High Doses Of Paracetamol Research Articles

Comparison of effects of high and low dose paracetamol treatment and toxicity on brain and liver in rats.

OBJECTIVE:Paracetamol is thought that it acts by inhibiting the central cyclooxygenase (COX) enzyme; its mechanism of action is still not fully explained. Although its most important side effect is hepatoxicity, it is thought to cause toxicity on the brain in recent years. The present study aims to investigate the treatment and toxic effects of low and high doses of paracetamol on the liver and brain.METHODS:Wistar-albino rats were used in this study. At doses of 20–500 mg/kg, paracetamol was administered intraperitoneally once a day for one and three days. The brain and liver were used for immunohistochemical evaluation using COX-3, prostaglandin E2 (PGE2) and caspase 3 antibodies and for total antioxidant (TAS), total oxidant (TOS) and oxidative stress index (OSI) measurements. Results were evaluated using the Kruskal Wallis test (SPSS ver.24).RESULTS:The liver COX-3 levels were significantly lower in both groups with higher doses (p<0.05). In the brain, there was no statistically significant difference in COX-3 levels between the groups. There was no statistically significant difference in PGE2 levels in the liver and brain between the groups (p>0.05). The caspase 3 level in the liver was statistically significantly higher in the low dose group compared to the other groups (p<0.05). In both liver and brain, OSI values were significantly higher in the 3-day high-dose group compared to others (p<0.05). There was no statistically significant difference between the groups in ALT and AST values (p>0.05).CONCLUSION:The results of our study show that paracetamol inhibits the COX-3 enzyme in the liver but has no effect in the brain, and COX-3 does not have an effect on PGE2. Paracetamol causes apoptosis in the liver only in low doses; higher doses may cause toxicity by increasing oxidative stress, especially in the brain.

THE ROLE OF L. METHIONINE, L. CARNITINE, CHOLINE AND/OR SILYMARIN IN HEPATOPROTECTION AGAINST PARACETAMOL INTOXICATION AND OXIDATIVE STRESS IN BROILERS

Paracetamol (Acetaminophen) was used for long time in poultry as an antipyretic drug and as a growth stimulator. However, high doses of paracetamol cause unpleasant side effects such as hepatorenal toxicity as mirrored by depletion of glutathione reserve, increase lipid peroxidation and increase liver enzymes or even sudden death with lethal doses. Therefore, this study was designated to evaluate the ameliorative effect of L. methionine, L. carnitine, choline and/or silymarin on the hepatotoxic effect induced by high doses of paracetamol. The study was applied on 80 chicks (from 1 till 33 days old) in special cages divided into 8 groups each one contained 10 chicks. The 1st group was used as a control, while the next 2-5 groups were supplemented with L. methionine, L. carnitine, choline and silymarin, respectively with doses as recommended by NRC, the 5th group was supplemented with silymarin (1 g/kg diet), the 6th group was supplemented with a mixture of the 4 supplements, the 7th group (hepatic intoxicated group) was given paracetamol (650 mg/kg diet for 7 days), and the 8th group was administrated paracetamol with a mixture of the 4 supplements. Serum samples were collected to determine levels of lipid profile [triglycerides (TG) and total cholesterol (TC)], liver damage enzymes [alanine transaminase (ALT), aspartate transferase (AST)], lipid peroxidation marker malondialdehyde (MDA), and activity of antioxidant enzymes [glutathione reductase (GR), superoxide dismutase (SOD)]. The obtained results revealed that there was a significant improvement in all measured serum biochemical parameters and final body weight gain in the combined group (4 supplements + paracetamol) as compared to the paracetamol group. These data conclude that supplementation of poultry diets with L. methionine, L. carnitine, choline and silymarin can improve the negative effect of paracetamol through increasing the body weight gain and antioxidant activity of glutathione and superoxide dismutase and decreasing malondialdehyde, liver enzymes, cholesterol and triglycerides.Key words: L. methionine; choline; L. carnitine; silymarin; hepatoprotection; broilers

Hepatoprotective Role of Green Tea, (Camellia senesis) Extract on Paracetamol Induced Hepatic Damage in Guinea-Pigs.

Aim: Green tea (Camellia senesis) is consumed because of the belief that it protects against liver related ailments. This study aims at finding the possible scientific basis for this claim. Methodology: Twenty guinea pigs of mixed sexes were divided into 4 experimental groups of 5 animals each. Group I served as a negative control for the liver marker-enzymes, aspartate-amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP). Total bilirubin (TB) and its metabolite, conjugated bilirubin (CB), were also estimated. In group II, a high dose of paracetamol was used to induce hepatotoxicity. In groups III and IV, the hepatotoxcity was challenged with the extract of a green tea at 100 and 200 mg/kg. Results: The results showed that the 100 mg/kg attenuated the serum levels of AST, ALT and ALP by 9.20, 7.30. and 5.10 % respectively. The inhibition of ALT was significant (p&lt;0.05). The 200 mg/kg reduced the levels of the enzymes for AST by 12.00, 9.70 and 5.30% respectively (p&gt;0.05). The serum CB was also significantly reduced by the two doses of the extract (p&lt;0.05). The actual mechanism by which these occurred was not known. Conclusion: The extract of the green tea may possess hepatoprotective effects. Key words: Hepatoprotection. Liver enzymes, Green tea. (Camellia senesis). Guinea- pig

PHARMACOLOGICAL ACTIVITY OF ULVA LACTUCA POLYPHENOLS FRACTION: HEPATOPROTECTIVE AND ANTIOXIDANT ACTIVITIES AGAINST PARACETAMOL-INDUCED LIVER DAMAGE IN RATS

Objective: The objective of this study was to assess the activity Ulva lactuca polyphenols fraction in protecting the liver damage induced by high dose of paracetamol.&#x0D; Methods: This study was performed using Wistar albino rats divided into six groups. Group 1 was the normal group. Groups 2, 3, 4, 5, and 6 received paracetamol (2 g/kg) for 7 days. In addition to paracetamol, Groups 3, 4, 5, and 6 received silymarin (100 mg/kg), U. lactuca polyphenols fraction at the doses of 50, 100, and 200 mg/kg, respectively, for 7 days. On the 8th day, serum and liver samples were collected from the animals and the hepatoprotective and antioxidant activities were assessed by studying the levels of liver marker enzymes, bilirubin, protein, reduced glutathione, and antioxidant enzymes.&#x0D; Results: U. lactuca polyphenols fraction, at the tested doses, restored the levels of all serum markers and enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase, total bilirubin, total protein, cholesterol, triglycerides, and reduced glutathione) and liver homogenate markers (reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase) significantly, in dose-dependent manner.&#x0D; Conclusion: This study suggests that U. lactuca polyphenols fraction has a hepatoprotective effect against paracetamol-induced liver damage and possesses antioxidant activities.

Hepato-Protective Studies of Poloxamer-188 by Paracetomol induced liver toxicity in Rats

Poloxamer-188 (P-188) is a polymer well renowned for possessing medical properties. Present study was conducted with an aim to evaluate Hepato-protective potential of P-188 against paracetamol induced liver damage in wistar albino rats. Group-I served as Normal control which received normal saline 5ml/kg of Body weight (BW) for 7 days. Group-II served as Negative control in which animals received same dose as mentioned in Group-I. Group-III, IV and V animals received P-188(50mg/kg), P-188(100mg/kg) and silymarin (25mg/kg) respectively for 7 days. Except Group-I all other groups challenged with a very high dose of paracetamol (750 mg/kg) to induce hepatotoxicity. Biochemical estimation results showed that SGOT, SGPT and ALP levels were increased in negative control group animals which were decreased to normal levels when treated with P-188. There was highly significant (p<0.0001) decrease of these values in all three treatment groups. Moreover decrease in P-188 treated groups is dose dependent. Histopathological study supports the results of biochemical estimation. Negative control animal showed inflammation with mild cholestasis. P-188 (50mg/kg) showed mild inflammation, more number of normal hepatocytes, whereas P-188 (100 mg/kg) showed scattered lymphocytes among normal hepatocytes and kupffer cell hyperplasia, no incidence of inflammation and necrosis. Based on these results we can conclude that P-188 is a hepatoprotective polymer.

The Effect of Roselle (Hibiscus sabdariffa Linn) Flower Extract To The SGPT Activity In Male Wistar Rats (Rattus Norvegicus) Induced By High Dose Paracetamol

Paracetamol is an analgesic drug that is used widely. The use of high dose paracetamol can cause liver damage. Based on research, Roselle has high antioxidant content.The objective of the research was to find out the effect of Roselle (Hibiscus sabdariffa Linn) flower extract to the SGPT activity of Wistar rats induced by high dose paracetamol.This study used 24 male Wistar rats as samples and conducted for 10 days. Samples were divided into 3 groups : group of rats fed with standard diet and filtered water for 10 days and received 0.5% CMC-Na orally on the 9th day; group of rats fed with standard diet filtered water for 10 days and received paracetamol 1750mg/kg body weight (in 0.5% CMC-Na) orally on the 9th day; group of rats fed with standard diet and Roselle flower extract 200mg/kg body weight for 10 days and received paracetamol 1750mg/kg body weight (in 0.5% CMC-Na) orally on the 9th day. All group were sacrified on the 10th day. SGPT activity were examinated with spectrophotometry method.The result of Kruskal-Wallis test showed significant difference (p=0.001) of SGPT activity between the group of rats received standard diet (81,44 U/L) and group of rats received high dose paracetamol (240,39 U/L). Furthermore, there is significant difference (p=0.001) of SGPT activity between group of rats received high dose paracetamol (240,39 U/L) and group of rats received high dose parasetamol and Roselle flower extract (72,98 U/L).It can be concluded that high dose of paracetamol significantly increased SGPT activity, and Roselle flower extract significantly reduced SGOT activity of Wistar rats induced by high dose parasetamol.

Hepatoprotective Activity of Curcuma mangga Extract on Paracetamol-Induced Male Mice

This study was carried out to investigate the protective effect of ethanol extract of Curcuma mangga rhizomes on paracetamol-induced hepatotoxicity. High dose of paracetamol (1.35g/kg bw) was used to induce hepatic necrosis of mice liver. The male mice received ethanol extract of C. mangga rhizomes (100, 200 and 400 mg/kg BW) for 7 days. The hepatoprotective actvity of extract was compared to normal, positive (curcuma) and negative control. The liver function was evaluated by measuring the biochemistry parameters which include alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, histophatological study on hepatic tissue section was also carried out. The C. mangga extract displayed hepatoprotective effect except at dose of 100 mg/kg bw. The increasing of serum levels of AST and ALT were inhibited after treatment with ethanol extract at doses of 200 and 400 mg/kb bw which was comparable with normal and curcuma as postive control (p&gt;0.05). In addition, histological assessment of hepatic tissue demonstrated no liver damage, specially at dose of 400 mg/kb BW. The result indicate that ethanol extract of C. mangga rhizomes has hepatoprotective effect, especially at doses of 200 and 400 mg/kg bw .&#x0D; &#x0D; Keywords: C. mangga, rhizomes, biochemistry parameters, histopathology

Aktivitas Hepatoprotektif Ekstrak Metanol Buah Lakum (Cayratia trifolia (L.) Domin) Terhadap Diameter Vena Sentralis, Lebar Sinusoid dan Berat Hepar Tikus Putih (Rattus novergicus L.) yang Diinduksi Parasetamol

Secondary metabolites of lakum (Cayratia trifolia (L.) Domin) fruit have been evaluated in previous researches. The fruit contains flavonoids, terpenoids and phenols which have antioxidant properties. The aim of this research was to determine the hepatoprotective activity of methanolic extract of lakum fruit in Wistar rats’ liver induced by high doses of paracetamol. Ripe lakum fruits were macerated with methanol as the solvent. Thirty-five male Wistar rats (Rattus novergicus L.) were used in this research and devided into 7 groups (normal, negative, positive, solvent, 115 mg kg-1, 230 mg kg-1, and 345 mg kg-1 of lakum fruit methanolic extract). Results showed that the effect of 230 mg kg-1 of lakum fruit methanolic extract (central vein diameter: 40,20 ± 6,97 µm; sinusoid wide: 5,60 ± 0,94 µm; and liver weight: 6,33 ± 0,98 g) were similar to the effect of silymarin (central vein diameter: 42,99 ± 6,60 µm; sinusoid wide: 4,49 ± 0,44 µm; and liver weight: 6,58 ± 0,88 g) as the standard drug.

Influence of Eclipta alba on serum alanine aminotransferase and aspartate aminotransferase activity in rabbits

Background: Paracetamol is a recognized antipyretic, analgesic drug which produces hepatic necrosis in high doses. Eclipta alba elaborates a vast array of biologically active compounds that are chemically diverse and structurally complex.Methods: Randomized open controlled experimental study Estimated levels of Serum aspartate aminotransferase (AST), Serum alanine aminotransferase (ALT) and Hepatoprotective action of in High doses of Paracetamol on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity.Results: ALT in all the groups including Control group (A) was (51.8±4.56IU/L). Paracetamol treated group (B) the ALT level increased at 48 hours and continued to be high up to 60 days (136.4±20.73IU/L) then decreased to (113.7±11.35IU/L) at 90 days. AST in all the groups including Control group (A) was (22.5±1.23IU/L). Appropriate antioxidant in appropriate doses as a matter of routine whenever hepatotoxic or potentially hepatotoxic drugs are prescribed. In Paracetamol treated group (B) the AST level increased at 48 hours and continued to be high up to 60 days (99.4±9.73IU/L) then decreased to (85.4±7.39IU/L) at 90 days.Conclusions: Appropriate antioxidant in appropriate doses as a matter of routine whenever hepatotoxic or potentially hepatotoxic drugs are prescribed.

Pengaruh Pemberian Ekstrak Kulit Buah Alpukat (Persea Americana) Terhadap Kadar Malondialdehida (MDA) Jaringan Hepar Tikus Putih (Rattus norvegicus) Jantan Galur Wistar yang Diinduksi Parasetamol Dosis Tinggi

&lt;p&gt;Administration of high-dose paracetamol may increase metabolic pathways that produce N-acetyl-p-benzoquinonimine (NAPQI). NAPQI is reactive substance, resulting in hepatic tissue damage and increase liver MDA level. Avocado peel extract contains flavonoids that act as antioxidants so it is expected may decrease liver MDA level of high-dose paracetamol administration.&lt;/p&gt;&lt;p&gt;This research used 24 male Wistar rats divided into 3 groups: group of rats fed with standard food, group of rats given paracetamol 1,750 mg/kg BW on day 8, and group of rats given avocado peel extract 1,400 mg/kg/day for 8 days and paracetamol 1750mg/kg BW on day 8. Liver MDA levels were checked on day 9 by thiobarbituric acid&lt;em&gt; &lt;/em&gt;(TBA) method.&lt;/p&gt;&lt;p&gt;The One-Way ANOVA test showed that the liver MDA level of the group of rats given high dose of paracetamol (=312.38±47.830 nmol/g) was significantly higher (p = 0.001) compared to the liver MDA level of the group of rats fed with standard food (=184.50±57.021 nmol/g). The liver MDA level of group of rats given high-dose paracetamol and avocado peel extract&lt;em&gt; &lt;/em&gt;(=268.50±91.834 nmol/g) did not significantly decrease (p =0.213) compared to the liver MDA level of group of rats given high dose of paracetamol (=312.38±47.830 nmol/g).&lt;/p&gt;&lt;p&gt;The conclusion of this research showed that high-dose paracetamol significantly increased liver MDA level and avocado peel extract tend to decrease liver MDA level because avocado peel consists flavonoid, hydroxynnamic acid&lt;em&gt;, &lt;/em&gt;keratinoid, vitamin C, dan vitamin E that function as antioxidants.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;&lt;strong&gt;Keywords&lt;/strong&gt;: &lt;em&gt;Paracetamol, MDA, Persea americana&lt;/em&gt;&lt;/p&gt;

Pengaruh Pemberian Cuka Apel 'A' terhadap Kadar MDA Hepar Tikus Wistar Jantan yang Diinduksi Parasetamol Dosis Toksik

&#x0D; High dose of paracetamol is metabolized by cytochrome P-450 become free radical N-acetyl-p-benzoquinoneimine (NAPQI) but liver Glutathione (GSH) is not adequate to change it become nonreactive metabolite so that NAPQI bind to unsaturated fatty acid of cell membrane, causing lipid peroxidation and increase liver Malondialdehyde (MDA). 'A' apple vinegar contains anthocyanin with an antioxidant effect by electron donor to NAPQI and acetic acid to improve liver GSH level. The aim of research was to investigate the effect of 'A' apple vinegar on the rat liver MDA induced by toxic dose of paracetamol. Research groups consist of normal control (CMC Na 1% 1 ml for 14 days), negative control (CMC Na 1% 1ml for 14 days + paracetamol 291.6 mg/200gBW on the day 12nd,13rd,14th), and treatment group ('A' apple vinegar 0.4 ml/150gBW for 14 days + paracetamol 291.6 mg/200gBW on the day 12nd,13rd,14th). Liver MDA was measured on the day 15th with competitive ELISA. The average of normal control group was 21.58 ng/ml, negative control group was 70,71 ng/ml, treatment group was 37,67 ng/ml. One way ANOVA and Post hoc LSD test showed significantly differences between all groups (p&lt;0,05). It can be concluded that 'A' apple vinegar had an effect on the liver MDA induced by toxic dose of paracetamol.&#x0D; &#x0D; Keywords: Paracetamol, NAPQI, MDA, 'A' apple vinegar, antioxidant&#x0D;

Pengaruh Pemberian Ekstrak Alga Merah (gracilaria verrucosa) terhadap Aktivitas SGPT pada Tikus Putih (rattus norvegicus) Jantan Galur Wistar yang Diinduksi Parasetamol Dosis Tinggi

Background: Administration of high dose paracetamol may increase the metabolic pathways that produce N-acetyl-p-benzoquinonimin (NAPQI). NAPQI is a reactive substance, resulting liver tissue damage and increase SGPT activity. Red algae extract contains flavonoids that act as antioxidants.Objectives: This research aimed to determine the effect of red algae (Gracilaria verrucosa) extract to the activity of serum glutamic pyruvic transaminase (SGPT) in male Wistar rats (Rattus norvegicus) induced by high dose paracetamol.Methodology: This research used 24 animal of Male Wistar rats. These rats were divided into 3 groups: 1) group of rats fed with standard food; 2) group of rats given paracetamol 1750 mg/kg on day 10; and 3) group of rats given red algae extract 200 mg/kg/day on day 1-11 and paracetamol 1750mg/kg on day 10. On day 11, all rats were sacrificed and SGPT activities were measured by spectrophotometry method.Result: Mann-Whitney test results showed significant difference (p = 0.021) between SGPT activity of group of rats fed with standard food (=81.95±10.103 U/L) and group of rats induced by high dose paracetamol (=97.06±11.19 U/L). Furthermore, there was significant difference (p = 0.016) between SGPT activity of group of rats induced by high dose paracetamol (=97.06±11.19 U/L) and group of rats induced by high doses of paracetamol and fed with red algae extract (=82.73±11.233 U/L).Conclusion: The conclusion of this research showed that high dose paracetamol significantly increased SGPT activity and red algae extract significantly decreased SGPT activity because it contains flavonoids that act as antioxidants.

Anxiety- and activity-related effects of paracetamol on healthy and neuropathic rats.

Paracetamol has recently been suggested to affect emotion processing in addition to alleviating pain in humans. We investigated in adult male Hannover–Wistar rats whether acute intraperitoneally administrated paracetamol affects behavior in tests measuring anxiety, mood, motor activity, and memory. Unoperated rats received saline or a low (50 mg/kg) or high (300 mg/kg) dose of paracetamol, while rats with a spared nerve injury (SNI) model of neuropathy and sham‐operated rats received saline or the low dose of paracetamol. Rats were tested on open‐field (OFT), elevated plus‐maze (EPM), light‐dark box (LDB), novel‐object recognition (NOR), sucrose preference, rotarod, and monofilament tests. In unoperated rats, both the low and high dose of paracetamol reduced line crossings, and grooming time in the OFT, and novel preference in NOR. The high dose of paracetamol increased the time spent in the closed arm in EPM, reduced the number of rearings and leanings in OFT, the time spent in the light box in LDB, and sucrose preference. Paracetamol had no significant effect on the rotarod test measuring motor activity. The low dose of paracetamol suppressed mechanical pain hypersensitivity in SNI rats, without influencing pain behavior in sham‐operated rats. Saline‐ but not paracetamol‐treated SNI rats spent more time than sham‐operated rats in the closed arm in the EPM test. Together the results suggest that a high dose of paracetamol increases anxiety‐like and anhedonic behavior, and impairs recognition memory in unoperated controls, while in neuropathy, a low dose of paracetamol reduces nerve injury‐associated anxiety probably by reducing neuropathic pain.

The Lipid Lowering and Cardioprotective Effects of Vernonia calvoana Ethanol Extract in Acetaminophen-Treated Rats.

Background: Paracetamol overdose/abuse as a result of self-medication is a common occurrence amongst people living in low/middle income countries. The present study was designed to investigate the hypolipidemic and cardioprotective potentials of Vernonia calvoana (VC) ethanol extract in acetaminophen (paracetamol)-treated rats. Methods: Thirty-five Wistar rats weighing 100–150 g were randomly assigned into five groups of seven rats each. Groups 2–5 received high doses of paracetamol to induce liver damage, while group 1 was used as normal control. Afterwards, they were allowed to receive varying doses of VC (group 3 and 4) or vitamin E (group 5), whilst groups 1 and 2 were left untreated. The treatment period lasted for twenty one days after which sera were harvested and assayed for serum lipid indices using standard methods. Results: Groups 3 to 5 treated animals indicated significant decrease (p < 0.001) in low density lipoprotein cholesterol (LDL-c), total cholesterol (TC) and triacylglycerol (TG) levels relative to the normal and acetaminophen-treated controls, the atherogenic index showed a significant decrease (p < 0.001) in all treated groups compared with normal and acetaminophen-treated controls. However, the VC- and vitamin E-treated groups showed significant (p < 0.001) increase in high density lipoprotein cholesterol (HDL-c) relative to the controls. Conclusions: Data from our study suggest that ethanol leaf extract of VC possesses probable hypolipidemic and cardioprotective effects.

HEPATOPROTECTIVE ACTIVITY FROM ETHANOL EXTRACT OF PUGUN TANO’S LEAVE (Curanga fel-terrae (Lour.) Merr.)

Objective: The aim of this study is to observe the activity of ethanol extract of Curanga fel-terrae leave in preventing the damaged of liver which is induced by high dose of paracetamol. Methods: This research was conducted by using Wistar rat divided into 6 groups. Group 1 was the normal group. Group 2, 3, 4, 5 and 6 received CMC-Na 0.5% (negative control), C. fel-terrae ethanolic extract (CFEE) at the doses of 125, 250 and 500 mg/kg, catechin 2 mg/kg (positive control),respectively during 7 days continued and followed by given paracetamol dose of 2.5g/kg 8 hours after that. Hepatoprotective activity was carried out toward parameter of AST, ALT as well as histopathology of the liver. Results: The results showed that high-dose paracetamol dose of 2.5g/kg bw can cause liver damaged which can be seen by the increasing of the level of AST and ALT compared to the normal group (p&lt;0.05). The usage of three doses of CFEEfor 7 days showed the prevention of the increasing of the level of AST and ALT compared to negative control group (p&lt;0.05). Furthermore, the histopathology study revealed that the three doses of extract could protect the liver. Conclusion: The C. fel-terrae ethanolic extract (CFEE) at the doses of 125, 250 and 500 mg/kg bw which was given for 7 days can prevent the liver from the damage caused by high-dose of paracetamol. Keyword: Curanga fel-terrae (Lour.) Merr., paracetamol, liver, hepatoprotective

Restorative effects of Chrysin pretreatment on oxidant-antioxidant status, inflammatory cytokine production, and apoptotic and autophagic markers in acute paracetamol-induced hepatotoxicity in rats: An experimental and biochemical study.

Paracetamol (PC) is a widely used analgesic and antipyretic drug, but it leads to acute hepatotoxicity at high doses intakes. This study was aimed to investigate the effects of Chrysin (CR) on hepatotoxicity constituted at high doses of PC in rats. Rats were subjected to oral pretreatment of CR (25 and 50mg/kg b.w.) via feeding needle for 6 days against hepatotoxicity induced by a single dose of PC (500mg/kg b.w.) administered orally via feeding needles. Although PC increases lipid peroxidation and liver enzyme activities, it has led to reduction of antioxidant enzyme activities. PC induced inflammatory responses by increasing the levels of TNF-α and IL-1β. Furthermore, PC caused apoptosis and autophagy by increasing activity of Caspase-3 and LC3B level. On the other hand, CR therapy significantly regulated these values in rats. This study demonstrated that CR possesses restorative effect against PC-induced hepatotoxicity by suppressing oxidative stress, inflammation, and apoptotic and autophagic tissue damage.

P13.04: Constriction of the fetal ductus arteriosus associate with high doses of paracetamol: two cases and review of the literature

P13.04: Constriction of the fetal ductus arteriosus associate with high doses of paracetamol: two cases and review of the literature

AUDIT OF PARACETAMOL PRESCRIPTIONS IN PAEDIATRIC SURGICAL PATIENTS

AimLocal Guidelines for peri-operative pain management in children published in 2012 recommended that paracetamol dosing was calculated using ideal body weight (IBW) to prevent inadvertent overdosing in overweight and obese...

Hepatoprotective Effect of Captopril on Liver Toxicity Induced by High and Low Dose of Paracetamol in Rats:Histological Study

Many patients may administered medications like captopril (ACE inhibitor) for treatment of chronic diseases and may also take Paracetamol as an Over The Counter (OTC) drug which may interact with captopril. Therefore, the aim of this study is to evaluate of the hepatoprotective effect of captopril on liver toxicity induced by low and high dose of paracetamol in rats. This study was conducted in two phases: first study for low dose of paracetamol (300 mg/kg); animals were divided into 4 groups of 6 rats each (n = 6); all groups were treated orally either 0.9 % Normal Saline (NS), captopril 20 mg/kg, paracetamol 300 mg/kg or captopril 20 mg/kg plus paracetamol 300 mg/kg for 10 consecutive days. Second study for single high dose of paracetamol (3000 mg/kg); animals were divided into 4 groups of 6 rats each (n = 6); all groups were pretreated orally either 0.9 % Normal Saline (NS) or captopril 20 mg/kg for 7 consecutive days followed by single oral administration of Paracetamol 3000 mg/kg or normal saline. The administration of Paracetamol or normal saline was performed 24 hours after the last administration of captopril. After 48 hours of hepatic injury induction, the animals were then sacrificed and the liver was removed for histopathological studies. Low dose (300 mg/kg) for 10 days and high single dose (3000 mg/kg) of paracetamol produced hepatotoxic effects. While captopril 20 mg/kg showed marked protection against changes induced by low and high dose of paracetamol on the liver.

Epaltes divaricata in paracetamol poisoning: a biochemical and histopathological investigation

Introduction and Objective: In the practice of traditional ayurvedic medicine in Sri Lanka, a number of herbs have been recognized for their potential benefits in the treatment of liver disorders. This study was conducted to investigate the protective effect of Epaltes divaricata plant extract in paracetamol induced hepatotoxicity in mice. Methods: ICR mice (n=20) were treated with acetaminophen at a single dose of 300 mg/kg (after a 16h fast) to induce hepatotoxicity. Drug control group and pre and post-treated groups were administered 0.9 g/kg of Asparagus falcatus orally. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatise (ALP) and liver reduced glutathione (GSH) levels were determined. Liver damage was also assessed histopathologically. The effect of the plant extract was compared with N-acetyl cysteine. Results:Acetaminophen produced liver damage, as manifested by a significant rise (P Discussion: This study shows the ability of the aqueous extract of Epaltes divaricata to preserve liver functions in mice treated with high dose of paracetamol. Galle Medical Journal 2015 20(1): 1-7