Monika Bhadauria

Multiple treatment of propolis extract ameliorates carbon tetrachloride induced liver injury in rats

Propolis, a resinous wax-like beehive product has been used as a traditional remedy for various diseases due to a variety of biological activities of this folk medicine. In the present investigation, an attempt has been made to validate hepatoprotective activity of ethanolic extract of propolis (50-400mg/kg, p.o.) against carbon tetrachloride (CCl(4,) 0.5 ml/kg, p.o.) induced acute liver injury in rats. Silymarin, a known hepatoprotective drug was used as a positive control. Administration of CCl(4) altered various diagnostically important biochemical variables. Multiple treatment of propolis significantly prevented the release of transaminases, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transpeptidase, urea and uric acid in serum; improved the activity of hepatic microsomal drug metabolizing enzymes, i.e., aniline hydroxylase and amidopyrine-N-demethylase; significantly inhibited lipid peroxidation and markedly enhanced glutathione in liver and kidney as well as brought altered carbohydrate contents (blood sugar and tissue glycogen), protein contents (serum, microsomal and tissue protein) and lipid contents (serum and tissue triglycerides, serum cholesterol, total and esterified cholesterol in tissue) towards control. Propolis treatment also reversed CCl(4) induced severe alterations in histoarchitecture of liver and kidney in a dose dependent manner. Hepatoprotective activity of propolis at doses of 200 and 400 mg/kg was statistically compared to silymarin and found that propolis exhibited better effectiveness than silymarin in certain parameters, concluded its hepatoprotective potential.

Hepatoprotective activity of Woodfordia fruticosa Kurz flowers against carbon tetrachloride induced hepatotoxicity

ETHNOPHARMACOLOGICAL RELEVANCE Dried flowers of Woodfordia fruticosa Kurz. Family Lythraceae are used in variety of diseases in traditional Indian system of medicine including hepatic ailments. AIMS OF STUDY The aim of present study was to validate hepatoprotective activity of flowers of Woodfordia fruticosa Kurz. MATERIALS AND METHODS Petroleum ether (WF1), chloroform (WF2), ethyl alcohol (WF3) and aqueous (WF4) extracts of the flowers of Woodfordia fruticosa were evaluated for hepatoprotective activity against carbon tetrachloride induced hepatotoxicity using biochemical markers, hexobarbitone sleep time, bromosulphalein (BSP) clearance test and effect on bile flow and bile solids. RESULTS The aqueous extract (WF4) was most potent among the four extracts studied in detail. WF4 showed significant hepatoprotective activity against carbon tetrachloride induced hepatotoxicity as evident by restoration of serum transaminases, alkaline phosphatase, bilirubin and triglycerides. The restoration of microsomal aniline hydroxylase and amidopyrine-N-demethylase activities indicated the improvement in functional status of endoplasmic reticulum. Restoration of lipid peroxidation and glutathione contents suggests the antioxidant property of WF4. The recovery in bromosulphalein clearance and stimulation of bile flow suggested the improved excretory and secretary capacity of hepatocytes. Light microscopy of the liver tissue further confirmed the reversal of damage induced by hepatotoxin. CONCLUSION Present study showed that the aqueous extract of Woodfordia fruticosa significantly restores physiological integrity of hepatocytes. WF4 did not show any sign of toxicity up to oral dose of 2g/kg in mice.

Dose-dependent hepatoprotective effect of emodin against acetaminophen-induced acute damage in rats.

Protective effect of emodin (1,3,8-trihydroxy-6-methyl anthraquinone), an active compound of Ventilago madraspatana Gaertn., was evaluated against acetaminophen-induced biochemical and histological alterations in rats. Acetaminophen (2g/kg, po) administration caused significant elevation in the release of serum transaminases, alkaline phosphatase, lactate dehydrogenase, serum bilirubin and serum protein with concomitant decrease in hemoglobin and blood sugar after 24h of its administration. Toxicant exposure intensified the lipid peroxidation and altered glutathione status, activities of adenosine triphosphatase, acid phosphatase, alkaline phosphatase as well as major cellular constituents i.e., protein, glycogen and total cholesterol in liver and kidney. Treatment of emodin (20, 30 and 40 mg/kg, po) significantly lessened the toxicity by protecting acetaminophen-induced alterations in various blood and tissue biochemical variables after 24h of its administration. Acetaminophen administration initiated histological damage in liver. Some degree of protection was seen after emodin therapy in a dose-dependent manner. Emodin at doses of 30 and 40 mg/kg effectively reversed toxic events induced by acetaminophen as same as silymarin (50mg/kg, po). Thus, the study concluded that emodin at a dose of 30 mg/kg (po) possesses optimum hepatoprotective ability against acetaminophen-induced toxicity.

Propolis reverses acetaminophen induced acute hepatorenal alterations: A biochemical and histopathological approach

The present study has been conducted to evaluate the curative effect of propolis extract, a honey bee-hive product, against acetaminophen (APAP) induced oxidative stress and dysfunction in liver and kidney. Animals were challenged with APAP (2 g/kg, p.o.) followed by treatment of propolis extract (100 and 200 mg/kg, p.o.) once only after 24 h. Release of transaminases, alkaline phosphatase, lactate dehydrogenase, and serum bilirubin were increased, whereas hemoglobin and blood sugar were decreased after APAP administration. Antioxidant status in both the liver and kidney tissues were estimated by determining the glutathione, malondialdehyde content and activities of the CYP enzymes, which showed significant alterations after APAP intoxication. In addition, activities of adenosine triphosphatase, acid phosphatase, alkaline phosphatase, and major cell contents (total protein, glycogen and cholesterol) were also altered due to APAP poisoning. Propolis extract successfully reversed the alterations of these biochemical variables at higher dose. Improvements in hepatorenal histoarchitecture were also consistent with biochemical observations. The results indicated that ethanolic extract of propolis has ability to reverse APAP-induced hepatorenal biochemical and histopathological alterations probably by increasing the antioxidative defense activities due to various phenolic compounds present in it.

Duration-dependent hepatoprotective effects of propolis extract against carbon tetrachloride-induced acute liver damage in rats.

Propolis is a natural product produced by bees that was discovered through the study of traditional cures and knowledge of indigenous people throughout the world. It is rich in vitamins A, B, C, and E, and in amino acids, copper, iron, manganese, and zinc. The investigators studied the duration-dependent hepatoprotective effects of propolis extract (200 mg/kg, orally) against carbon tetrachloride (CCI4; 1.5 ml/kg, intraperitoneally)-induced liver damage in rats. Administration of CCI4 caused a sharp elevation in the activity of serum transaminases and serum alkaline phosphatase. A significant depletion in hepatically reduced glutathione was observed with significantly enhanced hepatic lipid peroxidation. After CCI4 administration, glycogen contents and activities of alkaline phosphatase, adenosine tri phosphatase, and succinic dehydrogenase were significantly decreased, whereas total protein contents and activity of acid phosphatase were increased in the liver and kidney. Propolis extract reversed alterations in all parameters when administered within 6, 12, and 24 h of toxicant exposure. Propolis therapy produced duration-dependent protection, with maximal protection achieved at 24 h after CCI4 exposure. It is believed that propolis in its natural form has general pharmacologic value and marked hepatoprotective potential because of its composition of minerals, flavonoids, and phenolic compounds.

Reversal of acetaminophen induced subchronic hepatorenal injury by propolis extract in rats.

The ethanolic extract of propolis (200mg/kg, p.o.) was evaluated against acetaminophen (APAP; 20mg/kg, p.o.) induced subchronic hepatorenal injury in rats. Administration of APAP significantly increased the release of serum transaminases, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transpeptidase, bilirubin and serum proteins, whereas concomitantly decreased hemoglobin, blood sugar and albumin. Hepatorenal reduced glutathione and activities of superoxide dismutase and catalase, hepatic CYPs i.e., aniline hydroxylase and amidopyrine-N-demethylase were significantly decreased after APAP intoxication. Lipid peroxidation showed significant elevation in both organs significantly after APAP assault. Total proteins, glycogen contents and the activities of certain metabolic enzymes i.e., adenosine triphosphatase, alkaline phosphatase and acid phosphatase were altered after APAP administration. Propolis extract exhibited curative effects by reversing APAP induced alterations in blood biochemical variables, CYP enzymes and markers of oxidative stress. Histopathological analysis of liver and kidney was consistent with the biochemical findings and led us to conclude the curative potential of propolis against APAP induced hepatorenal injury.

Combined treatment of HEDTA and propolis prevents aluminum induced toxicity in rats.

A study was undertaken to evaluate protective effect of chelating agent, N-(2-hydroxy ethyl ethylene diamine triacetic acid) [HEDTA] with and without propolis against aluminum (Al) induced toxicity in liver, kidney and brain. Toxicity was induced by single administration of aluminum nitrate at a dose of 32.5mg/kg (½ of LD(50)). HEDTA (20mg/kg, ip), propolis (200mg/kg, po), and combination of HEDTA and propolis, respectively, were administered for 3 days after 24h of Al exposure. Significant enhancement in AST, ALT, uric acid, urea, cholesterol, and triglyceride contents was found in serum, whereas albumin was decreased after Al exposure. Hepatic, renal, and neuronal LPO were found significantly increased after Al exposure, whereas it inhibited AChE activity in forebrain, midbrain, and hindbrain. Al significantly reduced the activity of adenosine triphosphatase, superoxide dismutase and catalase and GSH contents in hepatic, renal and nervous tissues. However, individual treatment of HEDTA and propolis restored biochemical parameters towards control but combined treatment of HEDTA and propolis offered better protection in comparison to monotherapy. Combined treatment of HEDTA and propolis preserved histological features, mitigated oxidative stress and improved liver, kidney and brain functions more profoundly.

Therapeutic potential of thymoquinone against anti-tuberculosis drugs induced liver damage.

Hepatotoxicity is the most serious adverse effect related to tuberculosis treatment which interrupts the successful completion of tuberculosis treatment. The purpose of this study was to assess therapeutic effect of thymoquinone (TQ) against anti-tuberculosis drugs (ATD) induced liver damage. Rats were treated with ATD for 8 weeks (3 days/week) as given for the treatment of TB. This was followed by therapy of TQ for 8 weeks (3 days/week). Administration of combined ATD induced hepatotoxicity was evident from a significant elevation in the AST, ALT, ALP, bilirubin, albumin, cholesterol, urea, uric acid, creatinine, LPO and decreased activities of enzymes. These altered variables were significantly reversed toward control after treatment with TQ. Histological studies also supported biochemical findings. Results of this study strongly indicated protective effect of TQ and thus, can be expected as promising protective agent in maintenance of normal hepatic function during treatment with ATD.

Baicalin prevents cadmium induced hepatic cytotoxicity, oxidative stress and histomorphometric alterations

Therapeutic potential of baicalin was evaluated against Cd-induced hepatic cytotoxicity and oxidative stress. Exposure to Cd (cadmium chloride) in Chang liver cell culture produced cytotoxicity in terms of increase in cell growth inhibition rate, alanine aminotransferase, lactate dehydrogenase, and cellular lipid peroxidation, which was significantly mitigated by baicalin in a concentration dependent manner. Acute exposure to Cd (6.5 mg/kg body weight; ip once only) produced a condition of oxidative stress in rats and substantially increased LPO and GSSG level along with corresponding decrease in GSH and various antioxidant enzymes in liver and also increased the leakage of liver marker enzymes in serum. Therapy with baicalin after 3 h of Cd administration inhibited LPO and formation of GSSG along with increase in liver GSH level. Release of serum transaminases, alkaline phosphatase and lactate dehydrogenase were significantly restored towards control after baicalin treatment. Administration of baicalin helped in restoring the activities of antioxidants enzymes, i.e., superoxide dismutase, catalase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase towards control. Histomorphometric analysis also supported biochemical findings of the study. The observations clearly demonstrated that baicalin treatment ameliorated Cd induced hepatic cytotoxicity and oxidative stress and provides evidence for its therapeutic potential against Cd induced oxidative stress.

Pharmacological intervention of tiferron and propolis to alleviate beryllium-induced hepatorenal toxicity

Intervention of chelating agent tiferron (sodium‐4,5‐dihydroxy‐1,3‐benzene disulfonate; 300 mg/kg, intraperitoneal) with propolis (honey beehive product; 200 mg/kg, p.o.) was evaluated to encounter the characteristic biochemical and ultra‐morphological alterations following subchronic exposure to beryllium. Female albino rats were challenged with beryllium nitrate (1 mg/kg, i.p.) daily for 28 days followed by treatment of the above‐mentioned therapeutic agents either individually or in combination for five consecutive days. Exposure to beryllium increased its concentration in the serum, liver and kidney, and caused significant alterations in cytochrome P450 activity, microsomal lipid peroxidation and proteins. Activities of alkaline phosphatase, lactate dehydrogenase, γ‐glutamyl transpeptidase, bilirubin, creatinine and urea in the serum and activity of acid phosphatase, alkaline phosphatase, adenosine triphosphatase, glucose‐6‐phophatase and succinic dehydrogenase in the liver and kidney were significantly altered after beryllium administration. Beryllium exposure also induced severe hepatorenal alterations at histopathological and ultra‐morphological level. Tiferron along with propolis dramatically reversed the alterations in all the variables more towards control rather than their individual treatment. The study concludes that pharmacological intervention of tiferron and propolis is beneficial in attenuating beryllium‐induced systemic toxicity.