Hepatoprotective activity of picroliv, curcumin and ellagic acid compared to silymarin on paracetamol induced liver toxicity in mice (original) (raw)
Related papers
The Potential Effect of Silymarin Against Paracetamol-Induced Hepatotoxicity in Male Albino Rats
Pharmacognosy Journal
Background: Being the main metabolic organ, liver stays in touch with toxicity of introduced materials including, drugs. Protection is priceless to avoid complication of liver toxicity. Objectives: This research aimed to assess the protective impact of silymarin (SIL) on hepatotoxicity based on acute paracetamol (APAP) intoxication in rats in comparison with N-acetylcysteine (NAC). Methods: To do so serum was collected and the liver was analyzed for histological findings on rat model-paracetamol toxicity whether alone or in combination with SIL or NAC. The scenario was based on either preconditioning with SIL/NAC before induction of toxicity or afterwards. Serum liver function tests, pro-oxidant/antioxidant status, and proinflammatory markers were detected alongside liver histological study. Results: The results showed that liver function indices, oxidative state, and pro-inflammatory parameters were significantly changed, and histopathological alterations were detected in the liver of the intoxicated group. These modifications were inverted in groups treated with either SIL or NAC. The results of the current study suggested that SIL might be employed as a hepatoprotective drug against liver damage induced by APAP because of its ability to reduce lipid peroxidation, improve antioxidant defense status, and have anti-inflammatory effects. Conclusion: These results are equivalent to NAC therapy which is a standard drug against APAPrelated hepatotoxicity.
Environmental Science and Pollution Research, 2021
A multi-herbal combination (MHC) of ve herbs, namely Punica granatum L., Putranjiva roxburghii Wall., Swertia chirata Buch.-Ham., Tinospora cordifolia (Willd.) Miers and Trigonella corniculata L., was assessed against the paracetamol-induced acute hepatotoxicity in female Wistar rats. The animals were randomly assorted into seven groups with six animals in each group. The rats were pre-treated with MHC (50, 100, and 200 mg/kg bw) and silymarin (50 mg/kg bw) once daily for seven consecutive days via oral route followed by administration of paracetamol (3 g/kg bw) on day 7, an hour after the last administration of MHC and silymarin. It was observed that MHC administration signi cantly (p ≤ 0.05) overturned the paracetamolinduced increase in serum liver function biomarkers (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and total bilirubin), phase I reaction enzymes (NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase), and oxidant biomarkers (lactate dehydrogenase, lipid peroxidation, lipid hydroperoxides, and protein content). MHC administration also reinstated the paracetamol-induced signi cant decrease (p ≤ 0.05) in haematological indices (haematocrit, haemoglobin, red and white blood cells, and platelets), phase II reaction enzymes (glutathione-S-transferase and DT-diaphorase), membrane-bound enzymes (Na + /K +-ATPase, Ca 2+-ATPase, and Mg 2+-ATPase), and antioxidant biomarkers (reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). Overall, MHC at 200 mg/kg bw dose signi cantly (p ≤ 0.05) sheltered the red blood cells from the assault of free radicals, stabilized the structural and functional integrity of hepatocytes, hindered APAP biotransformation to its toxic metabolites, and endorsed conjugating abilities to detoxify toxic entities. Further, MHC signi cantly (p ≤ 0.05) activated enzymatic machinery to scavenge/inhibit the formation of reactive oxygen species, regulated nucleic acid metabolism, surface potential, and membrane uidity, attenuated tissue breakdown, quenched peroxyl radicals, and provided protection against tissue injury. The necroin ammatory scores revealed strong evidence of MHC (200 mg/kg bw) effectiveness against the paracetamol-induced hepatotoxicity in rats at p ≤ 0.05. The synergistic effect of major inherent phytoconstituents (kaempferol, ellagic acid, and gallic acid), detected by HPLC-PDA, in MHC might have overturned the paracetamol-induced biochemical toxic alterations in rat liver.
Journal of Applied Sciences and Environmental Management, 2019
This study aimed at assessing the in-vivo effect of Vitamin C on liver enzymes and some endogenous antioxidants in paracetamol-induced model of liver toxicity on Wistar rats. The rats were grouped into four groups of five animals each; groups 1 and 2 were control (positive and negative), while group 3 and 4 received vitamin C 500 mg/kg and silymarin 100 mg/kg respectively. Dosing was oral and daily for 6 days according to their body weights. All the animals except the positive control group (Group 1) were administered paracetamol 3 g/kg on the 7 th day, and then observed for 24 hours before sample collection for biochemical indices and liver histological studies. Paracetamol caused a significant (p<0.05) increase in liver enzymes, significant (p<0.05) decrease in antioxidant enzymes, and necrosis in liver tissues when compared to the control. Administration of 500 mg/kg Vitamin C prior to induction of liver damage by PCM resulted in significant (p<0.05) decreased liver enzyme and well as an increase in the antioxidant enzymes. Pre-treatment of the animals with vitamin C showed a reversal of the toxic effect of paracetamol on the rats.
International Journal of Anatomy and Research
Background: NSAIDs are the common group of drugs used in self-medication, and this is true for especially Paracetamol (acetaminophen).Although considered safe at therapeutic doses, in overdose, paracetamol causes centrilobular hepatic necrosis which can be fatal. As no data is available on the hepatoprotective effect of Costus pictus D Don, we have made an attempt to investigate the protective effect of Costus pictus D Don leaf extract on paracetamol induced liver damage in rats. The aim of the study is to compare the hepatoprotective effect of methanolic leaf extract of Costus pictus D Don and silymarin on liver damage induced by paracetamol in Wistar rats. Materials and Methods: 30 Healthy male adult Wistar rats (16 weeks old) weighing > 250g were used for the study. The animals were maintained in a standard cage under controlled temperature (25+2 °C) and light (12:12 light-dark cycle) in MGMC & RI central animal house. The animals were fed with standard rat pellet and hygienic water ad libitum. 30 adult Wistar rats were randomized into 5 groups with 6 rats each as (Normal control-0.5% carboxymethylcellulose (7 days), Toxic control-0.5% (7 days)+paracetamol 2g/kg(5 th day), Test group I-200 mg/ kg methanolic leaf extract+paracetamol 2g/kg(5 th day) , Test group II-100 mg/kg methanolic leaf extract+paracetamol 2g/kg(5 th day) & Standard group-silymarin 25mg/kg (7 days) + Paracetamol 2 g/kg (5 th day) The animals were sacrificed on 8 th day using sodium pentobarbitone 150mg/kg i.p. serum was sent for biochemical analysis for liver function test. Liver was harvested and a portion was taken for histological examination. Results: In our study methanolic leaf extract of Costus pictus D Don showed beneficial effect on paracetamol induced liver toxicity which was evident by the significant improvement in liver function test consisting of AST, ALT and ALP in a dose dependent manner which is in consistent with the histological findings. Conclusions: The study has proved the methanolic leaf extract of Costus pictus D Don posses a significant hepatoprotective activity which was comparable to the standard drug silymarin.
Drug-Induced Liver Toxicity and Prevention by Herbal Antioxidants: An Overview
Frontiers in Physiology, 2016
The liver is the center for drug and xenobiotic metabolism, which is influenced most with medication/xenobiotic-mediated toxic activity. Drug-induced hepatotoxicity is common and its actual frequency is hard to determine due to underreporting, difficulties in detection or diagnosis, and incomplete observation of exposure. The death rate is high, up to about 10% for drug-induced liver damage. Endorsed medications represented >50% of instances of intense liver failure in a study from the Acute Liver Failure Study Group of the patients admitted in 17 US healing facilities. Albeit different studies are accessible uncovering the mechanistic aspects of medication prompted hepatotoxicity, we are in the dilemma about the virtual story. The expanding prevalence and effectiveness of Ayurveda and natural products in the treatment of various disorders led the investigators to look into their potential in countering drug-induced liver toxicity. Several natural products have been reported to date to mitigate the drug-induced toxicity. The dietary nature and less adverse reactions of the natural products provide them an extra edge over other candidates of supplementary medication. In this paper, we have discussed the mechanism involved in drug-induced liver toxicity and the potential of herbal antioxidants as supplementary medication.
Hepatoprotective Properties of Selected Plants Against Paracetamol-Induced Hepatotoxicity in Mice
Journal of Institute of Science and Technology, 2017
The hepatoprotective properties of the ethanolic extracts of Punica granatum peels, Crataeva religiosa leaves and Jasminum polyanthrum leaves were evaluated for the paracetamol induced liver toxicity in mice. Antioxidant, cytotoxicity and phytochemical screening were carried out to assure the therapeutic efficacy of these plants. Oral administration of plant extracts for 7 days in mice significantly reduced the impact of paracetamol toxicity on the serum markers of liver damage, aspartate transaminase (AST), alanine transaminase (ALT) and total protein. The extract showed significant hepatoprotective effects as evidenced by decreased serum enzyme activities like ALT, AST and changed total protein. The phytochemical and antioxidant studies also supported that plant extract markedly reduced the toxicity due to presence of antioxidant phytochemicals. The result suggests that Jasminum polyanthrum is potent hepatoprotective agent against paracetamol induced hepatotoxicity in mice.
Aim: Different parts of Pseudocedrela kotschyi have been widely used by traditional healers for treatment of various illnesses, many of which have been scientifically scrutinized. However, this study aimed at evaluating anti-oxidative and hepato-protective potentials of its aqueous leaf (LEPK) and methanol bark (BEPK) extracts in paracetamol intoxicated rats. Methodology: Anti-oxidative and hepato-protective study was carried out by randomly dividing Thirty six (36) rats into nine groups with four (4) rats in each group. The route of administration was intraperitoneal, except Vitamin-C that was given orally. Group-1 received 5 ml/kg bwt single dose of Normal saline on the 6th day, Group-2 received a single dose of paracetamol (750 mg/kg bwt.) on 6th day. Group 3, 4 and 5 received 500, 250 and 500 mg BEPK /kg bwt. for 6 consecutive days. Group 6, 7 and 8 received 500, 250 and 500 mg LEPK/kg bwt. for 6 days. Group-9 received 500 mg vitamin-c/kg bwt. for 6 days. Group 4, 5, 7, 8 and 9 simultaneously received single dose of 750 mg paracetamol/kg bwt on the 6th day. Results: The degree of protection and antioxidative potentials was measured using histomorphological analysis and assessment of biochemical parameters such as, transaminases (ALT and AST), malonialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT). The doses studied produced various degree of hepato-protection by favourably altering biochemical parameters and showing histomorphological improvement. The effects of both extracts were comparable to that of standard vitamin-C. Conclusion: It has been observed that the extracts could protect the liver cells from paracetamol damage, perhaps, by its antioxidative effect. The extract produced a significant (p<0.05) dosedependent protection.
Objective: Amaranthus spinosus Linn. (Amaranthaceae), the leaves were boiled without salt and consumed for 2−3 days to cure jaundice used by tribal of Kerala (India). Methanol extract of whole plant of A. spinosus Linn, (MEAS) was screened for hepatoprotective potency against paracetamol (PCM) (3 gm/kg. o.p.) inducedliver damage in Wistar rats at dose of 200 and 400 mg/kg respectively. Materials and methods: A. spinosus was collected from surroundings of chickballapur, Karnataka (India). Whole plant was extracted with methanol. Hepatoprotective activity of MEAS was evaluated in PCM induced hepatotoxicity in Wistar rats by measuring liver marker serum enzymatic levels of serum glutamate oxaloacetate transaminase (AST), serum glutamate pyruvate transaminase (ALT), albumin (ALB), total protein (TP), total bilirubin, direct bilirubin levels and the markers for oxidative defense namely malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT) and total thiols (TT). Histopathological studies of liver were done to assess the cellular damage. Results: The results of our study showed significant (P<0.001) protection against PCM induced hepatic damage in experimental animals following the administration of MEAS. Our results were compared with silymarin (100 mg/kg), a known hepatoprotective drug. Conclusions: This presence of amino acids, flavonoids and phenolic compounds in the MEAS might be responsible for its marked chemoprotective and antioxidant activities in paracetamol induced-liver damage in Wistar rats.
Hepatoprotective effect of Phytosome Curcumin against paracetamol-induced liver toxicity in mice
Brazilian Journal of Pharmaceutical Sciences, 2017
Curcuma longa, which contains curcumin as a major constituent, has been shown many pharmacological effects, but it is limited using in clinical due to low bioavailability. In this study, we developed a phytosome curcumin formulation and evaluated the hepatoprotective effect of phytosome curcumin on paracetamol induced liver damage in mice. Phytosome curcumin (equivalent to curcumin 100 and 200 mg/kg body weight) and curcumin (200 mg/kg body weight) were given by gastrically and toxicity was induced by paracetamol (500 mg/kg) during 7 days. On the final day animals were sacrificed and liver function markers (ALT, AST), hepatic antioxidants (SOD, CAT and GPx) and lipid peroxidation in liver homogenate were estimated. Our data showed that phytosome has stronger hepatoprotective effect compared to curcumin-free. Administration of phytosome curcumin effectively suppressed paracetamol-induced liver injury evidenced by a reduction of lipid peroxidation level, and elevated enzymatic antioxidant activities of superoxide dismutase, catalase, glutathione peroxidase in mice liver tissue. Our study suggests that phytosome curcumin has strong antioxidant activity and potential hepatoprotective effects.
Revista Brasileira de Farmacognosia, 2015
Oxidative insult by free radicals has been implicated in drug-induced hepatic damage and this has resulted in frequent episodes of liver disorders. Therapeutic efficacy of antioxidants may provide a possible solution to this menace. This study was carried out to investigate the effect of combined administration of silymarin and vitamin C in rescuing acetaminophen-induced hepatotoxicity in rats. Hepatotoxic rats were orally administered with silymarin and vitamin C at 100 and 200 mg/kg body weight, respectively. At the end of the experiment, liver function indices, antioxidant parameters and histological analysis were evaluated. We observed that the significantly increased (p < 0.05) activities of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, as well as levels of thiobarbituric acid reactive substances and serum total bilirubin, were markedly reduced following co-administration of silymarin and vitamin C. The compounds also effectively reversed the reduced activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and total protein concentration in the hepatotoxic rats. These findings are indicative of hepatoprotective and antioxidant attributes of the two compounds which are also supported by the histological analysis. The available evidences in this study suggest that the complementary effects of silymarin and vitamin C proved to be capable of ameliorating acetaminophen-mediated hepatic oxidative damage and the probable mechanism is via antioxidative action.