Ameliorative effects of Cnidoscolus aconitifolius on alloxan toxicity in Wistar rats

Background

Diabetes has been associated with several complications occasioned by oxidative stress. Thus, in treatment of the condition, these complications must also be taken into consideration. This study evaluates the effect of Cnidoscolus aconitifolius complications of diabetes induced by alloxan, on haematology and sperm morphometry using the Wistar rats.

Methods

Diabetes was induced in 25 rats using alloxan. The diabetic rats were then divided into five groups B–F consisting of five rats per group. Groups C–E were administered with 100mg/kg, 500mg/kg and 1000mg/kg of ethanolic leaves extract of Cnidoscolus aconitifolius, respectively, for four weeks post treatment with alloxan, while group F received Chlorpropamide (Diabenes®, Pfizer). The diabetic rats in group B were not treated while group A served as the non diabetic control.

Result

Following treatment with alloxan, there was anaemia, thrombocytopenia and leucopenia, while the sperm count, motility and live/dead ratio were significantly reduced. Sperm morphological abnormalities and erythrocyte osmotic fragility also increased significantly. Following treatment of alloxan treated-rats with the extract, there were significant increases in the PCV, RBC, Hb, WBC, MCV and the platelet values. Erythrocyte osmotic fragility, sperm count, motility and live/dead ratio also improved significantly.

Conclusion

Cnidoscolus aconitifolius extract was found to ameliorate the effects of alloxan induced diabetes on the haematology but not on the abnormal sperm morphometry in rats.     

Development of diabetes mellitus in the offspring of female rats with alloxan diabetes in six generations

S. M. Kirov Leningrad Postgraduate Medical Institute. Institute of Obstetrics and Gynecology, Academy of Medical Sciences of the USSR. I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR. Genetics Center, Leningrad. Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 105, No. 1, pp. 13–15, January, 1988.     

Antidiabetic effects of Corni Fructus extract in streptozotocin-induced diabetic rats

Purpose

Diabetes is the leading cause of end-stage renal failure. The present study was undertaken to characterize the effects of Corni Fructus on diabetic nephropathy in streptozotocin-induced diabetic rats and their mechanisms.

Materials and Methods

Streptozotocin-diabetic rats were orally administrated with Corni Fructus at a dose of 100, 200 or 400 mg/kg body mass for 40 days.

Results

Corni Fructus-treated diabetic rats showed significant decreases of blood glucose, urinary protein levels and water consumption. Corni Fructus also reduced serum total cholesterol, total triglyceride and low-density lipoprotein cholesterol levels, and showed a tendency of enhancing high-density lipoprotein cholesterol level. Levels of serum albumin and creatinine in diabetic rats were also significantly reduced by Corni Fructus administration at a dose of 200 and 400 mg/kg body mass compared with non-treated diabetic rats. Corni Fructus increased catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidose (GSH-px) activities in the kidneys of diabetic rats. Furthermore, Corni Fructus treatment enhanced renal peroxisome proliferator-activated receptor-γ (PPARγ) expression in diabetic rats.

Conclusion

These results demonstrated that Corni Fructus may have the potential to protect the animals from diabetic nephropathy by amelioration of oxidative stress and stimulation of PPARγ expression.     

Genetic variants of OCT1 influence glycemic response to metformin in Han Chinese patients with type-2 diabetes mellitus in Shanghai

Aims/hypothesis: Genetic variation in OCT1 can influence the glycemic response to metformin. We evaluated the effects of the OCT1 single-nucleotide polymorphisms (SNPs), rs1867351, rs4709400, rs628031, and rs2297374, on metformin efficacy in type-2 diabetes mellitus (DM) patients. Methods: We performed a single-center prospective analysis of the distributions of these SNPs in a cohort of Han Chinese subjects in Shanghai, China (HCS), and evaluated the effects of each SNP on glycemic control in HCS DM patients following 3 months of incident metformin treatment. Results: The allele frequencies of rs4709400 and rs628031 in our HCS control group differed from those previously reported for Han Chinese subjects in Beijing (HCB), as well as those previously reported for Caucasians and Africans, whereas the allele frequencies of rs1867351 and rs2297374 were more similar to those in HCB subjects. The DM patients with the rs1867351 T/T or rs4709400 G/G genotype exhibited greater reductions in postprandial plasma glucose (PPG), compared to those with different genotypes of these SNPs. The DM patients with the rs2297374 C/T, rs4709400 G/G, or rs628031 G/G genotype exhibited greater reductions in fasting plasma glucose (FPG), and those with the rs1867351 T/T, rs628031 A/A, or rs2297374 C/T genotype exhibited greater reductions in HbA_1c , compared to those with different genotypes of these SNPs. Conclusions /interpretation: The rs1867351, rs4709400, rs628031, and rs2297374 SNPs of OCT1 have selective effects on FPG, PPG, and HbA_1c in HCS DM patients in response to metformin treatment. Future studies of these SNPs in larger samples of HCS DM patients are warranted.     

Acute Effects of Aqueous Leaf Extract of Aspilia Africana C.D. Adams on Some Haematological Parameters in Rats

Several medicinal plants have been documented for their haematological effects either at low or high concentration but very little is known about Aspilia africana. The aim of the study was to investigate the acute effects of aqueous leaf extract of Aspilia africana at different concentrations on some haematological parameters in rats. Following 14 days of oral administration of aqueous extract of A. africana, Haematocrit (HCT), Haemoglobin concentration (HB), Mean Cell Haemoglobin Concentration (MCHC), Red Blood Cell Count (RBC Count), Total White Blood Cell Count (Total WBC Count), Absolute Neutrophils count (NEUT#), Absolute Lymphocytes count (LYM#), Absolute Eosinophils Count (EOSIN#) and Absolute Monocytes (MONO#) were evaluated in twenty (20) male Wistar albino rats. The rats weighed 174±20g, and were randomly assigned into 4 groups viz: Group 1, Control; Group 2, 250mg/Kg/d aqueous extract; Group 3, 500mg/Kg/d aqueous extract; and Group 4, 750mg/Kg/d aqueous extract. HCT, HB, MCHC, RBC Count, Total WBC Count, NEUT#, LYM#, EOSIN# and MONO# were significantly increased (P<0.001) in 500mg/Kg/d of A. africana extract (61.13±1.65%, 13.5±1.29g/dl, 23.33±0.0.02g/dl, 3.68±0.02 X 10¹²Cells/l, 2.33±0.02 X 10⁹Cells/l, 1.32±0.04 X 10⁹Cells/l, 1.43±0.05 X 10⁹Cells/l, 0.47±0.02 X 10⁹Cells/l and 0.47±0.04 X 10⁹Cells/l, respectively) when compared to the Control (51.13±0.85%, 9.56±0.43g/dl, 19.22±0.19g/dl, 2.69±0.01 X 10¹²Cells/l, 1.79±0.01 X 10⁹Cells/l, 0.80±0.00 X 10⁹Cells/l, 0.83±0.00 X 10⁹Cells/l, 0.18±0.00 X 10⁹Cells/l and 0.24±0.00 X 10⁹Cells/l, respectively) which received no extract at all. The 500mg/Kg of A. africana extract proved to be the most effective, while the 750mg/Kg proved to be the least effective in comparison with the control. The results of this study further strengthened the earlier works on the medicinal benefits of Aspilia africana and its virtue as a good pharmacological source of haematopoiesis.     

Remnant B-cell-stimulative and anti-oxidative effects of Persea americana fruit extract studied in rats introduced into streptozotocin - induced hyperglycaemic state

Insulin-stimulative and anti-oxidative effects of Persea americana fruit extract were evaluated using streptozotocin (STZ). Ethanol extract of P. americana in the concentration of 300 mg/kg body weight/rat /day was orally administered to rats introduced into STZ-induced hyperglycaemic state for a period of 30 days. After the treatment with avocado fruit extract, the elevated levels of blood glucose, glycosylated haemoglobin, blood urea and serum creatinine seen in the hyperglycaemic rats, reverted back to near normal. Similarly, significantly decreased plasma insulin and haemoglobin levels went back to near normal after the treatment, suggesting the insulin-stimulative effect of P. americana fruit. Determination of thiobarbituric acid reactive substances (TBARS), hydroperoxides and both enzymatic and non-enzymatic antioxidants, confirmed the anti-oxidative potential of avocado fruit extract which, in turn, might be responsible for its hypoglycaemic potential. Changes in activities of enzymes such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), and serum alkaline phosphatase (ALP) seen in the control and experimental rats, revealed the tissue-protective nature of Persea americana fruits, while all of the analysed biochemical parameters were comparable to those obtained with gliclazide as a standard reference drug.     

Effects of melatonin on DNA damage induced by cyclophosphamide in rats

The antioxidant and free radical scavenger properties of melatonin have been welldescribed in the literature. In this study, our objective was to determine theprotective effect of the pineal gland hormone against the DNA damage induced bycyclophosphamide (CP), an anti-tumor agent that is widely applied in clinicalpractice. DNA damage was induced in rats by a single intraperitoneal injectionof CP (20 or 50 mg/kg). Animals received melatonin during the dark period for 15days (1 mg/kg in the drinking water). Rat bone marrow cells were used for thedetermination of chromosomal aberrations and of formamidopyrimidine DNAglycosylase enzyme (Fpg)-sensitive sites by the comet technique and ofXpf mRNA expression by qRT-PCR. The number (mean ± SE) ofchromosomal aberrations in pinealectomized (PINX) animals treated with melatoninand CP (2.50 ± 0.50/100 cells) was lower than that obtained for PINX animalsinjected with CP (12 ± 1.8/100 cells), thus showing a reduction of 85.8% in thenumber of chromosomal aberrations. This melatonin-mediated protection was alsoobserved when oxidative lesions were analyzed by the Fpg-sensitive assay, both24 and 48 h after CP administration. The expression of XpfmRNA, which is involved in the DNA nucleotide excision repair machinery, wasup-regulated by melatonin. The results indicate that melatonin is able toprotect bone marrow cells by completely blocking CP-induced chromosomeaberrations. Therefore, melatonin administration could be an alternative andeffective treatment during chemotherapy.     

Reproductive effects of Ficus asperifolia (Moraceae) in female rats

The reproductive effects of Ficus asperifolia in female rats were investigated in the present study. Sperm-positive adult female rats were orally administered (P.O.) either the aqueous and methanol extracts of Ficus asperifolia (100 and 500mg/kg), distilled water (10ml/kg) or 5%Tween 80 (10ml/kg) for seven days. On day 10 of pregnancy, the implantation sites were recorded. In the fertility study, adult female rats received the same test substances for 21 days and, the fertility index and litter size determined. In the uterotrophic test, normal and ovariectomized immature rats were treated for seven days with the dry extract of Ficus asperifolia (100 and 500mg/kg) in the absence and presence of 17ȃ-estradiol benzoate 1µg/animal/day, s.c. On day 8, the uterine growth index was measured. Results of the study showed a significant increase (p<0.05) in the implantation sites and litter size of animals receiving 100mg/kg of the aqueous extract of Ficus asperifolia. In the estrogenic assay, normal immature rats were sensitive to the treatment with Ficus asperifolia than the ovariectomized ones. Our results give added scientific support to the popular use of Ficus asperifolia in the treatment of some cases of women''s sterility/infertility related problems.     

The protective effects of Ambroxol in Pseudomonas aeruginosa-induced pneumonia in rats

Introduction

To evaluate the effect of Ambroxol on the pulmonary surfactant (PS) in rat pneumonia induced by Pseudomonas aeruginosa (PA).

Material and methods

The pneumonic rats were obtained by injecting ATCC27853 intratracheally. One hundred and twenty SD rats were randomized into four groups: normal saline and Ambroxol was injected intraperitoneally following PA challenge in the PA/NS and PA/AM group; the other two groups were NS/AM and NS/NS. The wet/dry weight ratio (W/D), and pathological changes were assayed. Total proteins (TP), total phospholipid (TPL), and dipalmitoylphosphatidylcholine (DPPC) in bronchial alveolar lavage fluid (BALF) were analysed. Some BALF was cultured for colony counts. Ultrastructural change of the lung was observed by electron microscopy.

Results

The W/D ratio in the PA/AM group was lower than that in the PA/NS group; both were higher than that in the NS/NS group (p < 0.05). There were more neutrophils in the PA/NS group than in the PA/AM group (p < 0.05), and more in the PA/AM group than in the NS/NS group (p < 0.05). The ratio of DSPC/TPL and DSPC/TP in the BALF in PA/NS group was lower than that in the PA/AM group; DSPC/TPL and DSPC/TP ratios also increased in the NS/AM group. The PA colony numbers in the PA/AM group were lower than in the PA/NS group (p > 0.05). In the PA/NS group, vacuolation occurred in the lamellar body of alveolar type 2 cells (AT2) and the PS layer was rough and broken in some areas. In the PA/AM group, the degree of vacuolation of the lamellar body was less than in the PA/NS group.

Conclusions

Ambroxol could protect rats from pneumonia by improving the level of endogenous PS, especially DPPC.     

Synergistic Antiosteoporotic Effect of Lepidium Sativum and Alendronate in Glucocorticoid-Induced Osteoporosis in Wistar Rats

Alendronate belongs to a class of drugs called bisphosphonates. Bisphosphonates (BP) therapy is a vital option to reduce the risk of bone fracture in people who suffer from osteoporosis. Yet, bisphosphonate have displayed several side effects. Lepidium sativum (LS) seeds have been used in traditional folk medicine to heal fractured bones. However, there is a dearth of information on the impact of LS on bone metabolism especially in cases of glucocorticoids induced osteoporosis. Therefore, the aim of the study was to compare the biochemical bone markers and histological responses of LS alone (6 g of LS seeds in diet daily, n=8), ALD (alendronate, 70 mg/kg s.c.; n=8) alone, or LS and ALD combined in a rat model of glucocorticoid-induced osteoporosis (GIO) by injecting rats with methylprednisolone 3.5 mg/kg per day for 4 weeks. Serum calcium (Ca), albumin, phosphorus (P), bone-specific alkaline phosphatase (b-ALP), and tartrate-resistant acid phosphatase (TRAP) were measured 4 weeks after induction of GIO. GIO-group showed significantly increased serum TRAP and decreased b-ALP. GIO-group also showed significantly decreased serum P and unaltered Ca concentrations. Histological examination of GIO-group tibia bones indicated an osteoporotic change and a concomitant decrease in percentage of trabecular area or bone marrow area (PTB) in the proximal femoral epiphysis. Treatment with either LS and/or ALD ameliorated the above mentioned changes with variable degrees, with a net results of enhanced serum calcium, bone architecture, PTB, b-ALP and decreased TRAP in LS and LS+ALD groups compared to that of animals treated with alendronate alone. In conclusion, our findings present evidence supporting the potential benefits of LS in reducing the burden of GCs on bone health.     

Effect of interleukin-1β on platelet aggregation in August, Wistar, and WAG rats in acute emotional stress

Acute emotional stress inhibits platelet aggregation in August and WAG rats and reduces it in Wistar rats. Functional parameters of platelets are altered predominantly in passive rats. Interleukin-1β reduces the rate of platelet aggregation in nonstressed August and WAG rats and elevates it in Wistar rats. Preliminary injection of interleukin-1β reduces the stress-induced changes in platelet aggregation in August and WAG rats; while in Wistar rats this effect is not observed. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 8, pp. 144–147, August, 1997     

Anti Cancerous Efficacy of Ayurvedic Milk Extract of Semecarpus Anacardium Nuts on Hepatocellular Carcinoma in Wistar Rats

The objective of the study was to determine the anticancerous efficacy of Ayurvedic preparation made of Semecarpus anacardium (SA) nuts. Five groups of rats were used for the study. Group I served as water control. Hepatocellular carcinoma (HCC) was induced in groups II, III and IV animals using N-nitrosodiethylamine as inducing agent followed by phenobarbitone as promoter for 13 weeks. Group-II animals were kept untreated as hepatocellular carcinoma control. Group-III animals were treated with Ayurvedic milk extract of Semecarpus anacardium nuts at dose mentioned in Ashtangahridaya, an authentic book of Ayurveda for 49 days and group-IV animals were treated with doxorubicin as reference drug at dose of 1mg/kg twice a week for 7 weeks. Group V animals were kept as drug (SA nut milk extract) control for studying the effect of nut milk extract on normal rats. After 154 days of experiment, all animals were subjected to screening for HCC by estimation of liver enzymes, HCC marker (alpha-2 macroglobulin) and histopathology. Both liver enzymes and HCC marker were increased in hepatocellular carcinoma control along with neoplastic changes in liver and were decreased in Semecarpus anacardium nut milk extract treated group. The Ayurvedic drug showed positive correlation with the action of doxorubicin. This study demonstrated the efficacy of Semecarpus anacardium nut milk extract for the treatment of hepatocellular carcinoma either alone or along with chemotherapy.     

Mechanisms of the antihypertensive effects of Nigella sativa oil in L-NAME-induced hypertensive rats

OBJECTIVESThis study was conducted to determine whether the blood pressure-lowering effect of Nigella sativa might be mediated by its effects on nitric oxide, angiotensin-converting enzyme, heme oxygenase and oxidative stress markers.METHODS:Twenty-four adult male Sprague-Dawley rats were divided equally into 4 groups. One group served as the control (group 1), whereas the other three groups (groups 2-4) were administered L-NAME (25 mg/kg, intraperitoneally). Groups 3 and 4 were given oral nicardipine daily at a dose of 3 mg/kg and Nigella sativa oil at a dose of 2.5 mg/kg for 8 weeks, respectively, concomitantly with L-NAME administration.RESULTSNigella sativa oil prevented the increase in systolic blood pressure in the L-NAME-treated rats. The blood pressure reduction was associated with a reduction in cardiac lipid peroxidation product, NADPH oxidase, angiotensin-converting enzyme activity and plasma nitric oxide, as well as with an increase in heme oxygenase-1 activity in the heart. The effects of Nigella sativa on blood pressure, lipid peroxidation product, nicotinamide adenine dinucleotide phosphate oxidase and angiotensin-converting enzyme were similar to those of nicardipine. In contrast, L-NAME had opposite effects on lipid peroxidation, angiotensin-converting enzyme and NO.CONCLUSION:The antihypertensive effect of Nigella sativa oil appears to be mediated by a reduction in cardiac oxidative stress and angiotensin-converting enzyme activity, an increase in cardiac heme oxygenase-1 activity and a prevention of plasma nitric oxide loss. Thus, Nigella sativa oil might be beneficial for controlling hypertension.     

Effect of phentolamine and obsidan on morphometric indices of the islets of Langerhans in rats receiving alloxan

Chronic administration of phetolamine and obsidan to rats previously treated with alloxan alleviated the destructive action of alloxan on the B cells and promoted new islet formation. It is suggested that phentolamine and obsidan block one of the possible mechanisms of the destructive action of alloxan on the islet tissue, connected with the intensification of adrenalin secretion.Department of Human and Animal Physiology, N. G. Chernyshevski Saratov University. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 11, pp. 582–584, November, 1977.     

Effect of pollen typhae on inhibiting autophagy in spinal cord injury of rats and its mechanisms

Purpose: To investigate the effects and mechanism of pollen typhae on spinal cord injury (SCI) in rats. Methods: The SCI model was built and animals were randomly divided into three groups according to different concentrations of pollen typhae. Protein, mRNA, and fluorescence expression levels of light-chain-3 (LC-3) and Beclin-1 were determined by western blotting (WB), real-time PCR and immunofluorescence, along as Akt and mammalian target of rapamycin (mROT) by WB. The demyelination area and integrated optical density (IOD) were analyzed by luxol fast blue (LFB) and Nissl staining, respectively; Behavioral assessments were assessed by Basso Beattie Bresnahan (BBB) scale. Results: Protein, mRNA, and fluorescence expression levels of LC-3 and Beclin-1 were significantly increased after SCI, while were obviously decreased by administration of pollen typhae, along with protein level of Akt and mROT. The demyelination area was significantly reduced, while IOD and BBB were significantly increased compared with the model group. Conclusion: Autophagic activity increased in damaged neural tissue after SCI, and pollen typhae have certain therapeutic effect on SCI, the higher concentration of pollen typhae, the more effective. Besides, pollen typhae also provided neuroprotective effect and improved locomotor function. The effects may be produced by blockade of Akt/mTOR pathway.     

Acute and subchronic oral toxicities of Calendula officinalis extract in Wistar rats

We have studied the acute and subchronic oral toxicities of Calendula officinalis extract in male and female Wistar rats. A single acute C. officinalis extract dose of 2000 mg/kg dissolved in distilled water was administered by oral gavage for acute toxicity. Subchronic doses of 50, 250 and 1000 mg/kg/day were administered in drinking water. The major toxicological endpoints examined included animal body weight, water and food intake, selected tissue weights, and histopathological examinations. In addition, we examined blood elements: hematocrit, hemoglobin concentration, erythrocyte count, total and differential leukocyte count and blood clotting time and blood chemistry: glucose, total cholesterol, urea, total proteins, alkaline phosphatase, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In the acute study, there were no mortality and signs of toxicity. In the subchronic study, several of the blood elements were significantly affected in males and females after 90 days; hemoglobin, erythrocytes, leukocytes and blood clotting time. For blood chemistry parameters, ALT, AST and alkaline phosphatase were affected. Histopathological examination of tissues showed slight abnormalities in hepatic parenchyma that were consistent with biochemical variations observed. These studies indicate that the acute and subchronic toxicities of C. officinalis extract are low.     

An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

ABSTRACT Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m (^99mTc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na^99mTcO₄) in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na^99mTcO₄ and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na^99mTcO₄ in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na^99mTcO₄ are conducted in patients who are using senna extract.