Liver Kidney Toxicity Research Articles

Antiobesity and antidiabetes effects of Cyperus rotundus rhizomes presenting protein tyrosine phosphatase, dipeptidyl peptidase 4, metabolic enzymes, stress oxidant and inflammation inhibitory potential

Diabetes is a significant global health concern that increases the vulnerability to various chronic illnesses. In view of this issue, the current research aimed to examine the effects of administering an extract derived from the tubers of Cyperus rotundus L (CrE) on obesity, type 1 diabetes, and liver-kidney toxicity. Through the utilization of HPLC-DAD analysis, it was discovered that the extract contained several components, including quercetin (47.8%), luteolin glucoside (17%), luteolin (7.56%), apigenin-7-glucoside (6.29%), naringinin (4.52%), and seven others. In vitro experiments they have demonstrated that CrE effectively inhibited key digestive enzymes associated with obesity and type 2 diabetes, such as DPP-4, PTP1B, lipase, and α-amylase, as evidenced by their respective IC50 values are about 23, 51,83, and 67 μg/ml respectively. Furthermore, when diabetic rats were administered CrE, the activity of pancreatic enzymes linked to inflammation, namely 5-lipoxygenase (5-LO), hyaluronidase (HAase), and myeloperoxidase (MPO), was significantly suppressed by 48, 41, 75, and 47%, respectively. Moreover, CrE exhibited protective effects on pancreatic β-cells by inhibiting the formation of thiobarbituric acid reactive substances (TBARS) by 65% and the induction of superoxide Dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities by 62, 108, and 112% respectively as compared to diabetic untreated rat. Additionally, CrE significantly inhibited the activities of intestinal, pancreatic, and serum lipase and α-amylase activities. In diabetic rats, CrE administration suppressed glycogen phosphorylase (GP) stimulated glycogen synthase (GS) activities by 45 and 30%; and this increased liver glycogen content by 45%. Furthermore, CrE modulated key hepatic enzymes involved in carbohydrate metabolism, including hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase (G6P), and fructose-1,6-bisphosphatase (FBP). Notably, the average food and water intake (AFI and AWI) of diabetic rats treated with CrE was reduced by 15 and 16% respectively as compared to those without any treatment. Therefore, this study demonstrated the effectiveness of Cyperus rotundus tubers in preventing and treating obesity and diabetes.

Protective effect of ethanolic extract of Elettaria Cardamomum against gentamicin hepato-renal toxicity in male albino rats.

Cardamom is one of the spices containing a wide range of antioxidants and is used in medicinal preparations. Thus, in this study, we want to explore the protective effect of ethanolic cardamom extract on the liver-kidney toxicity caused by gentamicin in male albino rats. The experiment was applied to twenty-eight male albino rats divided randomly into four groups. The control group was given 1 ml/kg of saline orally. The gentamicin (GM) group was given a daily 80 mg/kg i.p of GM for seven days. Another group was given 100 or 200 mg/kg b.wt. p.o. ethanolic extract of Elettaria Cardamomum (EC) for seven days. Blood and liver-kidney samples were taken after the end of the study for analyses to test for liver-kidney function and lipid profile (LP). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin activities were higher in the GM group than in the control group. However, the groups' differences in globulin levels and total protein (TP) were not statistically significant. Compared to the control group, the albumin level in the gentamicin group was considerably lower. On the other hand, creatinine and urea levels, lipid, serum total cholesterol levels, and high-density lipoprotein (HDL) significantly increased in the gentamicin group but decreased in the control group and co-treated groups with gentamicin and ethanolic extract EC. Low-density lipoprotein (LDL) significantly dropped, while the control group showed high levels of lipid and serum total cholesterol. EC ethanolic extract shields the liver-kidney against GM harmful effects in male rats. Recent research demonstrated that the effects of the plant cardamom were the same at both low-high doses. The phenolic elements in EC may be responsible for this protective effect.

Apigenin alleviates methotrexate-induced liver and kidney injury in mice.

Methotrexate (MTX) is a drug used in the treatment of various types of cancer and inflammatory diseases, but its clinical use has been restricted due to its toxicity. Apigenin (API) is an effective flavonoid with antioxidant and anti-inflammatory properties. The aim of this study was to determine the protective effect of API against MTX-induced liver and kidney toxicity. Four groups with 12 male mice each were used. The control and API groups were received 0.9% saline (ip) and API (3 mg/kg ip) for 4 days, respectively. The MTX group were given a single dose of MTX (20 mg/kg ip) on the fourth day. The MTX + API group were administered API for 7 days and then MTX on fourth day. Blood, liver and kidney were collected to evaluate tissue injury markers, oxidative stress biomarkers, and histopathological and immunohistochemical assessments. In MTX-treated group, significant increases in aminotransferases activities, creatinine and malondialdehyde (MDA) levels and significant decreases in catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase1 (SOD1) activities and glutathione (GSH) levels were determined compared to the control group. Furthermore, histopathological changes and significant increases in caspase-3, C-reactive protein (CRP), granulocyte colony-stimulating factor (G-CSF), and inducible nitric oxide synthase (iNOS) expressions were detected in both liver and kidney tissues of MTX-treated mice. Pretreatment with API alleviates liver and kidney toxicity by attenuating oxidative stress and tissue injury markers, histopathological alterations, and apoptosis and inflammation. These results suggest that API has a protective effect against oxidative stress and liver-kidney toxicity induced by MTX.

Fermented soy milk prepared using kefir grains prevents and ameliorates obesity, type 2 diabetes, hyperlipidemia and Liver-Kidney toxicities in HFFD-rats

Abstract In vitro, this study showed that unfermented soy milk (USM) and kefir fermented soy milk (FSM) inhibited pancreas lipase with (IC50 = 52.17 and 39.37 μg/mL) and α-amylase activities with (IC50 = 72.60 and 52.71 μg/mL respectively). The most powerful lipase and α -amylase inhibitory activity was observed around 16 h of fermentation. In HFFD rats, the supplement of FSM increased locomotor performance; and decreased intestinal and pancreas lipase activity by 34 and 35% as compared to untreated HDF-rats. This leads to decrease in TC and LDL-c by 24 and 66%; and increase in HDL-c rates of HFFD-rats by 32%, which helped to decrease in body weight by 20%. Moreover administration of FSM to HFFD-rats inhibited intestinal and pancreas α-amylase activity by 26 and 31% as compared to untreated HFFD-rats, and consequently decrease of blood glucose by 36%. In addition, FSM efficiently was protected from hepatic and kidney tissues toxicities.

Safety evaluation and risk control measures for Aconiti Kusnezoffii Radix

Through the comprehensive and systematic research of domestic and overseas literature and information, we studied ancient original records on Aconiti Kusnezoffii Radix and its toxicity, analyzed related adverse cases and the animal toxicity experiments in recent years, then systematically analyzed the safety of Aconitum and its preparations, and finally we summarized the clinical characteristics and potential risk factors related to the safety of Aconitum. A report on adverse events of Aconitum in 76 patients with myocardial damage and renal damage accounting for 53.9% and 42.1% respectively, indicated that the safety problems of Aconitum may be related to heart toxicity and liver-kidney toxicity. Aconitum had complex compositions, and based on the animal experiments, Aconitum decoction had the highest toxicity at 2 h, and it reduced significantly at 4 h, which showed that the toxic components mainly depend on the hydrolysis or the decomposition degree of diester diterpenoid alkaloids. According to the toxicity study, Aconitum toxicity might occur in cardiovascular system, nervous system, kidney, embryo, reproductive system, and it was contraindicated in pregnant women. So far, specific antidote for aconitine poisoning is still a blank. The key for treatment is to correct arrhythmia timely and effectively, maintain stable vital signs, and meanwhile, give gastric lavage, intravenous fluid infusion and other therapies. So we suggest that the basic study for Aconitum toxicology should be strengthened, and the pharmacology and mechanism of toxicity, as well as the mechanism of processing for raising efficiency and reducing toxicity, should be further clarified to determine the quantity-effect relationship and eliminate safety hazards in using Aconitum.

Phytoestrogens inhibit key-enzymes linked to obesity, type 2 diabetes and liver-kidney toxicity in high fructose-fat diet in mice

Objective: To evaluate the effect of the administration of phytoestrogens on obesity, type 2 diabetes, and liver-kidney toxicity.Methods: Phytoestrogens (phyto(E2)) were administrated to high fructose-fat diet (HFFD).Results: This study showed that administration of phyto(E2) to HFFD-mice inhibited lipase activity by 34%, decreased body weight by 20% and modulated lipid profile, showed a decrease in total-cholesterol (TC) and LDL-cholesterol (LDL-C) rates in the plasma by 59% and 42%, respectively, and increased the HDL-cholesterol (HDL-C) level by 31%. In addition, the administration of phytoestrogens to HFFD-mice exerts an inhibitory effect on α-amylase activity and decreased glucose level by 28% and increase in liver glycogen level by 33%; and ameliorate oral glucose tolerance test.Conclusions: This study demonstrate that phyto(E2) has both a promising potential with regards to the inhibition of intestinal lipase and α-amylase activities, and a valuable hypoglycemic and hypolipidemic function.

Physico-chemical characterization and beneficial effects of seaweed sulfated polysaccharide against oxydatif and cellular damages caused by alloxan in diabetic rats

The aim of this work was to evaluate the chemical characterization of a sulfated polysaccharide isolated from Codium fragile alga (CFSP), using various assays such as FTIR, XRD, GC-MS and NMR spectroscopy including 1H, 13C, COSY, HSQC, HMBC and NOESY experiments as well as its inhibitory effects on α-amylase activity, liver-kidney toxicities and lipid profile disorders in alloxan-induced diabetic rats. Combined results showed that the CFSP is composed mainly by a galactopyranose and d-glucose, with these various bonds and these various functional groups. The antihyperglycaemic effect of this polysaccharide resulted in a significant decrease in blood glucose and intestinal amylase levels. It had the effect of significantly restoring the hepatic, pancreatic and renal antioxidant enzymes with a significant reduction in TBARS levels. The CFSP also acted at the tissue by moderating the appearance of lipid vacuoles at the hepatocytes and restoring the general histological organization of the kidneys and pancreas.

Inhibitory activities of Cystoseira crinita sulfated polysaccharide on key enzymes related to diabetes and hypertension: in vitro and animal study

The present study investigated the effect of the Cystoseira crinita sulfated polysaccharide (CCSP) on key enzymes activities related to diabetes in vitro and in diabetic rats. We found that CCSP inhibited pancreatic α-amylase with IC50 = 39.16 μg/ml and angiotensin I-converting enzyme (ACE) activity with IC50 = 58.35 μg/ml in vitro. In diabetic rats, the administration of CCSP reduced the activity of α-amylase in serum, pancreas, and intestine by 23%, 44.38%, and 45%, respectively as compared to untreated diabetic rats. Moreover, the administration of CCSP to surviving diabetic rats protects pancreas β cells from death and damage, which leads to insulin levels. The decrease in α-amylase and the increase in insulin level lead to a decrease in glucose rate by 56% as compared to untreated diabetic rats. The inhibitory action of α-amylase activity and hypoglycemic effect of CCSP were confirmed by oral glucose tolerance test (OGTT). In addition, the administration of CCSP to surviving diabetic rats normalizes lipid profile, stimulates antioxidant capacity, and prevents liver–kidney toxicities, evidenced by decrease in serum indices of liver and kidney toxicity and confirmed by histological analysis. The overall findings presented in this study demonstrate that the administration of CCSP to diabetic rats can make it a potentially strong candidate for industrial application as a pharmacological agent for the treatment of hyperglycemia, hyperlipidemia, and liver–kidney dysfunctions.

Inhibitory effects of Cymodocea nodosa sulphated polysaccharide on α-amylase activity, liver-kidney toxicities and lipid profile disorders in diabetic rats

This study aimed to evaluate for the first time the effects of Cymodocea nodosa sulphated polysaccharide (CNSP) on the α-amylase activity, hyperglycaemia, liver-kidney functions, and pancreatic architecture of alloxan-induced diabetic rats. Animals were allocated into four groups of seven rats each, the body weight and blood glucose levels were estimated periodically for 2 months of treatment by gastric gavages route. The CNSP effect was confirmed by biochemical procedures and histological study. The inhibition of α-amylase activity and protection of pancreatic β-cells induced a decrease in the blood glucose levels and regulated the lipid profile in the plasma of the treated diabetic rats, which helped to maintain the homeostasis of blood lipid. Moreover, CNSP administration induced a significant decrease in the levels of lipid peroxidation in the pancreas, liver and kidney of diabetic rats and protects their functions attested by a decrease in the levels of toxicity parameters in blood.

Protective effect of Ruta Chalepensis L. extract on oxidative stress and liver-kidney function induced by polymicrobial sepsis in rats

Sepsis, a systemic inflammatory disease developed after an infectious insult and remains the major cause of death in intensive care units. The aim of this study was to examine the protective effect of the ethanolic extract of Ruta chalepensis L. (ERC) against oxidative stress and liver-kidney functions in cecal and ligation puncture (CLP) rats. In vitro, the results showed that ERC rich in phenolic compounds possessed important antioxidant activity. In vivo, CLP-induced oxidative stress evidenced by the increase of the TBARS and decrease in the enzymatic antioxidants (SOD, CAT, GPX) in liver and kidney. Moreover, CLP induced liver-kidney toxicities showed by an increase in the ALT, AST, PAL, LDH, BUN and creatinine in the plasma. However, the administration of ERC to CLP-rats prevents all these disorders. Positive action of ERC was confirmed by histo-pathological examination. Therefore this study suggests that ERC could be a potential therapeutic agent for sepsis treatment.

The Pharmacology of Inhaled Anesthetics

Department of Anesthesiology, University of Utah School of Medicine, Salt Lake City, Utah. talmage.egan@hsc.utah.edu.The Pharmacology of Inhaled Anesthetics. By Edmond I Eger, II, M.D., James B. Eisenkraft, M.D., Richard B. Weiskopf, M.D., Baxter Healthcare Corporation, New Providence, New Jersey, 2003. ISBN: TXV1-035635. Pages: 327 and 2 DVDs. Price: Complimentary.Authored by a group of distinguished clinician scientists who are internationally recognized for their contributions to the topic, The Pharmacology of Inhaled Anesthetics is an effectively organized, copiously illustrated, well-written review of both the basic and clinical pharmacology of inhalation anesthetics. From a clinical perspective, perhaps the primary aim of the authors was to compare and contrast the newer inhaled anesthetics, sevoflurane and desflurane, with the older, more soluble ones. In the broader context of how this work fits within the collection of existing textbooks on inhaled anesthesia, it can be viewed as an up-to-date review, integrating recent discoveries with well-established knowledge.The structure of the book conforms to the traditional areas of investigation for inhaled anesthetics. The initial chapters are focused on basic issues including a history of inhaled anesthetics, physiochemistry, the concept of minimum alveolar concentration, mechanisms of drug action, and pharmacokinetics. Several chapters addressing pharmacodynamics are organized by organ system (e.g. , circulatory effects and pulmonary effects). Next are chapters devoted to metabolism and liver-kidney toxicity. The book finishes with very practically oriented chapters discussing inhaled anesthetic delivery systems and clinical applications, offering “how to do it” recipes.The textbook is accompanied by a number of educational enhancements that clearly increase the overall appeal of the entire package, particularly for residents in training. Each chapter has a list of specific learning objectives. At the end of the book there is a list of study questions intended for students preparing for certification examinations. The answers to these questions can be submitted for scoring and continuing medical education credit. The book is also complete with a DVD-based supplement that complements the text. The DVD is essentially a video seminar focused on the topic; it is organized with the same chapter headings as the book. Filmed in the setting of a small classroom with a group of trainees and author, Edmond I. Eger II, M.D., the DVD seminar is a comprehensive lecture series with standard computer-generated slides. A unique feature of the DVD seminar is the inclusion of “in operating room” video clips created to illustrate the scientific foundation of inhaled anesthesia at the point of clinical care.The greatest strength of the book is its authoritative authorship. As major contributors to this area of anesthesia clinical pharmacology, these authors have organized their thinking on the topic over decades and are experienced in conveying this knowledge. The book therefore represents an up-to-date review of the entire area. In part because it brings together detailed information that was previously only available in separate monographs focused on the individual agents, and also because it includes the latest discoveries in the field (e.g. , new information about locus and mechanism of action, among many others), the book can be considered a “one-stop shopping” source of information on inhalation anesthesia.A unique aspect of the book that probably deserves mention is the nontraditional publishing pathway. Inspection of the title page does not mention a publishing house or a Library of Congress catalogue number. The title cannot be found through a search of popular online booksellers that feature current books in print. Because the book and the accompanying DVD recently appeared in the mail boxes of all our residents in training, I have surmised that the book was probably produced as a collaborative educational effort between an industry sponsor and Dr. Eger and colleagues, although it is impossible to be sure by examining the book. A clear statement of support would easily address this confusion and would be appropriate in the spirit of conflict of interest disclosure. In any case, this reviewer believes that the authors have provided a balanced appraisal of the topic.All in all, I couldn’t be much more enthusiastic about this book, particularly for the resident in training audience. It’s well done. It’s authoritative. And, as best I can tell, it’s free.