Comparative role of acetaminophen, carbon tetrachloride and thioacetamide in development of fibrosis in rats.

Background: Several hepatotoxicants such as acetaminophen, carbon tetrachloride, and thioacetamide are repeatedly used to develop hepatic fibrosis to mimic the histological and hemodynamic characteristics of human illness. It may be a good idea to establish a better model among these hepatotoxicants to develop hepatic fibrosis. Aim: The present study evaluated comparative toxic effects of three model hepatotoxicants for experimental progression of fibrosis or cirrhosis. Materials and methods: Acetaminophen (200 mg/kg), carbon tetrachloride (200 µl/kg) and thioacetamide (200 mg/kg) were administered orally, thrice in a week for 8 weeks in different groups. After 8 weeks of exposure, animals were euthanized, blood and tissues were collected for various hematological, serological, tissue biochemical analysis and histological observations for comparative assessment of toxic consequences. Results: Significant deviation was noted in liver function tests, lipid peroxidation, glutathione, activities of superoxide dismutase, catalase, and GSH cycle enzymes; aniline hydroxylase, amidopyrine-N-demethylase, DNA fragmentation and level of hydroxyproline when compared with control group. Histology also depicted damage in liver histoarchitecture with exposure to acetaminophen, carbon tetrachloride and thioacetamide. Tukey's HSD post hoc test confirmed that thioacetamide produced severe toxic effects in comparison to carbon tetrachloride and acetaminophen. Conclusion: In conclusion, toxic effects were noted in ascending order as acetaminophen.

Quercetin ameliorates acute acrylamide induced spleen injury.

Acrylamide is used for industrial and laboratory purposes; it also is produced during cooking of carbohydrate-rich food at high temperature. We investigated the therapeutic potential of quercetin for treatment of acute acrylamide induced injury to the spleen. We used female albino rats treated with acrylamide for 10 days followed by oral administration of quercetin in three doses for 5 days. We observed significantly reduced total body weight, spleen weight, red blood cells, total proteins, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phophate dehydrogenase, reduced glutathione, concentration of serum IgG and IgM after acrylamide induced toxicity compared to controls. We also found that white blood cells, triglycerides, cholesterol and lipid oxidation were increased significantly after acrylamide induced toxicity in rats compared to controls. Histoarchitecture of spleen was affected adversely by acrylamide toxicity. Administration of quercetin ameliorated adverse effects of acrylamide in a dose-dependent manner. Quercetin appears to ameliorate acrylamide induced injury to the spleen by increasing endogenous antioxidants and improving histoarchitecture and immune function.

Naringenin protects hepato-renal tissues against antituberculosis drugs induced toxic manifestations by modulating interleukin-6, insulin like growth factor-1, biochemical and ultra-structural integrity.

BACKGROUND: The antituberculosis drugs (ATDs), isoniazid, rifampicin, pyrazinamide and ethambutol prompt extreme hepatic and renal damage during treatment of tuberculosis. The present study aimed to investigate protective potential of naringenin against ATDs induced hepato-renal injury. METHODS: Rats were administered with ATDs (pyrazinamide; 210, ethambutol; 170, isoniazid; 85, rifampicin; 65 mg/kg b.wt) orally for 8 weeks (3 days/week) followed by naringenin at three different doses (10, 20 and 40 mg/kg b.wt) conjointly for 8 weeks (3 days/week alternately to ATDs administration) and silymarin (50 mg/kg b.wt) as positive control. RESULTS: Exposure to ATDs caused significant increase in interleukin-6 (IL-6), triglycerides, cholesterol, bilirubin whereas depletion in insulin like growth factor-1 (IGF-1), albumin and glucose in serum. Endogenous antioxidant enzymes glutathione reductase (GR), glutathione peroxidase (GPx) and glucose-6-phosphate-dehydrogenase (G-6-PDH) were diminished in liver and kidney tissues with parallel increase in triglycerides, cholesterol, microsomal LPO and aniline hydroxylase (CYP2E1 enzyme). Ultra-structural observations of liver and kidney showed marked deviation in plasma membranes of various cellular and sub-cellular organelles after 8 weeks of exposure to ATDs. CONCLUSIONS: Conjoint treatment of naringenin counteracted ATDs induced toxic manifestations by regulating IL-6, IGF-1, CYP2E1, biochemical and ultra-structural integrity in a dose dependent manner. Naringenin has excellent potential to protect ATDs induced hepato-renal injury by altering oxidative stress, modulation of antioxidant enzymes, serum cytokines and ultra-structural changes.

Ameliorative impact of herbal formulation -Majoon-Dabeed-ul-ward and Sharbat-e-Deenar against CCl4 induced liver toxicity via regulation of antioxidant enzymes and oxidative stress.

Polyherbal Unani formulations have been used in the treatment of liver diseases for a long time. (Ibrahim M, Khaja MN, Aara A, Khan AA, Habeeb MA, Devi YP, Narasu ML, Habibullah CM. Hepatoprotective activity of Sapindus mukorossi and Rheum emodi extracts: in vitro and in vivo studies. World J Gastroenterol. 2008:14:2566-2571.) The aim of the present study was to investigate comparative hepatoprotective potential of Majoon-e-Dabeed-ul-ward (MD) and Sharbat-e-Deenar (SD) against CCl4 induced subchronic hepatic toxicity. In vivo study, albino rats were divided into 5 groups. Group I was control; Group II was experimental control treated with CCl4 (0.15 mL/kg, i.p. for 21 days); Groups III-IV treated with SD (2 mL/kg, p.o.) and MD (1,000 mg/kg, p.o.) for 5 days following CCl4 intoxication as in group 2 respectively; and Group V was positive control treated with silymarin (50 mg/kg, p.o.). In vitro hepatoprotective activity of SD and MD (25, 50, and 100 µg/mL) was assessed by SRB assay and flow cytometry analysis. CCl4 exposure significantly elevated the release of hepatic enzymes i.e. AST, ALT, LDH, and SALP in serum and lipid peroxidation in liver tissue which all these parameters were reversed after SD and MD administration. Therapy for 5 days also normalized the levels of antioxidant enzymes i.e. catalase, SOD, GPx, GR, tissue GSH, and aniline hydroxylase in CCl4 treated group. DNA damage and histological alterations caused by CCl4 were restored towards normal group. In vitro study showed protective effect of SD and MD against CCl4 treated HepG2 cell lines and rat hepatocytes. The results suggested that MD has a significant hepatoprotective potential and regulatory effect on oxidative stress than SD against CCl4 induced hepatotoxicity, and that this effect may be related to its antioxidant activity.

Protective activity of purpurin against d-galactosamine and lipopolysaccharide-induced hepatorenal injury by upregulation of heme oxygenase-1 in the RBC degradation cycle.

Acute liver failure, associated with oxidative stress and sustained inflammation is the major clinical manifestation of liver diseases with a high mortality rate due to limited therapeutic options. Purpurin is a bioactive compound of Rubia cordifolia that has been used in textile staining, as a food additive, and as a treatment of multiple chronic and metabolic diseases associated with inflammation and oxidative stress. The present work aimed to investigate the protective efficacy of purpurin against hepatorenal damage. Thirty-six female albino rats were equally assigned into six groups. Purpurin was administered orally once a day for 6 days at doses of 05, 10, and 20 mg/kg, respectively. Intraperitoneal injection of lipopolysaccharide (50 µg/kg) was administered to the animals on 6th day evening, 1 h after d-galactosamine (300 mg/kg) administration to induce hepatorenal injury. The results revealed that purpurin alleviated alterations in serological and hematological parameters as well as restored histoarchitectural and cellular integrity of the liver and kidney. Purpurin restored superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and glutathione content in hepatorenal tissues. Accompanied by the diminution of increased bilirubin and biliverdin, purpurin also diminished total cholesterol, triglyceride, and lipid peroxidation in hepatorenal tissues. Purpurin markedly attenuated the elevation of CYP2E1, restored glutathione-S-transferase, and prevented DNA damage in hepatorenal tissues. Purpurin reduced iron overload by reducing heme depletion and recycling of ferritin and hemosiderin. It also reinforced biliverdin reductase, heme oxygenase-1 to employ hepatorenal protection by regulating antioxidant enzymes and other pathways that produced NADPH. Thus, it may be concluded that purpurin has protective potential against acute hepatorenal injury.

Naringenin mitigates antituberculosis drugs induced hepatic and renal injury in rats.

Tuberculosis is one of the deadly diseases, which can be well treated by antituberculosis drugs (ATDs) i.e. isoniazid, rifampicin, pyrazinamide and ethambutol. These drugs also lead to severe hepatic and renal injury. The present study was designed to investigate efficacy of naringenin against ATDs induced hepato-renal injury. Rats were administered with ATDs for 8 weeks (3 day/week) followed by naringenin at three different doses (10, 20 and 40 mg/kg) conjointly for 8 weeks (3 days/week) orally. Silymarin (50 mg/kg) was used as positive control in the study. Hepatic and renal injury was measured by increased level of serological parameters such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, urea, uric acid and creatinine. The toxic effect of ATDs was also indicated by significant increase in lipid peroxidation along with decline in GSH, catalase and superoxide dismutase activity in liver and kidney tissues. Treatment with naringenin encountered ATDs induced injury as evident by significant reversal of biochemical indices towards their respective control in a dose dependent manner. Histopathological observations also supported biochemical findings. Assessment of TNF-α indicated therapeutic efficacy of naringenin at molecular level. Thus, results of this study clearly showed that naringenin possess protective role against ATDs induced hepato-renal injury and to take naringenin supplementation as food may be worthwhile to reduce ATDs induced hepato-renal injury.

Co-administration of adjuvants along with Moringa oleifera attenuates beryllium-induced oxidative stress and histopathological alterations in rats.

CONTEXT: Moringa oleifera Lam. (Moringaceae) is a rich source of antioxidants. All parts of the plant are medicinally important and have been used as traditional medicine for a variety of human ailments in India. OBJECTIVE: Therapeutic efficacy of adjuvants with M. oleifera (MO) root extract was investigated against beryllium-induced oxidative stress. MATERIALS AND METHODS: Hydroalcoholic (50% v/v) root extract of M. oleifera (150 mg/kg, p.o.) alone and combinations of M. oleifera with either piperine (2.5 mg/kg, p.o.) or curcumin (5.0 mg/kg, p.o.) daily for 1 week were administered in experimental rats against beryllium toxicity (1.0 mg/kg, i.p. daily for 5 weeks). Oxidative stress parameters including blood sugar, G-6-Pase in liver, and DNA damage were analyzed. Histopathological changes in liver and kidney were also observed. RESULTS: Beryllium enhanced lipid peroxidation (LPO), depleted reduced glutathione (GSH) and antioxidant enzymes activities, decreased blood sugar and G-6-Pase activity, and did not damage DNA. Histologically, liver was observed with structural loss and disintegration of hepatocytes, heavy vacuolation in hepatocytes, and kidney was observed with constriction of glomeruli and hypertrophy in epithelial cells of uriniferous tubules. Therapy of M. oleifera with piperine was effective; however, combination of M. oleifera with curcumin showed better therapeutic effect by reduction of LPO, elevated GSH level, maintained antioxidant enzymes activities, restored blood sugar, and G-6-Pase activity in liver together with almost normal histoarchitecture of liver and kidney. DISCUSSION AND CONCLUSION: Curcumin enhanced therapeutic efficacy of M. oleifera root extract and showed better antioxidant potential against beryllium toxicity.

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.

Role of micronutrients against dimethylmercury intoxication in male rats.

Mercury is one of the most toxic non-radioactive heavy metals. Chelation therapy has been the basis for the medical treatment of mercury poisoning. Male albino rats were administered dimethylmercury (1.5mg/kg) orally for 21 days. Chelation therapy with N-acetyl cysteine along with combination of antioxidants viz. zinc and selenium was given for 5 days after 24h of toxicant administration. All animals were sacrificed after 48h of last treatment and various blood biochemical parameters were performed. Toxicant caused rise in bilirubin, γ-GT, cholesterol, triglycerides, urea, creatinine, the uric acid content with a decline in albumin. A significant elevation was observed in LPO content and mercury concentration, along with concomitant decline in GSH levels after toxicant administration in liver, kidney and brain. Noticeable fall was also observed in AChE enzyme. Histopathological analysis was consistent with the biochemical observations and led to conclude that combination therapy provided protection against mercury toxicity.

Pyridoxine mitigates cadmium induced hepatic cytotoxicity and oxidative stress.

Therapeutic potential of pyridoxine (vit B6) was evaluated against cadmium induced hepatic cytotoxicity in culture and oxidative stress in rats. Nonmalignant "Chang" liver cell culture was exposed to Cd (cadmium chloride) that produced cytotoxicity in terms of increase in cell growth inhibition rate, alanine aminotransferase, lactate dehydrogenase and lipid peroxidation, which was significantly mitigated by pyridoxine in a concentration dependent manner. Acute exposure to Cd (6.5mg/kg body weight; ip once only) produced a condition of hepatic oxidative stress by substantially increasing lipid peroxidation and oxidized glutathione level along with corresponding decrease in reduced glutathione and various antioxidant enzymes, i.e., superoxide dismutase, catalase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase. Cadmium administration significantly increased the leakage of liver marker enzymes in serum, i.e., transaminases, alkaline phosphatase and lactate dehydrogenase. Therapy with pyridoxine after 3h of Cd administration decreased the release of serum transaminases, alkaline phosphatase and lactate dehydrogenase towards control. Administration of pyridoxine inhibited lipid peroxidation and formation of oxidized glutathione, increased the reduced glutathione level and restored the activities of aforesaid antioxidant enzymes towards control. The observations clearly demonstrated that pyridoxine treatment mitigates cadmium induced hepatic cytotoxicity and oxidative stress and provides evidence that it may be used clinically against Cd-induced hepatic toxicity.

Therapeutic influence of zinc and ascorbic acid against lead induced biochemical alterations.

The influence of co-administration of zinc (10 mg/kg, intraperitoneal [ip]) and ascorbic acid (10, 20 and 30 mg/kg, ip) against lead (lead acetate; 35 mg/kg, ip for 3 days) induced biochemical alterations was studied in young albino rats. The results revealed significant fall in hemoglobin content, on the other hand significant raise in the activity of serum transaminases and serum alkaline phosphatase after lead administration. Significant increase in lipid peroxidation and decreased level of reduced glutathione in liver showed oxidative stress due to lead exposure. Total protein content in liver and kidney were diminished after lead exposure. Activity of acid phosphatase in liver and kidney and alkaline phosphatase in kidney was increased significantly. Zinc and ascorbic acid treatment showed moderate therapeutic efficacy when administered individually, whereas more pronounced protective effects were observed after combined therapy of zinc and different doses of ascorbic acid. The results thus, suggested that co-administration of zinc and ascorbic acid may be useful in restoration of lead induced biochemical alterations.

Protective effects of propolis on inorganic mercury induced oxidative stress in mice.

Protective potential of propolis was evaluated against mercury induced oxidative stress and antioxidant enzymatic alterations in mice liver. Exposure to mercuric chloride (HgCl2; 5 mg/kg; ip) induced oxidative stress by increasing lipid peroxidation and oxidized glutathione level along with concomitant decrease in glutathione and various antioxidant enzymes. Mercury intoxication deviated the activity of liver marker enzymes in serum. Conjoint treatment of propolis (200 mg/kg; po) inhibited lipid peroxidation and oxidized glutathione level, whereas increased glutathione level. Activities of antioxidants enzymes, i.e., superoxide dismutase, catalase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase were also restored concomitantly towards control after propolis administration. Release of serum transaminases, alkaline phosphatase, lactate dehydrogenase and y-glutamyl transpeptidase were significantly restored towards control after propolis treatment. Results suggest that propolis augments the antioxidants defense against mercury induced toxicity and provides evidence that it has therapeutic potential as hepatoprotective agent.

Emodin reverses CCl induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural changes: The in vivo evidence.

AIM: The curative effect of emodin (1,3,8-trihydroxy-6-methyl anthraquinone), an active compound of the plant species Ventilago maderaspatana Gaertn, was evaluated against carbon tetrachloride (CCl(4)) induced hepatic cytochrome P450 (CYP) enzymatic and ultrastructural alterations in rats. METHODS: Female rats were administered CCl(4) (1.5 mL/kg, ip) followed by varying doses of emodin (20, 30 and 40 mg/kg, oral po) after 24 h of CCl(4) administration. Animals were euthanized after 24 h of last administration to determine liver function tests in serum, hepatic light microscopic and ultrastructural changes, activity of CYP enzymes, microsomal lipid peroxidation and protein contents, hexobarbitone induced sleep time and bromosulphalein retention. RESULTS: The CCl(4) induced-toxic effects were observed with sharp elevation in the release of serum transaminases, alkaline phosphatase, lactate dehydrogenase and gamma-glutamyl transpeptidase. An initial study for an optimum dose of emodin among different dose levels revealed that a 30 mg/kg dose was effective in restoring all the enzymatic variables and liver histoarchitecture in a dose dependent manner. Exposure to CCl(4) diminished the activities of CYP enzymes (i.e. aniline hydroxylase and amidopyrine-N-demethylase and microsomal protein contents with concomitant increase in microsomal lipid peroxidation). Emodin at 30 mg/kg effectively reversed the CCl(4) induced hepatotoxic events, which was consistent with ultrastructural observations. Hexobarbitone-induced sleep time and plasma bromosulphalein retention also improved liver functions after emodin therapy. CONCLUSION: By reversal CYP activity and ultrastructural changes, emodin shows a strong hepatoprotective abilities.

Resveratrol ameliorates carbon tetrachloride-induced acute liver injury in mice.

Present investigation aimed to evaluate the hepatoprotective potential of resveratrol (30mg/kg, po) in mice following two different routes (po and sc) of exposure to carbon tetrachloride (CCl(4), 1.0ml/kg). Administration of CCl(4) caused significant increase in the release of transaminases, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transpeptidase, creatinine kinase, total bilirubin, urea and uric acid in serum. Significantly enhanced hepatic lipid peroxidation and oxidized glutathione with marked depletion in reduced glutathione were observed after CCl(4) intoxication. It was also found that CCl(4) administration caused severe alterations in liver histology. Hepatic injury was more severe in those animals who received CCl(4) by oral route than those who exposed to CCl(4) subcutaneously. Resveratrol treatment was able to mitigate hepatic damage induced by acute intoxication of CCl(4) and showed pronounced curative effect against lipid peroxidation and deviated serum enzymatic variables as well as maintained glutathione status toward control. Treatment of resveratrol lessened CCl(4) induced damage in liver. The results of the present study suggest that resveratrol has potential to exert curative effects against liver injury.

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.

Reversal of effects of intra peritoneally administered beryllium nitrate by tiron and CaNa3DTPA alone or in combination with alpha-tocopherol.

To evaluate therapeutic efficacy of chelating agents tiron (Sodium-4,5-dihydroxy-1,3-benzene disulphonate) and CaNa3DTPA (Calcium trisodium diethylene triamine pentaacetic acid) in presence of alpha-tocopherol against beryllium induced toxicity, adult female albino rats were exposed to beryllium nitrate for 28 days followed by therapy with tiron (471 mg/kg, i.p.) and CaNa3DTPA (35 mg/kg, i.p.) alone and in combination with alpha-tocopherol (25 mg/kg, p.o.). Results revealed non-significant fall in haemoglobin and total serum protein content while significant fall in blood sugar level and activity of serum alkaline phosphatase. On the other hand, significant rise in the activity of serum transaminases and LDH was noticed after beryllium administration. Significant increase in total and esterified cholesterol was found in liver and kidney after toxicity. Significant increase in lipid peroxidation and decreased level of reduced glutathione in both the organs showed oxidative stress due to beryllium exposure. Histopathological and ultrastructural observations of liver and kidney revealed lesions due to beryllium toxicity followed by recovery due to combined therapy. CaNa3DTPA showed moderate therapeutic efficacy; however, its effectiveness was enhanced with alpha-tocopherol to some extent. Tiron in combination with alpha-tocopherol exerted statistically more beneficial effects in reversal of beryllium induced biochemical, histopathological and ultrastructural alterations.

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, gamma-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.

Synergistic effects of ferritin and propolis in modulation of beryllium induced toxicogenic alterations.

Synergistic therapeutic potential of ferritin (5mg/kg, i.p.) and propolis (honeybee hive product; 200mg/kg, p.o.) was analyzed to encounter the beryllium induced biochemical and ultra morphological alterations. Female albino rats were exposed to beryllium nitrate (1mg/kg, i.p.) daily for 28 days followed by treatment of above mentioned therapeutic agents either individually or in combination for five consecutive days. Exposure to beryllium increased its concentration in serum, liver and kidney and significantly altered the activities of CYP2E1 and CYP1A2 enzymes, microsomal lipid peroxidation and microsomal proteins. Activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transpeptidase, bilirubin, protein, creatinine and urea in serum as well as hemoglobin and blood glucose level; activity of acid phosphatase, alkaline phosphatase, adenosine triphosphatase, glucose-6-phosphatase and succinic dehydrogenase, total triglycerides, total cholesterol, total protein contents, glycogen contents, lipid peroxidation and glutathione level in liver and kidney were significantly altered after beryllium administration. Beryllium exposure severely altered ultramorphology of liver and kidney that proved its toxic consequences at cellular level. Ferritin in combination with propolis dramatically reversed the alterations of these variables towards control in a synergistic manner concluding its beneficial effects over monotherapy in attenuating beryllium induced systemic toxicity.

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.

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.