scholarly journals Hepatoprotective Activity of Hedyotis corymbosa (Linn.) Lam. Extract Against Anti-Tubercular Drug Induced Hepatic Damage in Sprague-Dawley Rats

2018 ◽  
Vol 21 (2) ◽  
pp. 131-138
Author(s):  
Shah Marzia Mahjabin Lina ◽  
Imran Ashab ◽  
M Salahuddin Bhuiya ◽  
Masum Shahriar

The aim of this study was to investigate the protective actions of hydroalcoholic extract of Hedyotis corymbosa against hepatotoxicity caused by different combinations of anti-tubercular drugs. Antitubercular drugs isoniazid and rifampicin were used to make the elevated level of ALT, AST, ALP and bilirubin as well as decreased level of albumin and total protein. Hepatoprotective activity of the plant was indicated when it causes the decrease of these marker enzymes and elevated level of albumin and total protein. H. corymbosa prevented liver damage caused by anti-tubercular drugs and also from histopathological changes. It can be concluded from the above experiment that hydroalcoholic extract of H. corymbosa showed significant hepatoprotective activity against antitubercular drugs.Bangladesh Pharmaceutical Journal 21(2): 131-138, 2018

Author(s):  
F. G. Zaki ◽  
E. Detzi ◽  
C. H. Keysser

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.


2020 ◽  
Vol 19 (8) ◽  
pp. 1745-1752
Author(s):  
Heshu Sulaiman Rahman ◽  
Kashan Alaalddin Bayz ◽  
Ridha Hassan Hussein ◽  
Azad Ismael Abdalla ◽  
Hemn Hassan Othman ◽  
...  

Purpose: To determine the phenolic and flavonoid contents of R. sativus rhizome ethanol extract and the hepatoprotective effect of the extract in rats. Methods: Folin–Ciocalteau and aluminum chloride colorimetric tests were used to determine the contents of phenols and flavonoids in the R. sativus extract. Male Sprague-Dawley rats induced with CCl4 to develop hepatotoxicity were treated orally with R. sativus extract for 4 weeks. The  antioxidant and anti-inflammatory effects of the extract on the liver were determined by evaluating the concentration of oxidative analytes, serum liver enzymes and lipids, and hepatic histopathology and cytochrome P450 2E1 expression. Results: R. sativus extract significantly (p < 0.05) reduced the hepatotoxic effect of CCl4 via its antioxidant activities and protection of liver tissues from oxidative damage. Conclusion: The hepatoprotective effects of R. sativus rhizome ethanol extract are attributed to its highphenolic and flavonoid contents. Keywords: R. savitus rhizome, Phenols, Flavonoid contents, antioxidant, Hepatoprotective


MicroRNA ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 224-231
Author(s):  
Amin Derakhshanfar ◽  
Javad Moayedi ◽  
Mahjoob Vahedi ◽  
Abouzar Valizadeh

Background: Arum conophalloides (A. conophalloides) is a wild edible delicate plant, widely used in traditional medicine. Objective: This study aimed to examine the effects of A. conophalloides extracts on biochemical, molecular, and histopathological changes in the rat. Methods: Fifty adult male Sprague-Dawley rats were divided into 5 groups (10 each) as follows: G1 or control, received distilled water; G2 and G3, treated with the aqueous extract at doses of 200 and 400 mg/kg; G4 and G5, treated with the hydroalcoholic extract at doses of 200 and 400 mg/kg. Prior to and at the end of the experiments, the serum levels of biochemistry parameters and the relative expression of miR-122 were assessed. Moreover, the liver and kidney tissues were examined microscopically. Results: Liver and kidney tissues showed normal structure in all groups. There were no significant changes in biochemical indices or the expression of miR-122 in the extract-treated groups at the dose of 200 mg/kg. However, the group that received the aqueous extract at the dose of 400 mg/kg exhibited a significantly lower level of HDL, LDL, ALT, and ALP in comparison to the control. Additionally, miR-122 expression in this group exhibited a 10-fold increase (P=0.009). Conclusion: The serum level of hepatocyte-specific miR-122 will be more helpful in detecting hepatic changes in early stages than ALT and AST activity or histopathological evaluations of liver sections. Our findings highlight the potential hepatotoxicity of A. conophalloides aqueous extract in a rat model.


2016 ◽  
Vol 45 (2) ◽  
pp. 344-352 ◽  
Author(s):  
Michael E. Dunn ◽  
Thomas G. Manfredi ◽  
Kevin Agostinucci ◽  
Steven K. Engle ◽  
Josh Powe ◽  
...  

Given the proven utility of natriuretic peptides as serum biomarkers of cardiovascular maladaptation and dysfunction in humans and the high cross-species sequence conservation of atrial natriuretic peptides, natriuretic peptides have the potential to serve as translational biomarkers for the identification of cardiotoxic compounds during multiple phases of drug development. This work evaluated and compared the response of N-terminal proatrial natriuretic peptide (NT-proANP) and N-terminal probrain natriuretic peptide (NT-proBNP) in rats during exercise-induced and drug-induced increases in cardiac mass after chronic swimming or daily oral dosing with a peroxisome proliferator-activated receptor γ agonist. Male Sprague-Dawley rats aged 8 to 10 weeks were assigned to control, active control, swimming, or drug-induced cardiac hypertrophy groups. While the relative heart weights from both the swimming and drug-induced cardiac hypertrophy groups were increased 15% after 28 days of dosing, the serum NT-proANP and NT-proBNP values were only increased in association with cardiac hypertrophy caused by compound administration. Serum natriuretic peptide concentrations did not change in response to adaptive physiologic cardiac hypertrophy induced by a 28-day swimming protocol. These data support the use of natriuretic peptides as fluid biomarkers for the distinction between physiological and drug-induced cardiac hypertrophy.


2021 ◽  
Author(s):  
Sameera Khurshid ◽  
Zaid Abdul Razzak ◽  
Shabana Usman Simjee

Abstract Brain derived neurotropic factors (BDNF) can be secreted either as a pro-BDNF or a mature form (mBDNF) through γ-amino-butyric acid (GABAA) receptors activation. Depolarization of GABA neurons in spinal cord can be mediated through N-methyl-D-aspartate (NMDA) receptor due to the exogenous secretion of over expressed BDNF. This over expressed BDNF further modulate the excitation and sensitization of nociceptors. We investigated the modulation of BDNF by GABAA agonist i.e., gabapentin, indomethacin (non-steroidal anti-inflammatory) and their low-dose combination on adjuvant-induced inflammatory arthritis. Mycobacterium tuberculosis H37Ra strain, as adjuvant, was injected in the tail base of female Sprague-Dawley rats. Gabapentin (5 mg/kg), indomethacin (5 mg/kg) and low dose combination of gabapentin (1.5 mg/kg) + indomethacin (2.5 mg/kg) were used. Paw edema was measure by plethysmometer and chronic pain was measured by plantar apparatus. Nitric oxide, peroxide and superoxide dismutase levels were also measured to analyze the free radical and antioxidant balance in different treatment groups along with the total protein concentration. Significant reduction of nitric oxide, peroxide as well as total protein concentration was found in low dose combination. Immunohistochemistry data also showed that the low dose combination has more potential in lowering the BDNF expression in cortex as well as in hippocampus region of brain as compared to their mono therapies. Our study suggested that low-dose combination of gabapentin and indomethacin has a significant impact on lowering the chronic and its associated markers as compare to their monotherapy. Thus indicated the additive effects of the combination therapy on neuropathic pain.


2020 ◽  
Vol 34 (11) ◽  
pp. 1316-1325
Author(s):  
Ahmad A Altarifi ◽  
Megan J Moerke ◽  
Mohammad I Alsalem ◽  
S Stevens Negus

Background: Tramadol is a widely used analgesic that activates mu-opioid receptors (MOR) and inhibits serotonin and norepinephrine transporters. This mixed pharmacology may limit both its own abuse potential and its modulation of abuse potential of other MOR agonists. Aims: This study used an intracranial self-stimulation (ICSS) procedure to compare abuse-related effects produced by acute or repeated treatment with tramadol or morphine in rats. Abuse potential in ICSS procedures is indicated by a drug-induced increase (or ‘facilitation’) of ICSS responding. Methods: Adult male Sprague–Dawley rats were implanted with electrodes targeting the medial forebrain bundle and trained to respond on a lever for pulses of electrical brain stimulation. Tramadol effects were evaluated after acute administration (3.2–32 mg/kg) in the absence or presence of the opioid antagonist naltrexone, the CYP2D6 hepatic-enzyme inhibitor quinine or a combination of both. Additionally, both tramadol and morphine were also tested before and after repeated tramadol (32 mg/kg/day for six days) or repeated morphine (3.2 mg/kg/day for six days). Results: Acute tramadol produced primarily ICSS rate-decreasing effects that were antagonised by naltrexone but not by quinine or naltrexone + quinine. Tramadol also produced little or no ICSS facilitation after repeated tramadol or repeated morphine, and repeated tramadol did not enhance ICSS facilitation by morphine. By contrast, morphine-induced ICSS facilitation was enhanced by repeated morphine treatment. Conclusions: These results suggest that tramadol has lower abuse potential than other abused MOR agonists and that repeated tramadol exposure produces relatively little enhancement of abuse potential of other MOR agonists.


Author(s):  
Rehana Parveen ◽  
Abdul Wadud ◽  
Shariq Shamsi ◽  
Shaista Parveen

Abstract Objectives Parshioshan (Adiantum capillus-veneris L.), Duqu (Peucedanum grande C.B. Clarke), Kaknaj (Physalis alkekengi L.) and Kharekhasak (Tribulus terresteris L.) have been selected for this study as they have been associated with medicinal actions for litholytic activity. Methods The experiment was carried out in Sprague Dawley rats divided into seven groups, serving as plain control, disease control, standard control, curative A and B and preventive A and B groups. Animals of plain control received distilled water. Remaining six groups received Ethylene glycol 0.75% and Ammonium chloride 1% by adding in the drinking water for the first three days followed by 0.75% Ethylene glycol for 18 days. From 8th day till 21st day, standard control received Cystone in the dose of 750 mg/kg. Preventive and curative test groups were treated with hydroalcoholic extract of the test drug in the dose of 132 mg/kg and 264 mg/kg from 1st to 21st day and 8th to 21st day of calculi induction. Results Test drug reduced the number of calcium oxalate crystals in the urine; the level of urinary calcium, creatinine, magnesium, phosphorus, sodium and chloride decreased significantly in standard and test groups. The urine volume increased significantly in all the test groups. The level of serum calcium, urea, phosphorus and creatinine were significantly reduced in all the test groups. Conclusions These results indicated that the test drug reduced and prevented the growth of urinary stones. Moreover, the test drug also possessed significant antiurolithiatic activity. However, the protective effect was found more than its curative effect.


2018 ◽  
Vol 30 (1) ◽  
pp. 131-137 ◽  
Author(s):  
Shaikh Zohra Meena ◽  
Md. Azizur Rahman ◽  
Paramdeep Bagga ◽  
Md. Mujahid

Abstract Background Development of drug-induced hepatic damage (DIHD) during chemotherapy is the most common reason for interruption in chemotherapy. This study evaluated the hepatoprotective activity of the ethanolic extract of Tamarindus indica stem bark (EETI) against the induced DIHD in Sprague Dawley rats. Methods The rats were divided into five groups (n=5). Group I, group III, group IV, and group V rats received 1 mL 1% carboxymethyl cellulose, EETI 100 mg/kg body weight (b.wt), EETI 200 mg/kg b.wt, and silymarin 100 mg/kg b.wt, respectively, orally once every day for 28 days. After 1 h–group II, group III, group IV, and group V rats were administered with isoniazid (INH) and rifampicin (RIF) 50 mg/kg b.wt each orally once every day for 28 days. Then, 24 h after the last dosing, blood was withdrawn from the rats and analyzed for liver specific enzymes and biochemical markers. They were examined for histopathology. Results Co-administration of INH and RIF in group II significantly increased alanine transaminase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, serum bilirubin, and cholesterol levels while reduced the total protein and albumin levels compared to that of group I. EETI in group III and group IV rats significantly restored the liver specific enzymes and biochemical markers altered due to co-administration of INH and RIF to normal in a dose-dependent manner. EETI 200 mg/kg b.wt showed better protection to liver than EETI 100 mg/kg b.wt and was comparable to silymarin 100 mg/kg b.wt. It was well supported with histopathology of liver tissues. Conclusions EETI possesses hepatoprotective activity against DIHD in rats. It may have a substantial impact on developing clinical strategies to treat patients with hepatic damage.


2014 ◽  
Vol 3 (5) ◽  
pp. 270-274 ◽  
Author(s):  
Maraia Farag Elmhdwi ◽  
Saleh Mosbah Muftah ◽  
Salem Gaber El tumi ◽  
Fatma Al-zaroug Elslimani

This study was designed to investigate the antioxidant and hepatoprotective activity of Ecballium elaterium "Fruit juice" extract against paracetamol induced hepatotoxicity in male albino rats. The hepatotoxicity was induced by acetaminophen (PCM) at dose of 400 mg/kg in male albino rats. It was administered orally once a day, every 48 h at the same time for twenty two days. The biochemical liver functional tests ALT, AST, ALP, total bilirubin, total protein, antioxidant enzymes (GR, GPx, CAT, SOD), and histopathological changes were examined. Our results showed that Levels of liver enzymes ALT, AST, ALP, G-GT and total bilirubin and MDA level were significantly enhanced by administration of acetaminophen and level of total protein while antioxidant enzymes "GR, GPx, CAT, SOD" were decreased. However, the pretreatment with The E. elaterium "fruit juice" at 1 ml/kg orally revealed attenuation of serum ALT, AST, ALP. The histopathological studies also supported the protective properties of E. elaterium "fruit juice". The area of necrosis and degeneration of hepatocytes were observed in the toxic group. The prophylactic and curative groups showed a marked protective effect with decreased necrotic zones and hepatocellular degeneration. The present results clearly demonstrate the marked antihepatotoxic effects of E. elaterium "fruit juice" extract through its antioxidant activity on acetaminophen induced hepatotoxicity in rats.DOI: http://dx.doi.org/10.3329/icpj.v3i5.18535 International Current Pharmaceutical Journal, April 2014, 3(5): 270-274


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