scholarly journals Preliminary toxicology profile of Dennettia tripetala (Pepper Fruit) methanolic leaves extract

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Joseph Chukwufumnanya Mordi ◽  
Patrick Chukwuyenum Ichipi-Ifukor ◽  
Godfery Rume Kweki ◽  
Rita Ngozi Ichipi-Ifukor ◽  
John Chukwuma Oyem ◽  
...  

Abstract Background Dennentia tripetalla (Pepper Fruit) belongs to the Annonaceae family and is abundant in Nigeria. Its fruit in folklore medicine is used for treatment of varying ailments. While ample research evidence exists on the plants fruit and seed, no current study exists on the toxicological profile of the plant leaves. Methods qualitative and quantitative phytochemicals and In vitro antioxidant assays were carried out using standard methods. The acute toxicity study indicates that the LD50 was higher than 2000 mg/Kg body weight. Sub-chronic toxicity studies was carried out using five groups of rats. Group 1 served as control, 2–5 received 100 mg/Kg, 200 mg/Kg, 500 mg/Kg and 1000 mg/Kg body weight orally for 28 days. Results Post-administration biochemical analysis indicates there was increased weight in rats administered 100 mg/kg and 200 mg/kg while it reduced in the 500 mg/kg group. Significant elevations of liver function markers were reported for 200 mg/kg and 500 mg/kg respectively. Serum and hepatic protein profiles remained unaltered. Renal function analysis revealed elevated serum urea and creatinine for 200 and 500 mg/kg groups, elevated serum Na+ and Ca+ and reduced serum Cl− for the 500 mg/Kg group. Elevated Kidney K+ and Ca+ levels, reduced Cl− were significantly observed in 500 mg/Kg group. Significant rise in hepatic and renal lipid peroxidation was observed in 200 and 500 mg/Kg groups. There were observed disarmament of the antioxidant defense systems occasioned by rise and drop in tissue (hepatic, renal, testes, heart) Superoxide dismutase (SOD), Catalase (Cat), Glutathione-s-transferase (GST), Glutathione peroxidase (GPx) activities in the test groups relative to control. Histopathological examination indicated architectural aberrations at 500 and 1000 mg/kg. Conclusions It concluded that the plant had significant phytochemical and antioxidant properties of medical interest and possessed toxic properties in rats when administered at a dose above 200 mg/Kg over a prolonged period of time.

2012 ◽  
Vol 67 (5-6) ◽  
pp. 297-307 ◽  
Author(s):  
Osama M. Ashour ◽  
Ashraf B. Abdel-Naim ◽  
Hossam M. Abdallah ◽  
Ayman A. Nagy ◽  
Ahmed M. Mohamadin ◽  
...  

Doxorubicin (DOX) is an anthracycline antibiotic widely used as a chemotherapeutic agent in the treatment of several tumours. However, its cardiac toxicity limits its use at maximum therapeutic doses. Most studies implicated increased oxidative stress as the major determinant of DOX cardiotoxicity. The local Saudi flora is very rich in a variety of plants of quite known folkloric or traditional medicinal uses. Tribulus macropterus Boiss., Olea europaea L. subsp. africana (Mill.) P. S. Green, Tamarix aphylla (L.) H. Karst., Cynomorium coccineum L., Cordia myxa L., Calligonum comosum L’ Hér, and Withania somnifera (L.) Dunal are Saudi plants known to have antioxidant activities. The aim of the current study was to explore the potential protective effects of methanolic extracts of these seven Saudi plants against DOX-induced cardiotoxicity in rats. Two plants showed promising cardioprotective potential in the order Calligonum comosum > Cordia myxa. The two plant extracts showed potent in vitro radical scavenging and antioxidant properties. They significantly protected against DOX-induced alterations in cardiac oxidative stress markers (GSH and MDA) and cardiac serum markers (CK-MB and LDH activities). Additionally, histopathological examination indicated a protection against DOX-induced cardiotoxicity. In conclusion, C. comosum and C. myxa exerted protective activity against DOX-induced cardiotoxicity, which is, at least partly, due to their antioxidant effect


1972 ◽  
Vol 52 (3) ◽  
pp. 497-505 ◽  
Author(s):  
R. D. G. MILNER ◽  
M. A. ASHWORTH ◽  
A. J. BARSON

SUMMARY Pieces of pancreas from human foetuses of 14–24 weeks gestational age and weighing between 50 and 625 g were incubated in vitro. Insulin release was studied under control conditions and in media supplemented with glucose (3 mg/ml), leucine (5 mmol/1) or arginine (5 mmol/1). Glucose never caused a significant rise in insulin release from the pancreas. The failure of mannoheptulose (3 mg/ml) and 2-deoxyglucose (3 mg/ml) to suppress basal insulin release in a glucose-free medium indicated that basal insulin release was not governed by the liberation of glucose from glycogen in the exocrine pancreas. Arginine stimulated insulin release in four experiments using pancreas from foetuses weighing more than 200 g, but failed to cause insulin release from the pancreas of foetuses weighing less than 200 g in three experiments. Leucine consistently stimulated insulin release from the pancreas of foetuses of less than 200 g body weight but was only variably effective in causing insulin release from pancreas of foetuses weighing more than 200 g. The experimental results illustrate the development of different mechanisms for the release of insulin from the human foetal β cell.


Blood ◽  
2001 ◽  
Vol 98 (13) ◽  
pp. 3693-3698 ◽  
Author(s):  
Meira Melamed-Frank ◽  
Orit Lache ◽  
Benjamin I. Enav ◽  
Tal Szafranek ◽  
Nina S. Levy ◽  
...  

Abstract Haptoglobin serves as an antioxidant by virtue of its ability to prevent hemoglobin-driven oxidative tissue damage. It was recently demonstrated that an allelic polymorphism in the haptoglobin gene is predictive of the risk for numerous microvascular and macrovascular diabetic complications. Because these complications are attributed in large part to an increase in oxidative stress, a study was conducted to determine whether the different protein products of the 2 haptoglobin alleles differed in the antioxidant protection they provided. A statistically significant difference was found in the antioxidant capacity of purified haptoglobin protein produced from the 2 different alleles, consistent with the hypothesis that differences in genetically determined antioxidant status may explain differential susceptibility to diabetic vascular complications. These differences may be amplified in the vessel wall because of differences in the sieving capacity of the haptoglobin types. Therefore, an attempt was made to identify the minimal haptoglobin sequences necessary to inhibit oxidation by hemoglobin in vitro, and 2 independent haptoglobin peptides that function in this fashion as efficiently as native haptoglobin were identified. Identification of the biochemical basis for differences among haptoglobin types may lead to the rational development of new pharmacologic agents, such as the mini-haptoglobin described here, to avert the development of diabetic vascular complications.


2013 ◽  
pp. 663-670 ◽  
Author(s):  
T. SZKUDELSKI ◽  
A. ZYWERT ◽  
K. SZKUDELSKA

Rats with diabetes induced by streptozotocin (STZ) and nicotinamide (NA) are often used in animal studies concerning various aspects of diabetes. In this experimental model, the severity of diabetes is different depending on doses of STZ and NA. Moreover, diabetic changes in rats with STZ-NA-induced diabetes are not fully characterized. In our present study, metabolic changes and insulin secretion were investigated in rats with diabetes induced by administration of 60 mg of STZ and 90 mg of NA per kg body weight. Four to six weeks after diabetes induction, insulin, glucagon and some metabolic parameters were determined to evaluate the severity of diabetes. Moreover, insulin secretory capacity of pancreatic islets isolated from control and diabetic rats was compared. It was demonstrated that administration of 60 mg of STZ and 90 mg of NA per kg body weight induced relatively mild diabetes, since insulin, glucagon and other analyzed parameters were only slightly affected in diabetic rats compared with control animals. In vitro studies revealed that insulin secretory response was preserved in pancreatic islets of diabetic rats, however, was lower than in islets of control animals. This effect was observed in the presence of different stimuli. Insulin secretion induced by 6.7 and 16.7 mmol/l glucose was moderately reduced in islets of diabetic rats compared with control islets. In the presence of leucine with glutamine, insulin secretion appeared to be also decreased in islets of rats with STZ-NA-induced diabetes. Insulinotropic action of 6.7 mmol/l glucose with forskolin was also deteriorated in diabetic islets. Moreover, it was demonstrated that at a non-stimulatory glucose, pharmacological depolarization of plasma membrane with a concomitant activation of protein kinase C evoked significant rise in insulin release in islets of control and diabetic rats. However, in diabetic islets, this effect was attenuated. These results indicate that impairment in insulin secretion in pancreatic islets of rats with mild diabetes induced by STZ and NA results from both metabolic and nonmetabolic disturbances in these islets.


2018 ◽  
Vol 12 (3) ◽  
pp. 9-13
Author(s):  
Mehrzad Bahtouee ◽  
◽  
Hossein Fatemikia ◽  
Ali Movahed ◽  
Abdolhamid Esmaili ◽  
...  

Background: The purpose of this study was to compare the effects of saffron and methylprednisolone on bleomycin-induced pulmonary fibrosis in rats. Methods: This study was conducted in Bushehr, southern Iran in 2017.The animals were divided into four groups of five rats each. Three groups were injected with a single intratracheal dose of bleomycin (5 mg/kg). The fourth group was administered with normal saline at the same volume (200 µl). Saffron extract dissolved in water was given to one group (100 mg /body weight) orally while intraperitoneal injection of methylprednisolone (2.5 mg/kg) injected to another one for 16 days. The rats were sacrificed 28 days following surgery and their right and left lungs were removed and washed for measuring lung indices, myeloperoxidase activities and finally histopathological examination. Results: Injection of bleomycin caused decrement of body weight aggravated by intraperitoneal methylprednisolone treatment. Lung indices were increased in the bleomycin-treated group compared with the control, while methylprednisolone, unlike saffron, had no preventive effects on it. Both saffron and methylprednisolone treatment prevented the increase in lung myeloperoxidase as a destructive enzyme. In addition, excessive collagen deposition and thickening of alveolar septa were significantly prevented with saffron treatment as compared to methylprednisolone injection following hematoxylin and eosin staining. Conclusion: Saffron with established antioxidant properties could prevent some detrimental effects in bleomycin-induced pulmonary fibrosis even more than methylprednisolone injection known as a standard therapy in this murine model. More investigations must be carried out to examine the beneficial or harmful effects of this remedy.


Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2502 ◽  
Author(s):  
Joanna Tkaczewska ◽  
Ewelina Jamróz ◽  
Ewa Piątkowska ◽  
Barbara Borczak ◽  
Joanna Kapusta-Duch ◽  
...  

Carp skin gelatine hydrolysate (CSGH) may be a possible bioactive peptide source, as promising antioxidant properties have been noted during in vivo testing. Hence, the present study focused on improving the bioavailability of the antioxidant peptides from CSGH and on the use of furcellaran (FUR), which can protect the biopeptides during digestion in the gastrointestinal tract. Therefore, in this study, microcapsules coated with furcellaran and containing CSGH cores were prepared. The structural properties of the sample were determined using FT-IR and SEM analysis. The antioxidant properties of hydrolysate, uncoated, and encapsulated samples were investigated. In vivo analysis included determination of its safety in an animal organism and evaluation of the lipid profile, antioxidant blood status, and mRNA expression of some genes involved in antioxidant status in Wistar rats. The results showed no adverse effects of microencapsulated protein hydrolysates in laboratory animals. Nonetheless, there was a statistically significant rise in the level of total antioxidant status blood serum among animals consuming CSGH and not inducing oxidative stress. This can be viewed as a promising indication of the positive effects of antioxidant properties tested in vivo. The process of CSGH microencapsulation in FUR cause a decrease in antioxidant hydrolysate activity, both in vitro, as well as in healthy Wistar rats. When considering the results of the presented diverse therapeutic potential, further research on CSGH being a potential bioactive peptide source used as a functional food or nutraceutical, but with a different microencapsulation coating, is encouraged.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 195
Author(s):  
Yaswanth Kuthati ◽  
Prabhakar Busa ◽  
Srikrishna Tummala ◽  
Vaikar Navakanth Rao ◽  
Venkata Naga Goutham Davuluri ◽  
...  

Oxidative stress resulting from reactive oxygen species (ROS) is known to play a key role in numerous neurological disorders, including neuropathic pain. Morphine is one of the commonly used opioids for pain management. However, long-term administration of morphine results in morphine antinociceptive tolerance (MAT) through elevation of ROS and suppression of natural antioxidant defense mechanisms. Recently, mesoporous polydopamine (MPDA) nanoparticles (NPS) have been known to possess strong antioxidant properties. We speculated that morphine delivery through an antioxidant nanocarrier might be a reasonable strategy to alleviate MAT. MPDAs showed a high drug loading efficiency of ∼50%, which was much higher than conventional NPS. Spectral and in vitro studies suggest a superior ROS scavenging ability of NPS. Results from a rat neuropathic pain model demonstrate that MPDA-loaded morphine (MPDA@Mor) is efficient in minimizing MAT with prolonged analgesic effect and suppression of pro-inflammatory cytokines. Additionally, serum levels of liver enzymes and levels of endogenous antioxidants were measured in the liver. Treatment with free morphine resulted in elevated levels of liver enzymes and significantly lowered the activities of endogenous antioxidant enzymes in comparison with the control and MPDA@Mor-treated group. Histopathological examination of the liver revealed that MPDA@Mor can significantly reduce the hepatotoxic effects of morphine. Taken together, our current work will provide an important insight into the development of safe and effective nano-antioxidant platforms for neuropathic pain management.


2007 ◽  
Vol 31 (2) ◽  
pp. 252-263 ◽  
Author(s):  
Haibo Sha ◽  
Jingyue Xu ◽  
Jing Tang ◽  
Jun Ding ◽  
Jianfeng Gong ◽  
...  

Mutants of brain-derived neurotrophic factor (BDNF) are associated with obesity. However, the regulatory mechanism of BDNF expression is still unclear. We developed a novel mutant mouse line, transgenic insertional mutants with obesity, named Timo, in which a potential regulatory locus of Bdnf was disrupted by transgene insertion. The insertion site was identified and lies 857 kb upstream of the Bdnf gene. The disrupted genomic locus is conserved across the mouse, rat, dog, and human genome and contains several highly conserved elements that are able to upregulate reporter gene expression in vitro. Along with downregulation of BDNF to ∼30% of wild-type animals, Timo/ Timo mice exhibited increased body weight and fat content with hepatic steatosis and elevated serum levels of leptin, cholesterol, and LDL cholesterol. These mutant mice also showed obesity-independent insulin resistance, hyperinsulinemia, impaired glucose tolerance, age-dependent hyperglycemia, and shortened life span. Molecular and phenotype analysis of Timo/ Timo mice indicated the existence of a genome locus, lying 857 kb upstream of the Bdnf gene, that regulates BDNF expression, body weight, and glucose homeostasis.


2014 ◽  
Vol 42 (01) ◽  
pp. 189-206 ◽  
Author(s):  
Mohammed S. Al-Dosari

The widely used culinary vegetable, red cabbage (Brassica oleracea L. Var. capitata f. rubra), of the Brassicaceae family contains biologically potent anthocyanins and a myriad of antioxidants. Previous studies have shown that the pharmacological effects of red cabbage in vivo are redox-sensitive. The present study explored whether red cabbage modulates various histopathological and biochemical parameters in rats administered with a cholesterol-rich diet (CRD). To this end, prolonged administration of a lyophilized-aqueous extract of red cabbage (250 and 500 mg/kg body weight) significantly blunted the imbalances in lipids, liver enzymes and renal osmolytes induced by the CRD. The effects of red cabbage were compared to simvastatin (30 mg/kg body weight) treated rats. Estimation of malondialdehyde and non-protein sulfhydryls revealed robust antioxidant properties of red cabbage. Histopathological analysis of livers from rats administered with red cabbage showed marked inhibition in inflammatory and necrotic changes triggered by CRD. Similarly, in vitro studies using a 2′,7′-Dichlorofluorescein-based assay showed that red cabbage conferred cytoprotective effects in cultured HepG2 cells. In conclusion, the present study discloses the potential therapeutic effects of red cabbage in dyslipidemia as well as hepatic injury, that is at least, partly mediated by its antioxidant properties.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Kokou Atchou ◽  
Povi Lawson-Evi ◽  
Aboudoulatif Diallo ◽  
Kwashie Eklu-Gadegbeku

Abstract Background Amaranthus spinosus is a medicinal plant used in traditional medicine to treat several diseases including diabetes and its complications. The aim of this study was to prove the safety of the plant in animal health. Methods The dry extract was obtained following the hydroethanolic extraction of A. spinosus roots. The cytotoxicity was evaluated in vitro by incubating Artemia salina larvae with the extract for 24 h. In vivo toxicity was assessed in Sprague Dawley rats. A single dose of 5000 mg/kg bw of extract was administered orally to female rats in acute toxicity and observed for 14 days for mortality and signs of toxicity. In subchronic toxicity, extract doses of 500 and 1000 mg/kg bw were administered orally to male and female rats for 28 consecutive days and observed for previous signs. Body weight was recorded daily and blood glucose levels every week. On day 29, blood was collected for biochemical and hematological studies. Organs were then exised for gross autopsy and histopathological examination. Results The in vitro study showed that the extract had a LC50 = 1.178 mg/mL in larvae and was considered to be non-cytotoxic. Oral administration of extract at a single dose of 5000 mg/kg bw did not cause any mortality or sign of toxicity in gross necropsy. In subchronic oral toxicity, repeated doses of 500 and 1000 mg/kg bw of extract, did not also cause any mortality or significant change in body weight, relative weight of vital organs. Furthermore, hematological and biochemical parameters and histopathological examination did not show any significant change. The observed decrease in blood glucose levels did not correlate with organ damage and supports the safety of the plant. However, the reduction of LDL-cholesterol has shown that the extract can prevent cardiovascular disease. Conclusions This finding demonstrated that A. spinosus root is non-toxic with a LD50 > 5000 mg/kg bw. Thus, the extract can be used for cutaneous and subchronic oral administration at doses ≤ 1000 mg/kg bw. However, further studies such as embryo/fetotoxicity, genotoxicity and neurotoxicity will be needed to prove the safety of chronic administration of the extract in patients and fetuses.


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