scholarly journals Effect of Berberis vulgaris L. root extract on ifosfamide-induced in vivo toxicity and in vitro cytotoxicity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shazia Ilyas ◽  
Raheela Tabasum ◽  
Ali Iftikhar ◽  
Mamoona Nazir ◽  
Amina Hussain ◽  
...  
Keyword(s):  
Side Effects ◽  
Combination Therapy ◽  
Hela Cells ◽  
Complete Blood Count ◽  
Lipid Lowering ◽  
Albino Rats ◽  
Root Extract ◽  
Protective Effects ◽  
Berberis Vulgaris

AbstractIfosfamide is a widely used chemotherapeutic agent having broad-spectrum efficacy against several tumors. However, nephro, hepato, neuro cardio, and hematological toxicities associated with ifosfamide render its use limited. These side effects could range from organ failure to life-threatening situations. The present study aimed to evaluate the attenuating efficiency of Berberis vulgaris root extract (BvRE), a potent nephroprotective, hepatoprotective, and lipid-lowering agent, against ifosfamide-induced toxicities. The study design comprised eight groups of Swiss albino rats to assess different dose regimes of BvRE and ifosfamide. Biochemical analysis of serum (serum albumin, blood urea nitrogen, creatinine, alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, total cholesterol, and triglycerides) along with complete blood count was performed. Kidney, liver, brain, and heart tissue homogenates were used to find malondialdehyde, catalase, and glutathione S-transferase levels in addition to the acetylcholinesterase of brain tissue. The results were further validated with the help of the histopathology of the selected organs. HeLa cells were used to assess the effect of BvRE on ifosfamide cytotoxicity in MTT assay. The results revealed that pre- and post-treatment regimens of BvRE, as well as the combination therapy exhibited marked protective effects against ifosfamide-induced nephro, hepato, neuro, and cardiotoxicity. Moreover, ifosfamide depicted a synergistic in vitro cytotoxic effect on HeLa cells in the presence of BvRE. These results corroborate that the combination therapy of ifosfamide with BvRE in cancer treatment can potentiate the anticancer effects of ifosfamide along with the amelioration of its conspicuous side effects.

scholarly journals Quantification of Berberine in Berberis vulgaris L. Root Extract and Its Curative and Prophylactic Role in Cisplatin-Induced In Vivo Toxicity and In Vitro Cytotoxicity

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 185 ◽  
Author(s):  
Sarfraz Ahmad ◽  
Amina Hussain ◽  
Aroosha Hussain ◽  
Iskandar Abdullah ◽  
Muhammad Sajjad Ali ◽  
...  
Keyword(s):  
Hela Cells ◽  
In Vitro Cytotoxicity ◽  
Root Extract ◽  
Protective Agent ◽  
Protective Effects ◽  
Prophylactic Regimen ◽  
In Vivo Toxicity ◽  
Berberis Vulgaris

Cisplatin is amongst the most potent chemotherapeutic drugs with applications in more than 50% of cancer treatments, but dose-dependent side effects limit its usefulness. Berberis vulgaris L. (B. vulgaris) has a proven role in several therapeutic applications in the traditional medicinal system. High-performance liquid chromatography was used to quantify berberine, a potent alkaloid in the methanolic root extract of B. vulgaris (BvRE). Berberine chloride in BvRE was found to be 10.29% w/w. To assess the prophylactic and curative protective effects of BvRE on cisplatin-induced nephrotoxicity, hepatotoxicity, and hyperlipidemia, in vivo toxicity trials were carried out on 25 healthy male albino Wistar rats (130–180 g). Both prophylactic and curative trials included a single dose of cisplatin (4 mg/kg, i.p.) and nine doses of BvRE (500 mg/kg/day, orally). An array of marked toxicity effects appeared in response to cisplatin dosage evident by morphological condition, biochemical analysis of serum (urea, creatinine, total protein, alanine transaminase, aspartate transaminase, total cholesterol, and triglyceride), and organ tissue homogenates (malondialdehyde and catalase). Statistically-significant (p < 0.05) variations were observed in various parameters. Moreover, histological studies of liver and kidney tissues revealed that the protective effect of BvRE effectively minimized and reversed nephrotoxic, hepatotoxic, and hyperlipidemic effects caused by cisplatin in both prophylactic and curative groups with relatively promising ameliorative effects in the prophylactic regimen. The in vitro cell viability effect of cisplatin, BvRE, and their combination was determined on HeLa cells using the tetrazolium (MTT) assay. MTT clearly corroborated that HeLa cells appeared to be less sensitive to cisplatin and berberine individually, while the combination of both at the same concentrations resulted in growth inhibition of HeLa cells in a remarkable synergistic way. The present validated the use of BvRE as a protective agent in combination therapy with cisplatin.

Bitter Melon Protects Against Lipid Peroxidation Caused by Immobilization Stress in Albino Rats

2009 ◽  
Vol 79 (1) ◽  
pp. 48-56 ◽  
Author(s):  
Chaturvedi
Keyword(s):  
Lipid Peroxidation ◽  
Immobilization Stress ◽  
Reduced Glutathione ◽  
Cumene Hydroperoxide ◽  
Liver Homogenate ◽  
Thiobarbituric Acid ◽  
Albino Rats ◽  
Bitter Melon ◽  
Protective Effects

In the present study, protective effects of bitter melon (Momordica charantia) extract on lipid peroxidation induced by immobilization stress in rats have been assessed. Graded doses of extract (50, 100, and 150 mg/kg body weight) were administered orally to rats subjected to immobilization stress for two hours for seven consecutive days. Stress was applied by keeping the rats in a cage where no movement was possible. After seven days, rats were killed by decapitation after ether anesthesia. Blood and liver were collected to measure thiobarbituric acid reactive substances, reduced glutathione, and catalase. In vitro effects of M. charantia extract on lipid peroxidation in liver homogenate of normal, control, and rats pretreated with extract were carried out against cumene hydroperoxide-induced lipid peroxidation. Results reveal that in vivo M. charantia inhibited stress-induced lipid peroxidation by increasing the levels of reduced glutathione and activities of catalase. These results were further supported by in vitro results. In vitro inhibition of lipid peroxidation was indicated by low levels of thiobarbituric acid in the liver homogenate from pretreated rats and normal rats when incubated with both cumene hydroperoxide and extract. Inhibition was also noted in the homogenate where the rats were pretreated but the mixture contained no extract. Thus this plant provides protection by strengthening the antioxidants like reduced glutathione and catalase. Inclusion of this plant in the daily diet would be beneficial.

scholarly journals Probucol Attenuates Cyclophosphamide-induced Oxidative Apoptosis, p53 and Bax Signal Expression in Rat Cardiac Tissues

2010 ◽  
Vol 3 (5) ◽  
pp. 308-316 ◽  
Author(s):  
Yousif A. Asiri
Keyword(s):  
Superoxide Dismutase ◽  
Glutathione Peroxidase ◽  
Mrna Expression ◽  
Corn Oil ◽  
Lipid Lowering ◽  
Control Group ◽  
Albino Rats ◽  
Protective Effects ◽  
Antioxidant Genes ◽  
Cardiac Tissues

Cyclophosphamide (CP) is a widely used drug in cancer chemotherapy and immunosuppression, which could cause toxicity of the normal cells due to its toxic metabolites. Probucol, a cholesterol-lowering drug, acts as potential inhibitor of DNA damage and shows to protect against doxorubicin-induced cardiomyopathy by enhancing the endogenous antioxidant system including glutathione peroxidase, catalase and superoxide dismutase. This study examined the possible protective effects of probucol, a lipid-lowering compound with strong antioxidant properties, against CPinduced cardiotoxicity. This objective could be achieved through studying the gene expression-based on the possible protective effects of probucol against CP-induced cardiac failure in rats. Adult male Wistar albino rats were assigned into four treatment groups: Animals in the first (control) and second (probucol) groups were injected intraperitoneally with corn oil and probucol (61 mg/kg/day), respectively, for two weeks. Animals in the third (CP) and fourth (probucol plus CP) groups were injected with the same doses of corn oil and probucol (61 mg/kg/day), respectively, for one week before and one week after a single dose of CP (200 mg/kg, I.P.). The p53, Bax, Bcl2 and oxidative genes signal expression were measured by real time PCR. CP-induced cardiotoxicity was clearly observed by a significant increase in serum creatine phosphokinase isoenzyme (CK-MB) (117%), lactate dehydrogenase (LDH) (64%), free (69%) and esterified cholesterol (42%) and triglyceride (69%) compared to control group. In cardiac tissues, CP significantly increases the mRNA expression levels of apoptotic genes, p53 with two-fold and Bax with 1.6-fold, and decreases the anti-apoptotic gene Bcl2 with 0.5-fold. Moreover, CP caused downregulation of antioxidant genes, glutathione peroxidase, catalase, and superoxide dismutase and increased the lipid peroxidation and decreased adenosine triphosphate (ATP) (40%) and ATP/ADP (44%) in cardiac tissues. Probucol pretreatment not only counteracted significantly the CP-induced increase in cardiac enzymes and apoptosis but also induced a significant increase in mRNA expression of antioxidant enzymes and improved ATP, ATP/ADP, glutathione (GSH) in cardiac tissues. In conclusion, data from the present study suggest that probucol prevents the development of CP-induced cardiotoxicity by a mechanism related, at least in part, to its ability to increase mRNA expression of antioxidant genes and to decrease apoptosis in cardiac tissues with the consequent improvement in mitochondrial oxidative phosphorylation and energy production.

scholarly journals Antiartherosclerotic Effects of Plant Flavonoids

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Shamala Salvamani ◽  
Baskaran Gunasekaran ◽  
Noor Azmi Shaharuddin ◽  
Siti Aqlima Ahmad ◽  
Mohd Yunus Shukor
Keyword(s):  
Cardiovascular Diseases ◽  
Side Effects ◽  
Animal Models ◽  
Vascular Diseases ◽  
Lipid Lowering ◽  
Peripheral Vascular ◽  
Heart Attacks ◽  
Synthetic Drug

Atherosclerosis is the process of hardening and narrowing the arteries. Atherosclerosis is generally associated with cardiovascular diseases such as strokes, heart attacks, and peripheral vascular diseases. Since the usage of the synthetic drug, statins, leads to various side effects, the plants flavonoids with antiartherosclerotic activity gained much attention and were proven to reduce the risk of atherosclerosisin vitroandin vivobased on different animal models. The flavonoids compounds also exhibit lipid lowering effects and anti-inflammatory and antiatherogenic properties. The future development of flavonoids-based drugs is believed to provide significant effects on atherosclerosis and its related diseases. This paper discusses the antiatherosclerotic effects of selected plant flavonoids such as quercetin, kaempferol, myricetin, rutin, naringenin, catechin, fisetin, and gossypetin.

scholarly journals Lipid Lowering Activity ofAnthocephalus indicusRoot in Hyperlipidemic Rats

2010 ◽  
Vol 7 (3) ◽  
pp. 317-322 ◽  
Author(s):  
Vishnu Kumar ◽  
Mohammad Mubin Khan ◽  
Ashok Kumar Khanna ◽  
Ranjana Singh ◽  
Sushma Singh ◽  
...  
Keyword(s):  
Hydroxyl Radicals ◽  
Plasma Lipids ◽  
Antioxidant Activities ◽  
Lipolytic Activity ◽  
Lipid Lowering ◽  
Root Extract ◽  
Superoxide Anions ◽  
Post Heparin Lipolytic Activity ◽  
Lowering Activity

The lipid lowering activity ofAnthocephalus indicus(family Rubiaceae; Hindi name Kadamba) root extract has been studied in triton WR-1339 induced hyperlipidemia in rats. In this model, feeding with root extract (500 mg kg−1b.w.) lowered plasma lipids and reactivated post-heparin lipolytic activity in hyperlipidemic rats. Furthermore, the root extract (50–500 μM) inhibited the generation of superoxide anions and hydroxyl radicals, in both enzymic and non-enzymic systems,in vitro. The results of the present study demonstrated both lipid lowering and antioxidant activities in root extract ofA. indicus, which could help prevention of hyperlipidemia and related diseases.

scholarly journals Curcumin: Phytochemical Therapy in the Treatment of Hyperlipidemia

2019 ◽  
Keyword(s):  
Side Effects ◽  
Curcuma Longa ◽  
Experimental Studies ◽  
Lipid Lowering ◽  
Modern World ◽  
Therapeutic Effects ◽  
Synthetic Drugs ◽  
Wide Range

In modern world, hyperlipidemia is the most common disorder mainly caused by lifestyle habits and the major cause of cardiovascular, coronary and atherosclerotic changes. Such disorder is characterized by abnormally elevated levels of any or all lipids or lipoproteins in the blood. A wide range of drugs are available for the treatment of hyperlipidemia, class of antihyperlipidemic drugs, but such drug-therapies are carried out with presence of various side effects. In the last decades, different in vitro and in vivo research have been conducted to confirm the therapeutic effects of various phytochemical agents that overcome the side effects caused by synthetic drugs. According to Ayurvedic recommendations and experimental studies, numerous phytochemical agents have been reported to possess different antihyperlipidemic properties. One of the most studied phytochemical agent - curcumin, herbal polyphenol and active ingredient which can be extracted from the powder rhizome of the plant Curcuma longa, has been reported to possess a wide range of pharmacological properties such as antimicrobial, antioxidative, antiinflammatory and anticancer property. Recent studies also suggests curcumin as potential lipid lowering candidate in treatment of hyperlipidemia. The aim of this review is to present and discuss phytochemistry, molecular mechanism of hypolipidemic activity of curcumin, demonstrating its importance as potential therapy for the treatment of hyperlipidemia.

scholarly journals Protective Effects of Rhodiola Crenulata Extract on Hypoxia-Induced Endothelial Damage via Regulation of AMPK and ERK Pathways

2018 ◽  
Vol 19 (8) ◽  
pp. 2286 ◽  
Author(s):  
Pi-Kai Chang ◽  
I-Chuan Yen ◽  
Wei-Cheng Tsai ◽  
Tsu-Chung Chang ◽  
Shih-Yu Lee
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Umbilical Vein ◽  
Hypoxic Exposure ◽  
No Production ◽  
Root Extract ◽  
Protective Effects ◽  
Rhodiola Crenulata

Rhodiola crenulata root extract (RCE) has been shown to possess protective activities against hypoxia both in vitro and in vivo. However, the effects of RCE on response to hypoxia in the endothelium remain unclear. In this study, we aimed to examine the effects of RCE in endothelial cells challenged with hypoxic exposure and to elucidate the underlying mechanisms. Human umbilical vein endothelial cells were pretreated with or without RCE and then exposed to hypoxia (1% O2) for 24 h. Cell viability, nitric oxide (NO) production, oxidative stress markers, as well as mechanistic readouts were studied. We found that hypoxia-induced cell death, impaired NO production, and oxidative stress. These responses were significantly attenuated by RCE treatment and were associated with the activation of AMP-activated kinase and extracellular signal-regulated kinase 1/2 signaling pathways. In summary, we showed that RCE protected endothelial cells from hypoxic insult and suggested that R. crenulata might be useful for the prevention of hypoxia-associated vascular dysfunction.

Tiopronin protects against the nephrotoxicity of cisplatin in the rat

1999 ◽  
Vol 18 (12) ◽  
pp. 713-717 ◽  
Author(s):  
J-G Zhang ◽  
M Viale ◽  
M Esposito ◽  
W E Lindup
Keyword(s):  
Body Weight ◽  
Antitumour Activity ◽  
Rat Kidney ◽  
The Body ◽  
Albino Rats ◽  
Protective Effects ◽  
Kidney Weight ◽  
Plasma Urea ◽  
Cisplatin Nephrotoxicity

1 Tiopronim (N-(2-mercaptopropionyl)-glycine) is a drug with a free thiol (sulphydryl) group that is used clinically. We have reported previously that tiopronin protects rat kidney slices in vitro from the nephrotoxic effects of cisplatin and does not reduce the antitumour activity of cisplatin. Tiopronin has been investigated therefore for its protective effects in rats in vivo. 2 The extent of kidney damage was studied 5 days after the administration of cisplatin. A single injection (i.p.) of cisplatin (6 mg/kg; 20,umollkg) to female Wistar albino rats caused a sustained decrease in body weight and, after 5 days, plasma urea, creatinine and kidney weight were increased. Tiopronin (2.5 mmol/kg, p.o.) ameliorated cisplatin nephrotoxicity when given 1 h before cisplatin. Tiopronin provided marked protection against cisplatin-induced increases in urea (from 237+19 mg to 48+23 mg/100 ml; control: 17+1) and creatinine (from 6.5+0.5 to 1.7+0.5 mg/100 ml control: 1.0 + 0.1). Tiopronin did not, prevent the body weight loss caused by cisplatin. In addition, an intraperitoneal dose (1 mmol/lkg) oftiopronin afforded similar protection to that of an oral dose. Rats that received an i.p. mixture of cisplatin (6 mg/kg) and tiopronin (65 mg/kg) displayed generally less toxicity, as indicated by a small fall in body weight and smaller increases in urea and creatinine and kidney weight. 3 The results show that tiopronin protects against cisplatin-induced nephrotoxicity. Oral administration of tiopronin may be a clinically useful way to prevent cisplatin nephrotoxicity.

scholarly journals Naringin alleviates methotrexate-induced liver injury in male albino rats and enhances its antitumor efficacy in HepG2 cells

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Hany Elsawy ◽  
Abdulmohsen I. Algefare ◽  
Manal Alfwuaires ◽  
Mahmoud Khalil ◽  
Omar M. Elmenshawy ◽  
...  
Keyword(s):  
Protein Expression ◽  
Hepg2 Cells ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Albino Rats ◽  
Dependent Manner ◽  
Protective Effects ◽  
Expression Ratio ◽  
Hepatocyte Ultrastructure

Abstract Methotrexate (MTX) is an efficient chemotherapeutic and immunosuppressant drug, but the hepatotoxicity of MTX limits its clinical use. Naringin (Nar) is a flavonoid derived from Citrus paradise, and has been shown to possess several pharmacological activities, including free-radical scavenging and antioxidant properties. In the present study, we first tested the possible protective effects of multiple doses of Nar against MTX-induced acute hepatotoxicity in rats, and then we investigated the growth inhibition and apoptotic effects of MTX and/or Nar against the HepG2 hepatocarcinoma cell line. Our in vivo results showed that Nar significantly reduced MTX-induced increases in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin levels. Nar also reduced MTX-induced oxidative stress by significantly reducing liver malondialdehyde (MDA) and nitric oxide (NO) content and increasing superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH). In addition, Nar significantly counteracted MTX-induced increases in hepatic interleukin-6 and tumor necrosis factor-α (TNF-α). Further, Nar greatly protected hepatocyte ultrastructure against MTX-induced injury. In contrast, in vitro MTX and/or Nar treatment of HepG2 cells for 48 h exhibited a cytotoxic effect and induced apoptosis in a dose-dependent manner mediated by a significant increase in the Bax/Bcl-2 protein expression ratio. Noticeably, Nar potentiated the MTX effect on the Bax/Bcl-2 ratio. In conclusion, Nar decreased MTX-induced functional and ultrastructural liver damage in a tumor-free animal model. Also, our data introduce MTX and Nar as promising antiproliferative agents with a distinctive mode of action, inducing apoptosis in HepG2 tumor cells through activation of Bax and down-regulation of Bcl-2 protein expression.

scholarly journals Synergistic Effect of β-Carotene and Metformin on Antihyperglycemic and Antidyslipidemic Activities in Streptozotocin-Induced Diabetic Rats

2021 ◽  
pp. 79-87
Author(s):  
Khadiza Khanam ◽  
Sultana Rajia ◽  
Mim Yeasmin ◽  
Munira Morshed ◽  
Rashidul Haque
Keyword(s):  
Combination Therapy ◽  
Low Density Lipoprotein ◽  
Fasting Blood Glucose ◽  
Density Lipoprotein ◽  
Diabetic Control ◽  
Biological Properties ◽  
Albino Rats ◽  
Protective Effects ◽  
Antidiabetic Therapy ◽  
Β Carotene

Purpose: Worldwide prevalence of diabetes mellitus (DM) has become an issue of great concern in current decades. To date, a large number of biological properties have been reported from carotenoids, particularly protective effects against cancer, cardiovascular diseases, and DM, including enhancement of insulin sensitivity.In this study, we aimed to evaluate the efficacy of β-carotene as an additive agent with metformin in ameliorating Type2 (T2)DM. Methods: In this experiment, fasting blood glucose level (BGL), low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol (TC) and triglycerides (TG) were measured in serum of Wister albino rats with streptozotocin (STZ)-induced diabetes and after treatment with metformin (850mg/70kg b.w.) and β-carotene (10 mg/70kg b.w.) administered orally once daily for three weeks. Results: Metformin and β-carotene treatments individually resulted in significant (p<0.001) reversal of the diabetes induced increase in BGL, LDL, TC and TG, whereas significantly increased the STZ-induced decrease in HDL, compared to diabetic control. As compared to the monotherapy, the combination therapy with metformin and β-carotene showed a significant (p<0.001) attenuation of BGL and serum level of LDL, TC, and TG and a slight increase (p<0.05) in serum HDL level, as compared to the treatment with β-carotene, but not with metformin. Conclusion: The combination therapy of β-carotene and metformin produced a significant antidiabetic and antihyperlipidemic effect than the monotherapy alone and provides a scientific rationale for their use in antidiabetic therapy as a potential antioxidant.

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