The aim of this study was to assess the acute and sub-chronic oral toxicity of methanol root extract of Imperata cylindrica.MethodsThe acute toxicity was carried out according to the experimental protocol of OECD. The plant extract was administered orally to female rats at a single dose of 5000 mg/kg for 14 days and the animals were observed for any behavioral changes or mortality. For sub-chronic toxicity study, ICR was orally administered daily to male and female rats at different doses (250, 500 and 1000 mg/kg per b.w.) for 30 days. During these treatment days the animals were observed for any appearance of toxicity symptoms; following the treatment period, animals were sacrificed for hematological, biochemical and histopathology analysis.ResultsFrom the results of the acute oral toxicity assay, ICR was found to be non-toxic at the dose of 5000 mg/kg b.w. During the period of sub-chronic toxicity test, observation of signs, behavior and health status of the animals showed no abnormality in the groups of animals treated with ICR as compared to the controls. Significant variation of the relative body weights of heart and kidney were observed at dose a 1000 mg/kg b.w. Significant decrease of aspartate aminotransferase, creatinine level, low density lipoprotein concentration, triglyceride and total cholesterol were observed. In males, we noticed a significant decrease of the level of granulocytes with an increase of lymphocytes and mean corpuscular hemoglobin concentration levels. Histological examinations performed on kidney and liver showed a normal kidney architecture and liver also presented a normal hepatic architecture with slight degeneration at a dose 1000 mg/kg b.w.ConclusionICR is safe for acute oral administration; however, for long-term oral administration, safety measures should be taken. Thus, oral sub-chronic exposure of ICR at lower doses are recommended while higher doses around 1000 mg/kg b.w. should be discouraged.

Preventive effect of Stachys lavandulifolia against gentamicin-induced oxidative stress and nephrotoxicity in rats

Gentamicin (GM) is an effective antibiotic against gram-negative bacterial infection. However, GM can produce nephrotoxicity. Stachys lavandulifolia Vahl. (SL) is extensively used in folk medicine as herbal tea and has strong antioxidative effects. The aim of this study was to investigate the protective effect of SL on GM-induced nephrotoxicity in rats. In this study, forty-two male Wistar rats were randomly divided into six equal groups (N = 7 each): control (group I), GM-treated (group II), SL200 mg/kg + GM-treated (group III), SL400 mg/kg + GM-treated (group IV), SL200 mg/kg-treated (group V), and SL400 mg/kg-treated (group VI) groups. The treatment procedures continued for 10 days. At the end of the experiment, serum and the kidneys of all groups were harvested for histological and biochemical examination. No statistical significant improvement in histological and biochemical indices was shown at 200 mg/kg of SL treatment in group III compared with group II; however, at 400 mg/kg of SL, normalized serum levels of uric acid (P < 0.001), urea (P < 0.001), creatinine (P < 0.01), and total proteins (P < 0.05) were shown in group IV. Treatment with SL400 mg/kg also corrected the increased relative kidney weight in GM-treated animals (P < 0.05). GM nephrotoxicity was shown by elevated levels of malondialdehyde (P < 0.001) and decreased amounts of catalase (P < 0.001), superoxide dismutase (P < 0.01), and glutathione (P < 0.01) in renal tissue. The oxidative injury induced by GM was prevented by SL400 mg/kg treatment. Such treatment also normalized abnormal renal histology induced by GM. These data suggest that treatment with SL extract may be helpful to reduce gentamicin-induced nephrotoxicity.

Long-term vitamin D deficiency promotes renal fibrosis and functional impairment in middle-aged male mice.

Renal fibrosis is common especially in the elderly population. Recently, we found that vitamin D deficiency caused prostatic hyperplasia. This study aimed to investigate whether vitamin D deficiency promotes renal fibrosis and functional impairment. All mice except controls were fed with vitamin D-deficient (VDD) diets, beginning from their early life. The absolute and relative kidney weights on postnatal week 20 were decreased in VDD diet-fed male pups but not in female pups. A mild pathological damage was observed in VDD diet-fed male pups but not in females. Further analysis showed that VDD-induced pathological damage was aggravated, accompanied by renal dysfunction in 40-week-old male pups. An obvious collagen deposition was observed in VDD diet-fed 40-week-old male pups. Moreover, renal α-smooth muscle actin (α-SMA), a marker of epithelial-mesenchymal transition (EMT), and Tgf-β mRNA were up-regulated. The in vitro experiment showed that 1,25-dihydroxyvitamin D3 alleviated transforming growth factor-β1 (TGF-β1)-mediated down-regulation of E-cadherin and inhibited TGF-β1-evoked up-regulation of N-cadherin, vimentin and α-SMA in renal epithelial HK-2 cells. Moreover, 1,25-dihydroxyvitamin D3 suppressed TGF-β1-evoked Smad2/3 phosphorylation in HK-2 cells. These results provide experimental evidence that long-term vitamin D deficiency promotes renal fibrosis and functional impairment, at least partially, through aggravating TGF-β/Smad2/3-mediated EMT in middle-aged male mice.

Subchronic (90-Day) repeated dose toxicity study of disodium adenosine-5′-triphosphate in rats

Adenosine-5′-triphosphate (ATP) is the primary source of energy for cells and oral supplementation with ATP offers numerous different health benefits, including the regulation of blood flow and muscle contraction. In this study, ATP, disodium salt, was administered by gavage to rats for 90 consecutive days at doses of 0 (control), 500, 1000, and 2000 mg kg BW−1·d−1 (n = 10 per sex/group). Subchronic administration of ATP was well tolerated at all dose levels. Body weights and feed consumption body weight gains were similar between ATP-treated and control rats. Minor differences were seen in hematology and blood chemistry; however, these changes were not dose related and therefore not of biological or toxicological significance. Only one difference was observed in absolute organ weights, females of the high dose had increased kidney and increased relative kidney and liver weights; however, these differences were not seen in males nor appeared to be dose related. No biological or toxicological significant differences were observed in thyroid function or urine analysis. The incidence of histopathological lesions was low and similar between treated and control groups. Based upon these findings, the no-observed-adverse-effect level (NOAEL) was determined to be ≥ 2000 mg kg BW−1·d−1, which was the highest dose tested.

Oxidative stress and mitochondrial dysfunction involved in ammonia-induced nephrocyte necroptosis in chickens

Ammonia (NH3), an environmental pollutant, poses a serious threat to human and avian health. Although previous studies have showed that NH3 caused kidney injury, the molecular mechanisms of nephrotoxicity induced by NH3 remain unclear. To explore the mechanisms of NH3 nephrotoxicity, a total of 36 broiler chicks at one day of age were exposed to NH3. After 42 days of exposure, blood samples were collected to determine creatinine and uric acid; and kidney samples were weighted and then collected to detect ultrastructural changes, oxidative stress parameters, ATPases, necroptosis- and mitochondrial dynamics-related genes. The results showed that chickens exposed to NH3 showed lower relative kidney weight and an increase concentration in serum creatinine and uric acid. NH3 exposure caused nephrocyte necrosis and increased the expression of necroptosis-related genes (TNF-α, RIPK1, RIPK3, MLKL, and JNK). Besides, the activities of antioxidant systems (SOD, CAT, GSH-Px, and T-AOC) were reduced, whereas the concentrations of H2O2 and MDA were elevated. Lower activities of ATPases were obtained in NH3 treatment groups. Furthermore, the mitochondrial fission-related genes drp1 and mff were activated, and mitochondrial fusion-related genes opa1, mfn1 and mfn2 were suppressed after NH3 exposure. Based on the above results, we conclude that NH3 caused-oxidative stress and mitochondrial dysfunction mediated nephrocyte necroptosis in chickens. This study may provide new insight into NH3 nephrotoxicity.

Excessive dietary lead reduces growth performance and increases lead accumulation in pigs.

ObjectiveThe objective of this study was to investigate the influence of dietary lead (Pb) supplementation and feeding period on growth performance, organ weight, and Pb accumulation in pigs.MethodsIn a 56-day feeding experiment, a total of 48 barrows with initial body weight 10.4±0.6 kg were allotted to 2 dietary treatments (0 and 200 mg/kg of supplemental Pb) in a completely randomized design with 6 replicates. Body weight and feed intake were recorded to calculate growth performance. At the end of each 14 day-period (on days 14, 28, 42, and 56), an animal was randomly selected from each pen and slaughtered to collect blood samples, hair samples, left 5th rib, heart, liver, kidneys, lungs, and longissimus dorsi muscle samples.ResultsAverage daily gain and average daily feed intake were reduced (p<0.05) by supplemental Pb during the day 42 to 56. Relative kidney weight to body weight was linearly increased with increasing feeding period in pigs fed the Pb-supplemented diet, but not in pigs fed the control diet (p<0.05). The Pb concentrations in hair, left 5th rib, kidneys, and lungs were linearly increased with longer feeding period in pigs fed the Pb-supplemented diet, but not in pigs fed the control diet (p<0.01).ConclusionDietary Pb supplementation caused growth retardation and Pb accumulation in most organs, particularly in hair, bone, and kidneys in a time-dependent manner.

Sodium copper chlorophyllin attenuates adenine-induced chronic kidney disease via suppression of TGF-beta and inflammatory cytokines.

The present study was designed to evaluate the effect of sodium copper chlorophyllin (SCC) in adenine-induced chronic kidney disease (CKD). CKD was induced in male Wistar rats by feeding 0.3% w/w adenine diet for 28 days. After induction, animals were treated with sodium copper chlorophyllin at dose 2.7, 5.4, and 10.8 mg/kg for the next 28 days. The biochemical and urines parameters like creatinine, blood urea nitrogen (BUN), albumin, total protein creatinine clearance, urea clearance, and glomerular filtration rate were assessed on days 0, 14, and 28. Plasma TGF-β1, COX-2, and IL-6 levels were assessed. Various oxidative stress parameters and TGF-β1 expression were determined in the kidney. Histopathology of the kidney was studied with different stains. Sodium copper chlorophyllin-treated animals showed a significant reduction in urine output and relative kidney weight. The treatment with sodium copper chlorophyllin significantly improved kidney function by normalizing biochemical and urine parameters. Treatment with SCC significantly reduced circulatory inflammatory mediators-TGF-β1, COX-2, and IL-6. Additionally, the treatment also significantly reduced oxidative stress and TGF-β1 expression in kidney tissues. Histopathology studies showed inhibition in the kidney damage due to the treatment of SCC. The sodium copper chlorophyllin treatment attenuated adenine-induced chronic kidney disease in rats.

Response in carcass yield, organ weights, and gut morphology of broiler chickens to incremental levels of Vachellia tortilis leaf meal

The objective of this study was to assess the carcass yield, organ weights, and gut morphology response to Vachellia tortilis inclusion in broilers. Unsexed 14-d-old Cobb500™ chicks were randomly assigned to six diets containing 0, 30, 60, 90, 120, and 150 g kg−1 dry matter of V. tortilis leaf meal. The slaughter weight (SW), dressed carcass weight (DCW), breast weight, thigh weight (TW), drumstick weight (DW), and internal organs were measured. Villus height (VH), crypt depth (CD), epithelial, submucosa, and muscularis thickness were taken. The apparent villus surface area (AVSA) and villus to crypt ratio were calculated. There was a linear decrease in SW and DCW (P &lt; 0.05) with the increase of V. tortilis leaf meal. The SW and DCW decreased by 0.77 and 5.25 g for each g kg−1 increase in V. tortilis, respectively. The TW and DW showed no relationship with levels of V. tortilis leaf meal. The relative weight of gizzard, intestine, stomach, heart, and kidney increased linearly (P &lt; 0.05) as levels of V. tortilis increased. The relative weight of the liver was not related to V. tortilis inclusion. The VH, AVSA, VH to CD ratio, as well as submucosa, muscularis, and epithelial thicknesses linearly increased as the V. tortilis inclusion level increased. There was no relationship between V. tortilis leaf meal inclusion and CD (P &gt; 0.05). The increased morphological measurements suggest that leaf meal inclusion alters gut physiology and could influence the digestion and absorption of nutrients in broilers.

A 90-day repeated oral dose toxicity study of four stereoisomers of 2,4-dimethyl-4-phenyltetrahydrofuran, a synthetic flavoring substance, in F344 rats

2,4-Dimethyl-4-phenyltetrahydrofuran (CAS no. 82461-14-1) is a food additive used as a synthetic flavoring substance. To investigate the toxicological properties and determine the no-observed-adverse-effect level (NOAEL), a 90-day repeated oral dose toxicity study of 2,4-dimethyl-4-phenyltetrahydrofuran containing four stereoisomers was conducted in F344 rats at doses of 0, 6, 24, and 96 mg/kg body weight (BW)/day. No mortality or abnormal clinical signs related to treatment in any group was observed. At a dose of 96 mg/kg BW, fluctuated serum total protein and total cholesterol and increased absolute and relative liver weights and relative kidney weights were observed in both sexes. Increased serum albumin in males and decreased Na and Cl in females were also observed. On histopathological assessment, at a dose of 96 mg/kg BW, diffuse hepatocellular hypertrophy in the liver in both sexes and tubular regeneration with scattered proximal tubular degeneration and/or necrosis throughout the cortex in the kidney in males were detected. Based on these findings, the NOAEL for 2,4-dimethyl-4-phenyltetrahydrofuran used in the current study was found to be 24 mg/kg BW/day for both sexes.

Vannilic acid ameliorates hyperglycemia-induced oxidative stress and inflammation in streptozotocin-induced diabetic rats

ObjectiveDiabetes mellitus (DM) is a metabolic illness and it is a result of hyperglycemia ensuing since a deficiency in insulin production, insulin function. Based on WHO statistics, more than 347 million peoples are suffered from the DM globally and it may increase to 694 million in 2030. Vanillic acid (VA) is a phenolic derived compound from dietary vegetations and fruits with the many biological acitivities. This current research was planned to investigate the antidiabetic and anti-inflammatory potential of VA on streptozotocin-challenged DM in rats. MethodsLater than an overnight fast, the rats were induced diabetes via one intraperitoneal treatment of STZ (40 mg/kg b.wt) in a newly organized 0.1 M citrate buffer. We analyzed body weight, plasma glucose, liver marker enzymes, insulin, carbohydrate metabolic enzymes, glycosylated hemoglobin, protein profiles, oxidant/antioxidant levels, inflammatory mediators and also evaluate histopathology of pancreatic tissues in normal control and investigational animals. ResultsDiabetic animals were revealed an increased in HbA1c, blood glucose, food and fluid intake and relative weight of kidney and liver, whereas the reduced level of insulin and body weight. Furthermore, augmented levels of ALT, glucose-6-phosphatase, AST, TBARS, TNF-α, creatinine, LOOH, fructose 1,6-bisphosphatase, ALP, IL-6 and IL-1β whereas, reduced status of antioxidant enzymes were observed in diabetic rats. Histopathological analysis of pancreatic tissues was in support of the biochemical parameters. ConclusionsDiabetic rats treated by VA significantly alter all these parameters toward normal levels. These results recommended that the VA is a potential antidiabetic and anti-inflammatory effect for the cure of DM.

Protective effects of Avena sativa against oxidative stress-induced kidney damage resulting from an estrogen deficiency in ovariectomized Swiss mice model.

The aim of this study was to evaluate the antioxidant capacity of Avena sativa and to confirm its protective effects on estrogen deficiency in ovariectomized mice (OVX) model. Animals were treated during 21 and 60days as follows: negative control, positive control treated with oat, ovariectomized, and ovariectomized receiving hormonal or oat treatments, respectively. 21days post-surgery, our results showed that ovariectomy increases weight gain and urea level in plasma. After 60days of treatment, OVX showed a gain in weight, high increases in relative kidney weight, plasmatic creatinine, glutathione peroxidase (GPX) activity, and protein oxidation as shown by elevated protein carbonyl (PCO) and advanced oxidation protein products (AOPP) levels. On the other side, a decrease was detected in catalase activity. Meanwhile, no significant changes in urea level, lipid peroxidation, SOD and GSH activity were detected. Conversely, supplementation with oat reduced weight gain, as well as oxidative stress and oxidation protein in the kidney of OVX mice. PRACTICAL APPLICATIONS: In our study, we removed the two ovaries of adult female mice in order to eliminate the essential source of steroid hormones. Deficiency in these sexual hormones, especially estrogen, leads to several physiological and morphological disturbances that are found in post-menopausal women. The gain in weight and oxidative kidney damages were the main health problems detected in ovariectomized animals. This work explored for the first time the use of oat grains as a safe natural remedy to treat all previous health problems and to avoid carcinogenic effects of the menopausal hormone therapy. Owing to its health benefits, this cereal species has recently gained attention as an important source of antioxidants and fibers. Thanks to these two components, it can be able to restore all indicated disturbances. Therefore, this cereal can be very useful in the prevention of obesity and kidney oxidative damage occurring during menopause.

Effect of Levosimendan, an Inodilator, on Streptozotocin‐Induced Diabetic Nephropathy in Rats

Levosimendan, an inodilator, was shown to have a renal protective effect in different models of kidney dysfunction in experimental animals and in patients with heart failure. The aim of this study was to examine the effect of levosimendan on streptozotocin‐induced early diabetic nephropathy. Male Sprague Dawley rats (n = 24, 320–400 g) were randomly distributed into four groups and treated for 6 weeks. Groups 1 and 3 received either vehicle or levosimendan (1 mg/kg/day) for the last three weeks, respectively. Groups 2 and 4 were rendered diabetic by a single i.p. injection of streptozotocin (60 mg/kg) and were treated as in groups 1 and 3, respectively. At the end of the experiment, rats were placed in metabolic cages and urine was collected for biochemical analysis. Rats were then anesthetized and blood samples collected for biochemical analysis. Kidneys were removed for histopathology. In the untreated diabetic group, there was a significant decrease in body weight, polyuria and increased relative kidney weight. There was increased urinary albumin/creatinine ratio (UACR), 24 hour (h) albumin level and N‐acetyl‐β‐D‐glucosaminidase (NAG)/creatinine ratio (UNCR). Streptozotocin did not cause a significant effect on creatinine clearance when adjusted to body weight. In addition, diabetes was associated with increased oxidative stress [reduced plasma total antioxidant capacity (TAC) and catalase activities]. Kidneys from streptozotocin‐treated rats showed focal clear renal tubular cells affecting proximal convoluted tubules and focal mild interstitial fibrosis at the cortico‐medullary junction. Levosimendan significantly attenuated the reduction in body weight, polyuria and the increase in relative kidney weight. In addition, it significantly attenuated the increase in UACR, urinary 24 h albumin level and UNCR in diabetic rats. It also significantly mitigated the decrease in plasma TAC and catalase activities in diabetic rats. Rats in the diabetic group treated with levosimendan showed less clear cell changes but similar interstitial fibrosis when compared with the untreated diabetic group. This study shows that levosimendan ameliorated some of the changes seen in streptozotocin‐induced early diabetic nephropathy in rats. This could be partly due to its antioxidative effects.Support or Funding InformationSupported by an internal grant from Sultan Qaboos University (IG/MED/PHAR/18/01)

Study of immediate changes in blood coagulation in an experimental model of ischemia/reperfusion injury of the kidney

Abstract Introduction Ischemia- reperfusion injury (IRI) in the kidney triggers multifaceted network of plasma cascades including the complement, coagulation, kinins, and fibrinolytic system, which play major role in the reperfusion-triggered inflammatory process. Aim of the work The aim of the present study was to investigate changes in blood coagulation parameters immediately after ischemia and after ischemia/reperfusion of the kidney in adult rats of both sexes. Materials and Methods The study was carried out on 56 adult albino rats of both sexes weighing 160-220 gm. Rats were randomly allocated into 5 experimental groups as follows: Control rat group (C; n = 10). Sham1- operated rat group (SH1; n = 10) subjected to all the procedures of the I rat group except for renal ischemia and were sacrificed after 45 minutes. Ischemic rat group (I; n = 10) subjected to renal ischemia for 45 min, then were sacrificed. Sham 2 operated rat group 2 (SH2; n = 10) subjected to all the procedures of IR – rat group except for renal ischemia and reperfusion and were sacrificed after 1½ hour. Ischemic/reperfusion rat group (IR; n = 10) subjected to renal ischemia for 45 min, then reperfusion for 45 minutes, then were immediately sacrificed. All rats were subjected to estimation of body weight (BW), absolute and relative kidney weights (AKW and RKW), hemoglobin (Hb) and hematocrit (Ht.) values, clotting time, prothrombin time (PT), activated partial thromboplastin time (PTT), thrombin time (TT) and serum levels of urea (Ur.) and creatinine (Cr.). Results I rat group showed insignificant changes in AKW and RKW, CT, APTT, PT and TT compared to SH1 and C rat groups. However they showed significant elevation in Hb content, Ht. value and serum levels of Ur. and Cr. compared to C rat group. IR rat group showed significant increase in AKW and RKW compared to SH2, I and C rat groups. Also they showed significant increase in Hb. content, Ht. value and serum levels of Ur. and Cr. compared to C rat group. However they showed no significant change in their CT, APTT, PT and TT compared to SH2, I and C rat groups Conclusion Coagulation parameters are not changed immediately after kidney ischemic/reperfusion and may not contribute to the immediate pathophysiological changes of ischemic reperfusion injury.

Ameliorative Effect of Propolis Against Thioacetamide Induced Hepatorenal Injury in Adult Male Rats. Kidney Injury Molecule-1 (KIM-1) a Biomarker of Renal Injury

Abstract Background: Thioacetamide (TAA), a known industrial toxic agent, is extensively used in animal studies for induction of hepatic necrosis, fibrosis and cirrhosis, also reported to be nephrotoxic through induction of oxidative stress. Propolis, bee glue, is known by its antioxidant and anti-inflammatory properties. Aim of Study: This work aimed to evaluate the potential protective effect of propolis on TAA-induced hepatorenal damage and to evaluate the efficacy of Kidney Injury Molecuole-1 (KIM-1) in early detection of renal injury. Material and Methods: This study was performed on 24 adult male albino rats, divided into 3 groups; (I) Control group, (II) TAA-group (TAA was given in a dose of 50mg/kg /day intraperitoneally, 5 days/week for 2 weeks), (III) TAA-propolis treated group (TAA was given in the same way as in TAA-group, propolis was given in a dose of 500mg/kg/day by gavage, 5 days/week for 2 weeks). All studied rats were subjected to determination of initial and final body weight, body weight percent change, absolute and relative liver and kidney weight, as well as assessment of hepatic function by serum Alanine Transaminase (ALT) and Aspartate Transam-inase (AST), renal function by serum urea, creatinine and potassium (K+) level, with determination of renal tissue oxidative stress markers; Malondialdehyde (MDA) and Glu-tathione-S-Transferase (GST), inflammatory marker; Mye-loperoxidase (MPO), renal tissue damage marker; Kidney Injury Molecule-1 (KIM-1). In addition, specimens of liver and kidney were taken and processed for light microscopic studies. Results: TAA induced hepatotoxic and nephrotoxic effect that was evident by the significantly increased serum ALT, AST, urea and creatinine, with significant decrease in serum K+ level as well as significantly increased renal tissue MDA, GST, MPO and KIM-1 when compared with control group. Treatment with propolis caused significant reduction in serum ALT, AST, urea and creatinine, with significant elevation in serum K+ as well as significant reduction in renal tissue MDA, GST, MPO and KIM-1 when compared to the TAA group, but still significantly higher compared to controls except for urea. These results were confirmed by the histopathological findings. Conclusion: Propolis could partially ameliorate the TAA induced hepatorenal damage, which might be related to attenuation of oxidative stress and inflammation. Moreover, KIM-1 could be beneficial in detection of renal injury.

Risk assessment of chlorinated paraffins in feed and food.

The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of chlorinated paraffins in feed and food. The data for experimental animals were reviewed and the CONTAM Panel identified the liver, kidney and thyroid as the target organs for the SCCP and MCCP mixtures tested in repeated dose toxicity studies. Decreased pup survival and subcutaneous haematoma/haemorrhage were also identified as critical effects for an MCCP mixture. For the LCCP mixtures tested, the liver was identified as the target organ. The Panel selected as reference points a BMDL 10 of 2.3 mg/kg bw per day for increased incidence of nephritis in male rats, and of 36 mg/kg bw per day for increased relative kidney weights in male and female rats for SCCPs and MCCPs, respectively. For LCCPs, a reference point relevant for humans could not be identified. Due to the limitations in the toxicokinetic and toxicological database, the Panel concluded that derivation of a health‐based guidance value was not appropriate. Only limited data on the occurrence of SCCPs and MCCPs in some fish species were submitted to EFSA. No data were submitted for LCCPs. Thus, a robust exposure assessment and consequently a complete risk characterisation could not be performed. A preliminary risk characterisation based only on the consumption of fish was performed, and the calculated margins of exposure suggested no health concern for this limited scenario. The Panel noted that dietary exposure will be higher due to the contribution of CPs from other foods. The Panel was not able to identify reference points for farm animals, horses and companion animals. No occurrence data for feed were submitted to EFSA. Therefore, no risk characterisation could be performed for any of these animal species.

Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of Preeclampsia.

Aberrant production of hydrogen sulfide (H2S) has been linked to preeclampsia. We hypothesized that sodium thiosulfate (STS), a H2S donor, reduces hypertension and proteinuria, and diminishes fetal growth restriction in the Dahl salt-sensitive (S) rat, a spontaneous model of superimposed preeclampsia. In addition to a control group (n = 13), two groups received STS via drinking water at a dose of 2 g (n = 9) or 3 g per kg body weight per day (n = 8) from gestational day (GD) 10 to 20. Uterine artery resistance index was measured (GD18), urinary protein excretion rate was determined (GD19), and blood pressure and fetal outcomes were evaluated (GD20). At 2 g, STS had no effect on preeclamptic symptoms or fetal outcome. At 3 g, STS reduced maternal hypertension (121.8 ± 3.0 vs. 136.3 ± 2.9), but increased proteinuria (89 ± 15 vs. 56 ± 5 mg/24 h), and relative kidney weight (0.86 ± 0.04 vs. 0.73 ± 0.02%). Fetal/placental weight ratio was reduced (3.83 ± 0.07 vs. 4.31 ± 0.08) without affecting litter size. No differences in uterine artery flow or renal histological damage were noted across treatment groups. While these data suggest a promising antihypertensive effect that could imply prolongation of preeclamptic pregnancies, the unfavorable effects on proteinuria, kidney weight, and fetal/placental weight ratio implies that clinical implementation of STS is contra-indicated until safety for mother and child can be verified.

The Effect of Plectranthus amboinicus Lour Spreng Ethanolic Extract on Relative Organ, Body Weights Changes, and Hematology Profile in Wistar Rats Treated with 7,12Dimethylbenz(a)anthracene

This study aims to examine the protective properties of ethanol extract Plectranthus amboinicus (EEP) leaves on body weight gain, the relative weight of liver, kidney, lung, spleen, thymus and haematological profile of rats induced by 7,12Dimethylbenz(a)anthracene (DMBA). Used 25 female rats, divided into five groups namely NC (given Carboxymethyl cellulose (CMC) 1%), PC (given DMBA 20 mg/kg body weight), T1, T2, and T3 were each given DMBA 20 mg/kg body weight once every four days for 32 days and EEP 175, 350, and 700 mg/kg body weight given every day from day 33 to 59. Both the DMBA and EEP are given orally using a gastric gavage. On day 60, rats were killed by neck dislocation, bood collected in EDTA tubes for hematological analysis, rats are dissected to obtain liver, kidney, lung, thymus, and spleen organs. Data were analyzed with one way Analisys of varians (ANOVA). The results of this study indicate that EEP in T1, T2 and T3 treatments has no effect on weight loss compared to PC. There was no effect of EEP on the relative weight of the liver, kidneys, spleen, thymus and lungs. EEP increased the number of erythrocytes, leukocytes and platelets in rats that had DMBA

Biochemical and Hematological Effect of Cordyla pinnata Following Acute and Sub-Acute Exposure to Rattus norvegicus

Background: Cordyla pinnata (C. pinnata) is commonly used in traditional medicine for the treatment of various ailments. The aim of this study was to assess the toxic and safety potentials of the methanol extract of C. pinnata in rats. Methods: The methanol extract of C. pinnata was administered to the rats orally once daily at a dose of 0, 150, 300 or 600 mg/kg, body weight for 21 days. The toxicity was assessed using mortality rate, clinical signs, body and organ weights, hematological and serum chemistry indices. Results: The extract at 150, 300 or 600 mg/kg significantly decreased (p&lt;0.05) the serum alanine aminotransferase and sodium, but increased the urea concentration compared with those in the controls. There were no significant treatment-related alterations in the activities of aspartate aminotransferase, albumin, bilirubin, total proteins, chloride and creatinine. Also, the serum hematological parameters including Hemoglobin (HB), Packed Cell Volume (PCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentrations (MCHC) and Red Blood Cell (RBC) did not change significantly (p&lt;0.05). However, there were significant increases (p&lt;0.05) in White Blood Cell (WBC) and platelet counts, in weight gain and relative liver, kidney, lung and heart body weight ratio in the rats treated with 600 mg/kg of the extract compared with those in the controls. Conclusion: The C. pinnata extract was safe and non-toxic to the rats’ liver and blood components at doses up to 600 mg/kg for a period of 21 days. However, alterations found in the markers of kidneys integrity call for exercising caution when using this extract orally as a long-term remedy.

Co-therapeutic effects of metformin and Sidr fruits and leaves in experimental diabetic rats

Many diabetic patients prefer to use herbal medicine and treated with conventional drugs, concurrently. The main objective of this study was to evaluate the co-therapeutic effects of Sidr(Zizyphusspina-christi L.) fruits or leaves and metformin in diabetic rats. Forty two adult male albino rats were used and divided into seven groups (G1-G7). G1 was kept on basal diet (negative control), while other groups were subcutaneously injected with alloxan (120 mg/kg body weight).G2 was kept untreated as a positive control, while the other alloxan -injected groups were treated with metformin (100 mg/kg body weight) as a reference drug (G3), or fed on basal diet supplemented with 5% of either Sidr fruits (SFP) or leaves powder (SLP) (G4 and G5, respectively). G6 and G7 received combined treatments (metformin + SFP and metformin + SLP, respectively). The curative period lasted for 4 weeks. By its end, body weight gain (BWG) and relative weights of liver, kidneys and pancreas were calculated. Fasting glucose, insulin, amylase activity, liver glycogen, lipid profile as well as liver and kidney functions were determined. The typical manifestations of diabetes were noticed in untreated diabetic group including hyperglycemia and hypoinsulinemia.Moreover, a significant increase in serum amylase activity and relative liver and kidney weights was noticed associated with dyslipidemia, liver and kidney dysfunction and a significant decrease in BWG and absolute pancreas weight along with marked histopathological abnormalities in pancreas tissue.SFP was more effective than SLP in normalizing body weight, pancreas weight and liver antioxidant status, while the capability of SLP was higher in correcting the level of serum low density lipoprotein cholesterol (bad cholesterol). In general, receiving combined treatments was more efficient than receiving metformin alone.In conclusion, Sidr fruits and leaves can help metformin in the treatment of diabetes mellitus.

Embryonic cadmium exposure of male rats alters reproductive functions at adulthood, but without overt alterations in developmental and behavioral outcomes and metabolism

The effects of exposure of pregnant rats to cadmium (Cd) on the developmental and behavioral outcomes, reproductive functions, and metabolism of their male progeny were evaluated. Rats (Wistar) were injected intraperitoneally with either 0.5 or 5.0 µg Cd/kg body weight from day 12 to day 19 of pregnancy. The male offspring were evaluated for their developmental outcomes and behavioral changes. All developmental and behavioral parameters assessed were comparable among the different groups. All male pups were allowed to develop until 100 days of age and evaluated for reproductive end points. The results revealed that although the body weights and relative weights of liver, brain, kidney, testis, and epididymis were not altered, reproductive parameters, including daily sperm production, epididymal sperm numbers, and concentrations of motile, viable, and hypo-osmotic tail-swelled sperm declined significantly in rats exposed to 0.5 and 5.0 µg Cd during embryonic development. In addition, plasma testosterone levels and activity levels of testicular steroidogenic enzymes also decreased in these rats. In the fertility study, although each male in the 0.5, 5.0 µg, and control groups produced a copulatory plug and impregnated a female, the mean number of implantations and live fetuses was reduced significantly in females mated with rats exposed to 0.5 and 5.0 µg Cd during the prenatal period. The general metabolism of the animals exposed to Cd during embryonic development was comparable with the controls as evidenced by no significant changes in the activity levels of succinate dehydrogenase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, glutamate dehydrogenase, aspartate aminotransaminase, and alanine aminotransaminases in the liver, kidney, and testis. The results thus suggest that maternal Cd exposure during embryonic development markedly affected the spermatogenesis, steroidogenesis, and fertility potential, but without alterations in the development, behavior, and metabolism.